

@article{Veronesi2024,
title = {(±)‐Catechins inhibit prehaustorium formation in the parasitic weed &lt;scp&gt;\textit{Phelipanche ramosa}&lt;/scp&gt; and reduce tomato infestation},
author = {Christophe Veronesi and Estelle Billard and Philippe Delavault and Philippe Simier},
doi = {10.1002/ps.8472},
issn = {1526-4998},
year  = {2025},
date = {2025-02-01},
urldate = {2025-02-01},
journal = {Pest Management Science},
publisher = {Wiley},
abstract = {&lt;jats:title&gt;Abstract&lt;/jats:title&gt;&lt;jats:sec&gt;&lt;jats:title&gt;BACKGROUND&lt;/jats:title&gt;&lt;jats:p&gt;&lt;jats:italic&gt;Phelipanche ramosa&lt;/jats:italic&gt; L. (Pomel) is a noxious parasitic weed in field and vegetable crops in Mediterranean countries. Control of this pest is complex and far from being achieved, and new environmentally‐friendly strategies are being sought. The present study evaluates the possibility of using (±)‐catechins as a natural herbicide against broomrapes.&lt;/jats:p&gt;&lt;/jats:sec&gt;&lt;jats:sec&gt;&lt;jats:title&gt;RESULTS&lt;/jats:title&gt;&lt;jats:p&gt;The results show that (±)‐catechins have no effect on GR24‐induced germination over a wide concentration range (10&lt;jats:sup&gt;−4&lt;/jats:sup&gt; to 10&lt;jats:sup&gt;−10&lt;/jats:sup&gt; &lt;jats:sc&gt;m&lt;/jats:sc&gt;), nor on radicle elongation after germination, but strongly inhibit, at 10&lt;jats:sup&gt;−4&lt;/jats:sup&gt; and 10&lt;jats:sup&gt;−5&lt;/jats:sup&gt; &lt;jats:sc&gt;m&lt;/jats:sc&gt;, prehaustorium formation in response to the haustorium‐inducing factor, &lt;jats:italic&gt;cis/trans&lt;/jats:italic&gt;‐zeatin. Accordingly, pot experiments involving the supplies of 10&lt;jats:sup&gt;−5&lt;/jats:sup&gt; &lt;jats:sc&gt;m&lt;/jats:sc&gt; of (±)‐catechins to tomato plants infested or not with &lt;jats:italic&gt;P&lt;/jats:italic&gt;. &lt;jats:italic&gt;ramosa&lt;/jats:italic&gt; demonstrate that (±)‐catechins do not influence growth of non‐parasitized tomato plants and prevent heavy infestation by strongly reducing parasite attachments and inducing parasite necrosis once they are attached.&lt;/jats:p&gt;&lt;/jats:sec&gt;&lt;jats:sec&gt;&lt;jats:title&gt;CONCLUSION&lt;/jats:title&gt;&lt;jats:p&gt;This study points the potential use of (±)‐catechins for parasitic weed control. It raises also the question of the mechanisms involved in the inhibition of prehaustorium formation and the necrosis of parasite attachments in response to (±)‐catechins application. © 2024 The Author(s). &lt;jats:italic&gt;Pest Management Science&lt;/jats:italic&gt; published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.&lt;/jats:p&gt;&lt;/jats:sec&gt;},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@techreport{nokey,
title = {Comprehensive protocol for preparing diatom cell samples and associated bacterial consortia for scanning electron microscopy},
author = {Margaux Maillard and Nicolas Stephant and Astsuko Tanaka and Leila Tirichine},
editor = {Elsevier },
url = {https://www.sciencedirect.com/science/article/pii/S2666166724005458?via%3Dihub},
doi = {https://doi.org/10.1016/j.xpro.2024.103380},
year  = {2024},
date = {2024-12-20},
urldate = {2024-12-20},
journal = {STAR Protocols},
volume = {5},
number = {103380},
issue = {4},
abstract = {Meticulous sample preparation and strict adherence to preservation procedures are essential for electron microscopy investigations, which enable accurate capture of organisms’ morphology, size, and potential interactions within the sample. Here, we present a protocol for preserving cells of the model diatom Phaeodactylum tricornutum and its native bacterial community. We describe steps for diatom fixation and coverslip preparation and washing. We then detail procedures for dehydrating, drying, and metallizing samples followed by observation using scanning electron microscopy.
},
keywords = {team 5},
pubstate = {published},
tppubtype = {techreport}
}
@article{Young2024,
title = {CIRCUS: CIRCUlating tumour cells in soft tissue Sarcoma - a short report},
author = {Robin J. Young and Joanna E. Chowdry and Denis Cochonneau and Dominique Heymann},
doi = {10.20517/cdr.2024.149},
issn = {2578-532X},
year  = {2024},
date = {2024-12-13},
urldate = {2024-12-13},
journal = {Cancer Drug Resist},
publisher = {OAE Publishing Inc.},
abstract = {Aims:  Circulating tumour cells (CTCs) can be detected in peripheral blood using their physical properties (increased size and less deformable than normal circulating blood cells) or using cell surface markers. The study of these CTCs should provide important insights into tumour biology, including mechanisms of drug resistance. We performed a pilot study (IRAS ID: 235459) to evaluate if CTCs could be isolated from peripheral blood samples collected from soft tissue sarcoma (STS) patients.
Methods:  We used a combined approach that first enriched samples for CTCs using a microfluidic cassette via ParosrtixTMPR1, and then sorted cells stained for vimentin and cytokeratin using the DEPArrayTM. The total circulating cell-free DNA (cfDNA) level was also analysed. Data were correlated with clinical parameters.
Results:  13 patients were recruited to this study: 7 patients with localised disease and 6 patients with metastatic disease. CTCs exhibited a high heterogeneity based on their expression of mesenchymal and epithelial biomarkers. There was no significant difference in the number of CTCs between patients with localised versus metastatic disease. We observed no correlation between CTC numbers and cfDNA; however, the number of CTCs did correlate with primary tumour size.
Conclusion:  The present study demonstrates the presence of CTCs in STS patients with localised and advanced disease. Further and larger studies are needed to characterise STS CTCs and to evaluate their prognostic significance.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@online{nokey,
title = {  Complete genome sequence of a marine Pseudoalteromonas bacterial strain},
author = {Eric Manirakiza and Timothée Chaumier and Leila Tirichine},
editor = {ASM Journals},
url = {https://journals.asm.org/doi/10.1128/mra.00975-24?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed},
doi = {10.1128/mra.00975-24},
isbn = {39655917},
year  = {2024},
date = {2024-12-10},
journal = {Microbiol Resour Announc .},
pages = {e0097524},
abstract = {Pseudoalteromonas is an abundant bacterial genera, found ubiquitously, including in extreme environments. Its broad metabolic capacity enables unique associations with various organisms. Using PacBio sequencing, we generated the complete genome sequence of a marine Pseudoalteromonas, revealing two circular chromosomes and one putative plasmid. The genome data are accessible at https://BacBrowse.univ-nantes.fr.},
keywords = {marine bacteria, team 5},
pubstate = {published},
tppubtype = {online}
}
@article{Oliver2024,
title = {Transcriptional landscape of the interaction of human Mesenchymal Stem Cells with Glioblastoma in bioprinted co-cultures},
author = {Lisa Oliver and Yuna Landais and Catherine Gratas and Pierre-François Cartron and François Paris and Dominique Heymann and François M. Vallette and Aurelien Serandour},
doi = {10.1186/s13287-024-04022-6},
issn = {1757-6512},
year  = {2024},
date = {2024-12-00},
urldate = {2024-12-00},
journal = {Stem Cell Res Ther},
volume = {15},
number = {1},
publisher = {Springer Science and Business Media LLC},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{nokey,
title = {Evolutionary genomics of the emergence of brown algae as key components of coastal ecosystems},
author = {France Denoeud and Olivier Godfroy and Corinne Cruaud and Svenja Heesch and Zofia Nehr and Nachida Tadrent and Arnaud Couloux and Loraine Brillet-Guéguen and Ludovic Delage and Dean Mckeown and Taizo Motomura and Duncan Sussfeld and Xiao Fan 0and Lisa Mazéas and Nicolas Terrapon and Josué Barrera-Redondo and Romy Petroll and Lauric Reynes and Seok-Wan Choi and Jihoon Jo and Kavitha Uthanumallian and Kenny Bogaert and Céline Duc and Pélagie Ratchinski and Agnieszka Lipinska and Benjamin Noel and Eleanor A Murphy and Martin Lohr 0and Ananya Khatei and Pauline Hamon-Giraud and Christophe Vieira and Komlan Avia and Svea Sanja Akerfors 0and Shingo Akita and Yacine Badis and Tristan Barbeyron and Arnaud Belcour and Wahiba Berrabah and Samuel Blanquart and Ahlem Bouguerba-Collin and Trevor Bringloe and Rose Ann Cattolico and Alexandre Cormier and Helena Cruz de Carvalho and Romain Dallet and Olivier De Clerck and Ahmed Debit and Erwan Denis and Christophe Destombe and Erica Dinatale and Simon Dittami and Elodie Drula and Sylvain Faugeron 0and Jeanne Got and Louis Graf and Agnès Groisillier and Marie-Laure Guillemin and Lars Harms and William John Hatchett and Bernard Henrissat and Galice Hoarau and Chloé Jollivet and Alexander Jueterbock and Ehsan Kayal and Andrew H Knoll and Kazuhiro Kogame and Arthur Le Bars and Catherine Leblanc and Line Le Gall and Ronja Ley 0and Xi Liu and Steven T LoDuca and Pascal Jean Lopez 0and Philippe Lopez and Eric Manirakiza and Karine Massau and Stéphane Mauger and Laetitia Mest and Gurvan Michel and Catia Monteiro and Chikako Nagasato and Delphine Nègre and Eric Pelletier and Naomi Phillips and Philippe Potin and Stefan A Rensing and Ellyn Rousselot and Sylvie Rousvoal and Declan Schroeder and Delphine Scornet and Anne Siegel and Leila Tirichine and Thierry Tonon and Klaus Valentin and Heroen Verbruggen and Florian Weinberger and Glen Wheeler and Hiroshi Kawai and Akira F Peters and Hwan Su Yoon and Cécile Hervé 0and Naihao Ye and Eric Bapteste and Myriam Valero and Gabriel V Markov and Erwan Corre and Susana M Coelho and Patrick Wincker and Jean-Marc Aury and J Mark Cock },
editor = {Cell Press},
url = {https://www.cell.com/cell/fulltext/S0092-8674(24)01272-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867424012728%3Fshowall%3Dtrue},
doi = {doi: 10.1016/j.cell.2024.10.049},
year  = {2024},
date = {2024-11-27},
journal = {Cell},
volume = {187},
issue = {24},
pages = {6943-6965},
abstract = {Brown seaweeds are keystone species of coastal ecosystems, often forming extensive underwater forests, and are under considerable threat from climate change. In this study, analysis of multiple genomes has provided insights across the entire evolutionary history of this lineage, from initial emergence, through later diversification of the brown algal orders, down to microevolutionary events at the genus level. Emergence of the brown algal lineage was associated with a marked gain of new orthologous gene families, enhanced protein domain rearrangement, increased horizontal gene transfer events, and the acquisition of novel signaling molecules and key metabolic pathways, the latter notably related to biosynthesis of the alginate-based extracellular matrix, and halogen and phlorotannin biosynthesis. We show that brown algal genome diversification is tightly linked to phenotypic divergence, including changes in life cycle strategy and zoid flagellar structure. The study also showed that integration of large viral genomes has had a significant impact on brown algal genome content throughout the emergence of the lineage.},
keywords = {Algae, team 5},
pubstate = {published},
tppubtype = {article}
}
@article{Martinez2024,
title = {Comparative Analysis of Two Neighboring Conducive and Suppressive Soils Toward Plant Parasitism Caused by \textit{Phelipanche ramosa} on \textit{Brassica napus}},
author = {Lisa Martinez and Jean-Bernard Pouvreau and Christophe Jestin and Gregory Montiel and Antoine Gravot and Solenne Berardocco and Nathalie Marnet and Alain Bouchereau and Erwan Delage and Philippe Simier and Lucie Poulin},
doi = {10.1094/pbiomes-12-23-0140-r},
issn = {2471-2906},
year  = {2024},
date = {2024-11-00},
urldate = {2024-11-00},
journal = {Phytobiomes Journal},
volume = {8},
number = {4},
pages = {425--445},
publisher = {Scientific Societies},
abstract = {&lt;jats:p&gt; In Western France, rapeseed ( Brassica napus) cultivation faces substantial yield losses due to the root holoparasitic plant Phelipanche ramosa. However, recent observations have shown a reduction in parasitism within previously heavily infested fields. This study investigates two neighboring rapeseed soils with distinct levels of parasitic infestation, considered suppressive and conducive. Using a cocultivation system of Brassica napus and P. ramosa, we comprehensively examined rhizosphere exudates, parasitic plant attachment, and rhizosphere soil microbiota. Our findings revealed that the suppressive soil effectively reduced parasitism by impeding broomrape attachment and development, as well as inducing necrosis of tubercles. This suppressive effect was specific to postattachment stages, leaving germination and haustoriogenesis preattachment stages unaffected. Analysis of microbial structures suggested that the suppression of parasitism is predominantly of fungal rather than bacterial origin. Correlation network analyses identified three groups of amplicon sequence variants (ASVs) associated with suppression. Notably, seven ASVs were inversely correlated with parasitic attachments, and only one ASV, identified as Berkeleyomyces, a necrotrophic fungus responsible for black root rot, was positively correlated with necrosis and was more abundant in the suppressive soil. This study demonstrates the contrasting parasitic plant development on two physicochemically similar soils, highlighting the central role of fungal dynamics in the rhizosphere. These results provide valuable insights into the mechanisms underlying soil-mediated suppression of P. ramosa, offering potential strategies for mitigating the impact of this root holoparasite on rapeseed yields in the region. &lt;/jats:p&gt;},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Veronesi2024b,
title = {(±)‐Catechins inhibit prehaustorium formation in the parasitic weed &lt;scp&gt;\textit{Phelipanche ramosa}&lt;/scp&gt; and reduce tomato infestation},
author = {Christophe Veronesi and Estelle Billard and Philippe Delavault and Philippe Simier},
doi = {10.1002/ps.8472},
issn = {1526-4998},
year  = {2024},
date = {2024-10-05},
urldate = {2024-10-05},
journal = {Pest Management Science},
publisher = {Wiley},
abstract = {&lt;jats:title&gt;Abstract&lt;/jats:title&gt;&lt;jats:sec&gt;&lt;jats:title&gt;BACKGROUND&lt;/jats:title&gt;&lt;jats:p&gt;&lt;jats:italic&gt;Phelipanche ramosa&lt;/jats:italic&gt; L. (Pomel) is a noxious parasitic weed in field and vegetable crops in Mediterranean countries. Control of this pest is complex and far from being achieved, and new environmentally‐friendly strategies are being sought. The present study evaluates the possibility of using (±)‐catechins as a natural herbicide against broomrapes.&lt;/jats:p&gt;&lt;/jats:sec&gt;&lt;jats:sec&gt;&lt;jats:title&gt;RESULTS&lt;/jats:title&gt;&lt;jats:p&gt;The results show that (±)‐catechins have no effect on GR24‐induced germination over a wide concentration range (10&lt;jats:sup&gt;−4&lt;/jats:sup&gt; to 10&lt;jats:sup&gt;−10&lt;/jats:sup&gt; &lt;jats:sc&gt;m&lt;/jats:sc&gt;), nor on radicle elongation after germination, but strongly inhibit, at 10&lt;jats:sup&gt;−4&lt;/jats:sup&gt; and 10&lt;jats:sup&gt;−5&lt;/jats:sup&gt; &lt;jats:sc&gt;m&lt;/jats:sc&gt;, prehaustorium formation in response to the haustorium‐inducing factor, &lt;jats:italic&gt;cis/trans&lt;/jats:italic&gt;‐zeatin. Accordingly, pot experiments involving the supplies of 10&lt;jats:sup&gt;−5&lt;/jats:sup&gt; &lt;jats:sc&gt;m&lt;/jats:sc&gt; of (±)‐catechins to tomato plants infested or not with &lt;jats:italic&gt;P&lt;/jats:italic&gt;. &lt;jats:italic&gt;ramosa&lt;/jats:italic&gt; demonstrate that (±)‐catechins do not influence growth of non‐parasitized tomato plants and prevent heavy infestation by strongly reducing parasite attachments and inducing parasite necrosis once they are attached.&lt;/jats:p&gt;&lt;/jats:sec&gt;&lt;jats:sec&gt;&lt;jats:title&gt;CONCLUSION&lt;/jats:title&gt;&lt;jats:p&gt;This study points the potential use of (±)‐catechins for parasitic weed control. It raises also the question of the mechanisms involved in the inhibition of prehaustorium formation and the necrosis of parasite attachments in response to (±)‐catechins application. © 2024 The Author(s). &lt;jats:italic&gt;Pest Management Science&lt;/jats:italic&gt; published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.&lt;/jats:p&gt;&lt;/jats:sec&gt;},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{nokey,
title = {Genomic sequences and annotations of two Pseudomonas species isolated from marine and terrestrial habitats},
author = {Eric Manirakiza and Timothée Chaumier and Leïla Tirichine},
editor = {ASM Journals},
doi = { https://doi.org/10.1128/mra.00373-24},
year  = {2024},
date = {2024-08-27},
urldate = {2024-08-27},
journal = {Microbiol Resour Announc .},
pages = {e0037324},
abstract = {Here, we present the complete genome sequences and annotations of two species of the Pseudomonas genus isolated from marine and terrestrial environments. Both genomes and their annotations are available on BacBrowse (https://BacBrowse.univ-nantes.fr). This study will contribute to a better understanding of the diversity present within the Pseudomonas genus.},
keywords = {marine bacteria, team 5},
pubstate = {published},
tppubtype = {article}
}
@article{Grandjean2024,
title = {Pectin Remodeling and Involvement of AtPME3 in the Parasitic Plant–Plant Interaction, Phelipanche ramosa–Arabidospis thaliana},
author = {Cyril Grandjean and Christophe Veronesi and Christine Rusterucci and Charlotte Gautier and Yannis Maillot and Maïté Leschevin and Françoise Fournet and Jan Drouaud and Paulo Marcelo and Luciane Zabijak and Philippe Delavault and Philippe Simier and Sophie Bouton and Karine Pageau},
doi = {10.3390/plants13152168},
issn = {2223-7747},
year  = {2024},
date = {2024-08-00},
journal = {Plants},
volume = {13},
number = {15},
publisher = {MDPI AG},
abstract = {<jats:p>Phelipanche ramosa is a root parasitic plant fully dependent on host plants for nutrition and development. Upon germination, the parasitic seedling develops inside the infected roots a specific organ, the haustorium, thanks to the cell wall-degrading enzymes of haustorial intrusive cells, and induces modifications in the host’s cell walls. The model plant Arabidopsis thaliana is susceptible to P. ramosa; thus, mutants in cell wall metabolism, particularly those involved in pectin remodeling, like Atpme3-1, are of interest in studying the involvement of cell wall-degrading enzymes in the establishment of plant–plant interactions. Host–parasite co-cultures in mini-rhizotron systems revealed that parasite attachments are twice as numerous and tubercle growth is quicker on Atpme3-1 roots than on WT roots. Compared to WT, the increased susceptibility in AtPME3-1 is associated with reduced PME activity in the roots and a lower degree of pectin methylesterification at the host–parasite interface, as detected immunohistochemically in infected roots. In addition, both WT and Atpme3-1 roots responded to infestation by modulating the expression of PAE- and PME-encoding genes, as well as related global enzyme activities in the roots before and after parasite attachment. However, these modulations differed between WT and Atpme3-1, which may contribute to different pectin remodeling in the roots and contrasting susceptibility to P. ramosa. With this integrative study, we aim to define a model of cell wall response to this specific biotic stress and indicate, for the first time, the role of PME3 in this parasitic plant–plant interaction.</jats:p>},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
@article{Grandjean2024b,
title = {Pectin Remodeling and Involvement of AtPME3 in the Parasitic Plant–Plant Interaction, Phelipanche ramosa–Arabidospis thaliana},
author = {Cyril Grandjean and Christophe Veronesi and Christine Rusterucci and Charlotte Gautier and Yannis Maillot and Maïté Leschevin and Françoise Fournet and Jan Drouaud and Paulo Marcelo and Luciane Zabijak and Philippe Delavault and Philippe Simier and Sophie Bouton and Karine Pageau},
doi = {10.3390/plants13152168},
issn = {2223-7747},
year  = {2024},
date = {2024-08-00},
journal = {Plants},
volume = {13},
number = {15},
publisher = {MDPI AG},
abstract = {<jats:p>Phelipanche ramosa is a root parasitic plant fully dependent on host plants for nutrition and development. Upon germination, the parasitic seedling develops inside the infected roots a specific organ, the haustorium, thanks to the cell wall-degrading enzymes of haustorial intrusive cells, and induces modifications in the host’s cell walls. The model plant Arabidopsis thaliana is susceptible to P. ramosa; thus, mutants in cell wall metabolism, particularly those involved in pectin remodeling, like Atpme3-1, are of interest in studying the involvement of cell wall-degrading enzymes in the establishment of plant–plant interactions. Host–parasite co-cultures in mini-rhizotron systems revealed that parasite attachments are twice as numerous and tubercle growth is quicker on Atpme3-1 roots than on WT roots. Compared to WT, the increased susceptibility in AtPME3-1 is associated with reduced PME activity in the roots and a lower degree of pectin methylesterification at the host–parasite interface, as detected immunohistochemically in infected roots. In addition, both WT and Atpme3-1 roots responded to infestation by modulating the expression of PAE- and PME-encoding genes, as well as related global enzyme activities in the roots before and after parasite attachment. However, these modulations differed between WT and Atpme3-1, which may contribute to different pectin remodeling in the roots and contrasting susceptibility to P. ramosa. With this integrative study, we aim to define a model of cell wall response to this specific biotic stress and indicate, for the first time, the role of PME3 in this parasitic plant–plant interaction.</jats:p>},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
@article{Grandjean2024c,
title = {Pectin Remodeling and Involvement of AtPME3 in the Parasitic Plant–Plant Interaction, Phelipanche ramosa–Arabidospis thaliana},
author = {Cyril Grandjean and Christophe Veronesi and Christine Rusterucci and Charlotte Gautier and Yannis Maillot and Maïté Leschevin and Françoise Fournet and Jan Drouaud and Paulo Marcelo and Luciane Zabijak and Philippe Delavault and Philippe Simier and Sophie Bouton and Karine Pageau},
doi = {10.3390/plants13152168},
issn = {2223-7747},
year  = {2024},
date = {2024-08-00},
journal = {Plants},
volume = {13},
number = {15},
publisher = {MDPI AG},
abstract = {<jats:p>Phelipanche ramosa is a root parasitic plant fully dependent on host plants for nutrition and development. Upon germination, the parasitic seedling develops inside the infected roots a specific organ, the haustorium, thanks to the cell wall-degrading enzymes of haustorial intrusive cells, and induces modifications in the host’s cell walls. The model plant Arabidopsis thaliana is susceptible to P. ramosa; thus, mutants in cell wall metabolism, particularly those involved in pectin remodeling, like Atpme3-1, are of interest in studying the involvement of cell wall-degrading enzymes in the establishment of plant–plant interactions. Host–parasite co-cultures in mini-rhizotron systems revealed that parasite attachments are twice as numerous and tubercle growth is quicker on Atpme3-1 roots than on WT roots. Compared to WT, the increased susceptibility in AtPME3-1 is associated with reduced PME activity in the roots and a lower degree of pectin methylesterification at the host–parasite interface, as detected immunohistochemically in infected roots. In addition, both WT and Atpme3-1 roots responded to infestation by modulating the expression of PAE- and PME-encoding genes, as well as related global enzyme activities in the roots before and after parasite attachment. However, these modulations differed between WT and Atpme3-1, which may contribute to different pectin remodeling in the roots and contrasting susceptibility to P. ramosa. With this integrative study, we aim to define a model of cell wall response to this specific biotic stress and indicate, for the first time, the role of PME3 in this parasitic plant–plant interaction.</jats:p>},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
@article{Grandjean2024d,
title = {Pectin Remodeling and Involvement of AtPME3 in the Parasitic Plant–Plant Interaction, Phelipanche ramosa–Arabidospis thaliana},
author = {Cyril Grandjean and Christophe Veronesi and Christine Rusterucci and Charlotte Gautier and Yannis Maillot and Maïté Leschevin and Françoise Fournet and Jan Drouaud and Paulo Marcelo and Luciane Zabijak and Philippe Delavault and Philippe Simier and Sophie Bouton and Karine Pageau},
doi = {10.3390/plants13152168},
issn = {2223-7747},
year  = {2024},
date = {2024-08-00},
urldate = {2024-08-00},
journal = {Plants},
volume = {13},
number = {15},
publisher = {MDPI AG},
abstract = {&lt;jats:p&gt;Phelipanche ramosa is a root parasitic plant fully dependent on host plants for nutrition and development. Upon germination, the parasitic seedling develops inside the infected roots a specific organ, the haustorium, thanks to the cell wall-degrading enzymes of haustorial intrusive cells, and induces modifications in the host’s cell walls. The model plant Arabidopsis thaliana is susceptible to P. ramosa; thus, mutants in cell wall metabolism, particularly those involved in pectin remodeling, like Atpme3-1, are of interest in studying the involvement of cell wall-degrading enzymes in the establishment of plant–plant interactions. Host–parasite co-cultures in mini-rhizotron systems revealed that parasite attachments are twice as numerous and tubercle growth is quicker on Atpme3-1 roots than on WT roots. Compared to WT, the increased susceptibility in AtPME3-1 is associated with reduced PME activity in the roots and a lower degree of pectin methylesterification at the host–parasite interface, as detected immunohistochemically in infected roots. In addition, both WT and Atpme3-1 roots responded to infestation by modulating the expression of PAE- and PME-encoding genes, as well as related global enzyme activities in the roots before and after parasite attachment. However, these modulations differed between WT and Atpme3-1, which may contribute to different pectin remodeling in the roots and contrasting susceptibility to P. ramosa. With this integrative study, we aim to define a model of cell wall response to this specific biotic stress and indicate, for the first time, the role of PME3 in this parasitic plant–plant interaction.&lt;/jats:p&gt;},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{nokey,
title = {H3K27me3 and EZH Are Involved in the Control of the Heat-Stress-Elicited Morphological Changes in Diatoms},
author = {Mhammad Zarif and Ellyn Rousselot and Bruno Jesus and Leïla Tirichine and Céline Duc},
editor = {MDPI},
url = {https://www.mdpi.com/1422-0067/25/15/8373},
doi = {doi.org/10.3390/ijms25158373},
year  = {2024},
date = {2024-07-31},
journal = {Int. J. Mol. Sci.},
volume = {25},
issue = {15},
pages = {8373},
abstract = {Marine water temperatures are increasing due to anthropogenic climate change, constituting a major threat to marine ecosystems. Diatoms are major marine primary producers, and as such, they are subjected to marine heat waves and rising ocean temperatures. Additionally, under low tide, diatoms are regularly exposed to high temperatures. However, physiological and epigenetic responses to long-term exposure to heat stress remain largely unknown in the diatom Phaeodactylum tricornutum. In this study, we investigated changes in cell morphology, photosynthesis, and H3K27me3 abundance (an epigenetic mark consisting of the tri-methylation of lysine 27 on histone H3) after moderate and elevated heat stresses. Mutants impaired in PtEZH—the enzyme depositing H3K27me3—presented reduced growth and moderate changes in their PSII quantum capacities. We observed shape changes for the three morphotypes of P. tricornutum (fusiform, oval, and triradiate) in response to heat stress. These changes were found to be under the control of PtEZH. Additionally, both moderate and elevated heat stresses modulated the expression of genes encoding proteins involved in photosynthesis. Finally, heat stress elicited a reduction of genome-wide H3K27me3 levels in the various morphotypes. Hence, we provided direct evidence of epigenetic control of the H3K27me3 mark in the responses of Phaeodactylum tricornutum to heat stress.},
keywords = {epigenetics, EZH, Phaeodactylum tricornutum, Post-translational modification, team 5},
pubstate = {published},
tppubtype = {article}
}
@article{pmid38938184,
title = {Multivalent inhibition of the  fumigatus KDNase},
author = {Mathieu Scalabrini and Denis Loquet and Camille Rochard and Mélyne Baudin Marie and Coralie Assailly and Yoan Brissonnet and Franck Daligault and Amélie Saumonneau and Annie Lambert and Cyrille Grandjean and David Deniaud and Paul Lottin and Sagrario Pascual and Laurent Fontaine and Viviane Balloy and Sébastien G Gouin},
doi = {10.1039/d4ob00601a},
issn = {1477-0539},
year  = {2024},
date = {2024-07-01},
urldate = {2024-07-01},
journal = {Org Biomol Chem},
volume = {22},
number = {28},
pages = {5783--5789},
abstract = { is a saprophytic fungus and opportunistic pathogen often causing fatal infections in immunocompromised patients. Recently KDNAse, an exoglycosidase hydrolyzing 3-deoxy-D-galacto-D--nonulosonic acid (KDN), a rare sugar from the sialic acid family, was identified and characterized. The principal function of KDNAse is still unclear, but a study suggests a critical role in fungal cell wall morphology and virulence. Potent KDNAse inhibitors are required to better probe the enzyme&#039;s biological role and as potential antivirulence factors. In this work, we developed a set of KDNAse inhibitors based on enzymatically stable thio-KDN motifs. C2, C9-linked heterodi-KDN were designed to fit into unusually close KDN sugar binding pockets in the protein. A polymeric compound with an average of 54 KDN motifs was also designed by click chemistry. Inhibitory assays performed on recombinant KDNAse showed a moderate and strong enzymatic inhibition for the two classes of compounds, respectively. The poly-KDN showed more than a nine hundred fold improved inhibitory activity (IC = 1.52 ± 0.37 μM, 17-fold in a KDN molar basis) compared to a monovalent KDN reference, and is to our knowledge, the best synthetic inhibitor described for a KDNase. Multivalency appears to be a relevant strategy for the design of potent KDNase inhibitors. Importantly, poly-KDN was shown to strongly decrease filamentation when co-cultured with  at micromolar concentrations, opening interesting perspectives in the development of antivirulence factors.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{pmid38529534,
title = {Structure Revision of a Widespread Marine Sulfonolipid Class Based on Isolation and Total Synthesis},
author = {Dávid Roman and Philippe Meisinger and Richard Guillonneau and Chia-Chi Peng and Lukas K Peltner and Paul M Jordan and Veit Haensch and Sebastian Götze and Oliver Werz and Christian Hertweck and Yin Chen and Christine Beemelmanns},
url = { hal-04587238v1 },
doi = {10.1002/anie.202401195},
issn = {1521-3773},
year  = {2024},
date = {2024-06-01},
urldate = {2024-06-01},
journal = {Angew Chem Int Ed Engl},
volume = {63},
number = {23},
pages = {e202401195},
abstract = {The cosmopolitan marine Roseobacter clade is of global biogeochemical importance. Members of this clade produce sulfur-containing amino lipids (SALs) involved in biofilm formation and marine surface colonization processes. Despite their physiological relevance and abundance, SALs have only been explored through genomic mining approaches and lipidomic studies based on mass spectrometry, which left the relative and absolute structures of SALs unresolved, hindering progress in biochemical and functional investigations. Herein, we report the structural revision of a new group of SALs, which we named cysteinolides, using a combination of analytical techniques, isolation and degradation experiments and total synthetic efforts. Contrary to the previously proposed homotaurine-based structures, cysteinolides are composed of an N,O-acylated cysteinolic acid-containing head group carrying various different (α-hydroxy)carboxylic acids. We also performed the first validated targeted-network based analysis, which allowed us to map the distribution and structural diversity of cysteinolides across bacterial lineages. Beyond offering structural insight, our research provides SAL standards and validated analytical data. This information holds significance for forthcoming investigations into bacterial sulfonolipid metabolism and biogeochemical nutrient cycling within marine environments.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{cordova_why_2024,
title = {Why are osteoporosis patients treated with antiresorptive therapies considered like oncology patients regarding their oral health care?},
author = {Luis A. Cordova and David González-Quintanilla and Dominique Heymann},
url = {https://doi.org/10.1007/s00198-024-07173-7},
doi = {10.1007/s00198-024-07173-7},
issn = {1433-2965},
year  = {2024},
date = {2024-06-01},
urldate = {2024-06-01},
journal = {Osteoporosis International},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{pmid38547578b,
title = {A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma},
author = {Verónica Rey and Juan Tornín and Juan Jose Alba-Linares and Cristina Robledo and Dzohara Murillo and Aida Rodríguez and Borja Gallego and Carmen Huergo and Cristina Viera and Alejandro Braña and Aurora Astudillo and Dominique Heymann and Karoly Szuhai and Judith V M G Bovée and Agustín F Fernández and Mario F Fraga and Javier Alonso and René Rodríguez},
url = {inserm-04524777v1 },
doi = {10.1016/j.ebiom.2024.105090},
issn = {2352-3964},
year  = {2024},
date = {2024-04-01},
urldate = {2024-04-01},
journal = {EBioMedicine},
volume = {102},
pages = {105090},
abstract = {BACKGROUND: Sarcomas represent an extensive group of malignant diseases affecting mesodermal tissues. Among sarcomas, the clinical management of chondrosarcomas remains a complex challenge, as high-grade tumours do not respond to current therapies. Mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes are among the most common mutations detected in chondrosarcomas and may represent a therapeutic opportunity. The presence of mutated IDH (mIDH) enzymes results in the accumulation of the oncometabolite 2-HG leading to molecular alterations that contribute to drive tumour growth.

METHODS: We developed a personalized medicine strategy based on the targeted NGS/Sanger sequencing of sarcoma samples (n = 6) and the use of matched patient-derived cell lines as a drug-testing platform. The anti-tumour potential of IDH mutations found in two chondrosarcoma cases was analysed in vitro, in vivo and molecularly (transcriptomic and DNA methylation analyses).

FINDINGS: We treated several chondrosarcoma models with specific mIDH1/2 inhibitors. Among these treatments, only the mIDH2 inhibitor enasidenib was able to decrease 2-HG levels and efficiently reduce the viability of mIDH2 chondrosarcoma cells. Importantly, oral administration of enasidenib in xenografted mice resulted in a complete abrogation of tumour growth. Enasidenib induced a profound remodelling of the transcriptomic landscape not associated to changes in the 5 mC methylation levels and its anti-tumour effects were associated with the repression of proliferative pathways such as those controlled by E2F factors.

INTERPRETATION: Overall, this work provides preclinical evidence for the use of enasidenib to treat mIDH2 chondrosarcomas.

FUNDING: Supported by the Spanish Research Agency/FEDER (grants PID2022-142020OB-I00; PID2019-106666RB-I00), the ISC III/FEDER (PI20CIII/00020; DTS18CIII/00005; CB16/12/00390; CB06/07/1009; CB19/07/00057); the GEIS group (GEIS-62); and the PCTI (Asturias)/FEDER (IDI/2021/000027).},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{pmid38518627,
title = {Methodology for small animals targeted irradiations at conventional and ultra-high dose rates 65 MeV proton beam},
author = {Manon Evin and Charbel Koumeir and Arthur Bongrand and Gregory Delpon and Ferid Haddad and Quentin Mouchard and Vincent Potiron and Gaëlle Saade and Noël Servagent and Daphnée Villoing and Vincent Métivier and Sophie Chiavassa},
url = { hal-04556782v1 },
doi = {10.1016/j.ejmp.2024.103332},
issn = {1724-191X},
year  = {2024},
date = {2024-04-01},
urldate = {2024-04-01},
journal = {Phys Med},
volume = {120},
pages = {103332},
abstract = {As part of translational research projects, mice may be irradiated on radiobiology platforms such as the one at the ARRONAX cyclotron. Generally, these platforms do not feature an integrated imaging system. Moreover, in the context of ultra-high dose-rate radiotherapy (FLASH-RT), treatment planning should consider potential changes in the beam characteristics and internal movements in the animal. A patient-like set-up and methodology has been implemented to ensure target coverage during conformal irradiations of the brain, lungs and intestines. In addition, respiratory cycle amplitudes were quantified by fluoroscopic acquisitions on a mouse, to ensure organ coverage and to assess the impact of respiration during FLASH-RT using the 4D digital phantom MOBY. Furthermore, beam incidence direction was studied from mice µCBCT and Monte Carlo simulations. Finally,in vivodosimetry with dose-rate independent radiochromic films (OC-1) and their LET dependency were investigated. The immobilization system ensures that the animal is held in a safe and suitable position. The geometrical evaluation of organ coverage, after the addition of the margins around the organs, was satisfactory. Moreover, no measured differences were found between CONV and FLASH beams enabling a single model of the beamline for all planning studies. Finally, the LET-dependency of the OC-1 film was determined and experimentally verified with phantoms, as well as the feasibility of using these filmsin vivoto validate the targeting. The methodology developed ensures accurate and reproducible preclinical irradiations in CONV and FLASH-RT without in-room image guidance in terms of positioning, dose calculation andin vivodosimetry.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1128/spectrum.04091-23,
title = {Development and utilization of new O_{2}-independent bioreporters},
author = {Eva Agranier and Pauline Crétin and Aurélie Joublin-Delavat and Léa Veillard and Katia Touahri and François Delavat},
url = {https://journals.asm.org/doi/abs/10.1128/spectrum.04091-23
hal-04505221v1 },
doi = {10.1128/spectrum.04091-23},
year  = {2024},
date = {2024-03-05},
urldate = {2024-03-05},
journal = {Microbiology Spectrum},
volume = {0},
number = {0},
pages = {e04091-23},
abstract = {Fluorescent proteins are used for decades, and have allowed major discoveries in biology in a wide variety of fields, and are used in environmental as well as clinical contexts. Green fluorescent protein (GFP) and all its derivatives share a common feature: they rely on the presence of dioxygen (O2) for protein maturation and fluorescence. This dependency precludes their use in anoxic environments. Here, we constructed a series of genetic circuits allowing production of KOFP-7, an O2-independant flavin-binding fluorescent protein. We demonstrated that Escherichia coli cells producing KOFP-7 are fluorescent, both at the population and single-cell levels. Importantly, we showed that, unlike cells producing GFP, cells producing KOFP-7 are fluorescent in anoxia. Finally, we demonstrated that Vibrio diazotrophicus NS1, a facultative anaerobe, is fluorescent in the absence of O2 when KOFP-7 is produced. Altogether, the development of new genetic circuits allowing O2-independent fluorescence will open new perspective to study anaerobic processes.},
keywords = {EDIPHIS, SMIDIDI, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{nokey,
title = {microRNA-encoded peptides inhibit seed germination of the root parasitic plant Orobanche cumana},
author = {Sabine Tourneur, Jean-Philippe Combier, Serge Plaza, Stéphane Muños, Philippe Delavault},
url = {hal-04578646v1 },
doi = { https://doi.org/10.1002/ppp3.10501},
year  = {2024},
date = {2024-02-19},
urldate = {2024-02-19},
journal = {New Phytologist},
abstract = {Societal Impact Statement

The root parasitic plant Orobanche cumana (sunflower broomrape) is one of the major pests of sunflower crops. Despite intense efforts to develop effective agricultural practices and breeding programs, selective control of broomrapes is still rare and ineffective in terms of sustainability. It is thus essential to develop new specific control methods against those pests. miRNA-encoded peptides (miPEPs) are a new class of peptides regulating the expression of miRNAs and their corresponding target genes. This study demonstrates that certain miPEPs strongly inhibit the germination of broomrape seeds by regulating their miR gene, making them good candidates for use as biocontrol agents against this pathogen.
Summary

    Root parasitic plants of the Orobanchaceae family are a constant and growing threat to agriculture worldwide. Among them, the parasitic weed Orobanche cumana, the sunflower broomrape, causes significant losses to sunflower production in European-Asian and North African countries. Despite the use of several conventional control methods against this pathogen, none has proved effective or durable, underlining the need to develop innovative strategies. miRNA-encoded peptides (miPEPs) are regulatory peptides stimulating the expression of their own primary transcript of miRNA, and plant watering with those molecules leads to down-regulating specifically miRNA target genes and altering plant physiology.
    Through seed germination assays and qRT-PCR analysis, we investigated the impact of exogenous treatments of synthetic miPEPs on broomrape seed germination.
    First, we report that the conserved miRNA repertoire of O. cumana consists of 39 members. Thirty-nine miPEPs were designed, synthetized, and assayed, 11 of which strongly inhibited O. cumana seed germination. Interestingly, miPEP319a showed the strongest inhibiting effect while miPEP319b did not. Three out of the four corresponding miR319 target genes showed upregulation after treatment with a germination stimulant, which was impaired by treatment with miPEP319a. This downregulation of expression is associated with an increase in the expression of the corresponding pri-miR319a.
    We reveal thus that the use of miPEPs can increase our knowledge of key molecular mechanisms underlying a complex parasite interaction and should provide a new phytosanitary method to control broomrape parasitism with highly specific and biodegradable natural substances.

},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{pmid38311823,
title = {Preclinical toxicological assessment of polydatin in zebrafish model},
author = {Lucia Emanueli Schimith and Vitória Machado da Silva and Dennis Guilherme da Costa-Silva and Linda Karolynne Seregni Monteiro and Ana Luiza Muccillo-Baisch and Corinne André-Miral and Mariana Appel Hort},
url = {https://hal.science/hal-04610793v1},
doi = {10.1080/01480545.2024.2311287},
issn = {1525-6014},
year  = {2024},
date = {2024-02-01},
urldate = {2024-02-01},
journal = {Drug Chem Toxicol},
pages = {1--10},
abstract = {Polydatin (3,4&#039;,5-trihydroxystilbene-3-β-D-glucoside, piceid), a natural stilbenoid found in different plant sources, has gained increasing attention for its potential health benefits. However, prior to its widespread adoption in human therapeutics and consumer products, a comprehensive investigation of its toxicological effects is crucial. In this study, the toxicity of polydatin was investigated in a developmental toxicity test using zebrafish () as a valuable model for preclinical assessments. We employed the Fish Embryo Test (FET test - OECD n°236) to investigate the effects of polydatin on survival, hatchability, development, and behavior of zebrafish embryo-larval stage. Remarkably, the results demonstrated that polydatin up to 435 μM showed no toxicity. Throughout the exposure period, zebrafish embryos exposed to polydatin exhibited normal development, with no significant mortality observed. Furthermore, hatching success and heartbeat rate were unaffected, and no morphological abnormalities were identified, signifying a lack of teratogenic effects and cardiotoxicity. Locomotion activity assessment revealed normal swimming patterns and response to stimuli, indicating no neurotoxic effects. Our study provides valuable insights into the toxicological profile of polydatin, suggesting that it may offer potential therapeutic benefits under a considerable concentration range. In addition, zebrafish model proves to be an efficient system for early-stage toxicological screening, guiding further investigations into the secure utilization of polydatin for human health and wellness.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{Timothée2024,
title = {Genome-wide assessment of genetic diversity and transcript variations in 17 accessions of the model diatom Phaeodactylum tricornutum},
author = {Chaumier Timothée and Feng Yang and Eric Manirakiza and Ouardia Ait-Mohamed and Yue Wu and Udita Chandola and Bruno Jesus and Gwenael Piganeau and Agnès Groisillier and Leila Tirichine},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10833087/},
doi = {10.1093/ismeco/ycad008},
year  = {2024},
date = {2024-01-10},
urldate = {2024-01-10},
journal = {ISME Communications},
volume = {4},
issue = {1},
pages = {ycad008},
abstract = {Diatoms, a prominent group of phytoplankton, have a significant impact on both the oceanic food chain and carbon sequestration, thereby playing a crucial role in regulating the climate. These highly diverse organisms show a wide geographic distribution across various latitudes. In addition to their ecological significance, diatoms represent a vital source of bioactive compounds that are widely used in biotechnology applications. In the present study, we investigated the genetic and transcriptomic diversity of 17 accessions of the model diatom Phaeodactylum tricornutum including those sampled a century ago as well as more recently collected accessions. The analysis of the data reveals a higher genetic diversity and the emergence of novel clades, indicating an increasing diversity within the P. tricornutum population structure, compared to the previous study and a persistent long-term balancing selection of genes in old and newly sampled accessions. However, the study did not establish a clear link between the year of sampling and genetic diversity, thereby, rejecting the hypothesis of loss of heterozygoty in cultured strains. Transcript analysis identified novel transcript including noncoding RNA and other categories of small RNA such as PiwiRNAs. Additionally, transcripts analysis using differential expression as well as Weighted Gene Correlation Network Analysis has provided evidence that the suppression or downregulation of genes cannot be solely attributed to loss-of-function mutations. This implies that other contributing factors, such as epigenetic modifications, may play a crucial role in regulating gene expression. Our study provides novel genetic resources, which are now accessible through the platform PhaeoEpiview (https://PhaeoEpiView.univ-nantes.fr), that offer both ease of use and advanced tools to further investigate microalgae biology and ecology, consequently enriching our current understanding of these organisms.},
keywords = {epigenetics, microalgae, team 5},
pubstate = {published},
tppubtype = {article}
}
@article{Goux2023.04.11.536264,
title = {Sucrose phosphorylase from Alteromonas mediterranea: structural insight into the regioselective α-glucosylation of (+)-catechin},
author = {Marine Goux and Marie Demonceaux and Johann Hendrickx and Claude Solleux and Emilie Lormeau and Folmer Fredslund and David Tezé and Bernard Offmann and Corinne André-Miral},
url = {https://www.biorxiv.org/content/10.1101/2023.04.11.536264v2
hal-04095395v2 },
doi = {10.1016/j.biochi.2024.01.004},
year  = {2024},
date = {2024-01-09},
urldate = {2024-01-09},
journal = {Biochimie},
publisher = {Cold Spring Harbor Laboratory},
abstract = {Sucrose phosphorylases, through transglycosylation reactions, are interesting enzymes that can transfer regioselectively glucose from sucrose, the donor substrate, onto acceptors like flavonoids to form glycoconjugates and hence modulate their solubility and bioactivity. Here, we report for the first time the structure of sucrose phosphorylase from the marine bacteria Alteromonas mediterranea (AmSP) and its enzymatic properties. Kinetics of sucrose hydrolysis and transglucosylation capacities on (+)-catechin were investigated. Wild-type enzyme (AmSP-WT) displayed high hydrolytic activity on sucrose and was devoid of transglucosylation activity on (+)-catechin. Two variants, AmSP-Q353F and AmSP-P140D catalysed the regiospecific transglucosylation of (+)-catechin: 89 % of a novel compound (+)-catechin-4′-O-α-d-glucopyranoside (CAT-4′) for AmSP-P140D and 92 % of (+)-catechin-3′-O-α-d-glucopyranoside (CAT-3′) for AmSP-Q353F. The compound CAT-4′ was fully characterized by NMR and mass spectrometry. An explanation for this difference in regiospecificity was provided at atomic level by molecular docking simulations: AmSP-P140D was found to preferentially bind (+)-catechin in a mode that favours glucosylation on its hydroxyl group in position 4′ while the binding mode in AmSP-Q353F favoured glucosylation on its hydroxyl group in position 3’.},
keywords = {Funregiox, team 1, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{bios14010043,
title = {Photonic Crystal Surface Mode Real-Time Imaging of RAD51 DNA Repair Protein Interaction with the ssDNA Substrate},
author = {Galina Nifontova and Cathy Charlier and Nizar Ayadi and Fabrice Fleury and Alexander Karaulov and Alyona Sukhanova and Igor Nabiev},
url = {https://www.mdpi.com/2079-6374/14/1/43
hal-04449485v1 },
doi = {10.3390/bios14010043},
issn = {2079-6374},
year  = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Biosensors},
volume = {14},
number = {1},
abstract = {Photonic crystals (PCs) are promising tools for label-free sensing in drug discovery screening, diagnostics, and analysis of ligand-receptor interactions. Imaging of PC surface modes has emerged as a novel approach to the detection of multiple binding events at the sensor surface. PC surface modification and decoration with recognition units yield an interface providing the highly sensitive detection of cancer biomarkers, antibodies, and oligonucleotides. The RAD51 protein plays a central role in DNA repair via the homologous recombination pathway. This recombinase is essential for the genome stability and its overexpression is often correlated with aggressive cancer. RAD51 is therefore a potential target in the therapeutic strategy for cancer. Here, we report the designing of a PC-based array sensor for real-time monitoring of oligonucleotide-RAD51 recruitment by means of surface mode imaging and validation of the concept of this approach. Our data demonstrate that the designed biosensor ensures the highly sensitive multiplexed analysis of association-dissociation events and detection of the biomarker of DNA damage using a microfluidic PC array. The obtained results highlight the potential of the developed technique for testing the functionality of candidate drugs, discovering new molecular targets and drug entities. This paves the way to further adaption and bioanalytical use of the biosensor for high-content screening to identify new DNA repair inhibitor drugs targeting the RAD51 nucleoprotein filament or to discover new molecular targets.},
keywords = {impact, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{JUBELIN2024119660,
title = {Identification of MCM4 and PRKDC as new regulators of osteosarcoma cell dormancy based on 3D cell cultures},
author = {Camille Jubelin and Javier Muñoz-Garcia and Emilie Ollivier and Denis Cochonneau and François Vallette and Marie-Françoise Heymann and Lisa Oliver and Dominique Heymann},
url = {https://www.sciencedirect.com/science/article/pii/S016748892400003X
 inserm-04501791v1 },
doi = {https://doi.org/10.1016/j.bbamcr.2024.119660},
issn = {0167-4889},
year  = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Biochimica et Biophysica Acta (BBA) - Molecular Cell Research},
pages = {119660},
abstract = {Dormancy is a potential way for tumors to develop drug resistance and escape treatment. However, the mechanisms involved in cancer dormancy remain poorly understood. This is mainly because there is no in vitro culture model making it possible to spontaneously induce dormancy. In this context, the present work proposes the use of three-dimensional (3D) spheroids developed from osteosarcoma cell lines as a relevant model for studying cancer dormancy. MNNG-HOS, SaOS-2, 143B, MG-63, U2OS and SJSA-1 cell lines were cultured in 3D using the Liquid Overlay Technique (LOT). Dormancy was studied by staining cancer cells with a lipophilic dye (DiD), and long-term DiD+ cells were considered as dormant cancer cells. The role of the extracellular matrix in inducing dormancy was investigated by embedding cells into methylcellulose or Geltrex™. Gene expression of DiD+ cells was assessed with a Nanostring™ approach and the role of the genes detected in dormancy was validated by a transient down-expression model using siRNA treatment. Proliferation was measured using fluorescence microscopy and the xCELLigence technology. We observed that MNNG-HOS, 143B and MG-G3 cell lines had a reduced proliferation rate in 3D compared to 2D. U2OS cells had an increased proliferation rate when they were cultured in Geltrex™ compared to other 3D culture methods. Using 3D cultures, a transcriptomic signature of dormancy was obtained and showed a decreased expression of 18 genes including ETV4, HELLS, ITGA6, MCM4, PRKDC, RAD21 and UBE2T. The treatment with siRNA targeting these genes showed that cancer cell proliferation was reduced when the expression of ETV4 and MCM4 were decreased, whereas proliferation was increased when the expression of RAD21 was decreased. 3D culture facilitates the maintenance of dormant cancer cells characterized by a reduced proliferation and less differential gene expression as compared to proliferative cells. Further studies of the genes involved has enabled us to envisage their role in regulating cell proliferation.},
keywords = {3D spheroids, Cell dormancy, Osteosarcoma, Quiescency, team 3, Transcriptomic profile},
pubstate = {published},
tppubtype = {article}
}
@article{microorganisms12010186,
title = {Genetic Insights into Biofilm Formation by a Pathogenic Strain of Vibrio harveyi},
author = {Amandine Morot and François Delavat and Alexis Bazire and Christine Paillard and Alain Dufour and Sophie Rodrigues},
url = {https://www.mdpi.com/2076-2607/12/1/186
hal-04406039v1 },
doi = {10.3390/microorganisms12010186},
issn = {2076-2607},
year  = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Microorganisms},
volume = {12},
number = {1},
abstract = {The Vibrio genus includes bacteria widely distributed in aquatic habitats and the infections caused by these bacteria can affect a wide range of hosts. They are able to adhere to numerous surfaces, which can result in biofilm formation that helps maintain them in the environment. The involvement of the biofilm lifestyle in the virulence of Vibrio pathogens of aquatic organisms remains to be investigated. Vibrio harveyi ORM4 is a pathogen responsible for an outbreak in European abalone Haliotis tuberculata populations. In the present study, we used a dynamic biofilm culture technique coupled with laser scanning microscopy to characterize the biofilm formed by V. harveyi ORM4. We furthermore used RNA-seq analysis to examine the global changes in gene expression in biofilm cells compared to planktonic bacteria, and to identify biofilm- and virulence-related genes showing altered expression. A total of 1565 genes were differentially expressed, including genes associated with motility, polysaccharide synthesis, and quorum sensing. The up-regulation of 18 genes associated with the synthesis of the type III secretion system suggests that this virulence factor is induced in V. harveyi ORM4 biofilms, providing indirect evidence of a relationship between biofilm and virulence.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{ijms25073633,
title = {Human Rad51 Protein Requires Higher Concentrations of Calcium Ions for D-Loop Formation than for Oligonucleotide Strand Exchange},
author = {Axelle Renodon-Corniere and Tsutomu Mikawa and Naoyuki Kuwabara and Kentaro Ito and Dmitri Levitsky and Hiroshi Iwasaki and Masayuki Takahashi},
url = {https://www.mdpi.com/1422-0067/25/7/3633},
doi = {10.3390/ijms25073633},
issn = {1422-0067},
year  = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {International Journal of Molecular Sciences},
volume = {25},
number = {7},
abstract = {Human Rad51 protein (HsRad51)-promoted DNA strand exchange, a crucial step in homologous recombination, is regulated by proteins and calcium ions. Both the activator protein Swi5/Sfr1 and Ca2+ ions stimulate different reaction steps and induce perpendicular DNA base alignment in the presynaptic complex. To investigate the role of base orientation in the strand exchange reaction, we examined the Ca2+ concentration dependence of strand exchange activities and structural changes in the presynaptic complex. Our results show that optimal D-loop formation (strand exchange with closed circular DNA) required Ca2+ concentrations greater than 5 mM, whereas 1 mM Ca2+ was sufficient for strand exchange between two oligonucleotides. Structural changes indicated by increased fluorescence intensity of poly(dεA) (a poly(dA) analog) reached a plateau at 1 mM Ca2+. Ca2+ &gt; 2 mM was required for saturation of linear dichroism signal intensity at 260 nm, associated with rigid perpendicular DNA base orientation, suggesting a correlation with the stimulation of D-loop formation. Therefore, Ca2+ exerts two different effects. Thermal stability measurements suggest that HsRad51 binds two Ca2+ ions with KD values of 0.2 and 2.5 mM, implying that one step is stimulated by one Ca2+ bond and the other by two Ca2+ bonds. Our results indicate parallels between the Mg2+ activation of RecA and the Ca2+ activation of HsRad51.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{cancers16132351,
title = {A Prospective Observational Cohort Study for Newly Diagnosed Osteosarcoma Patients in the UK: ICONIC Study Initial Results},
author = {Alexa Childs and Craig Gerrand and Bernadette Brennan and Robin Young and Kenneth S. Rankin and Michael Parry and Jonathan Stevenson and Adrienne M. Flanagan and Rachel M. Taylor and Lorna Fern and Dominique Heymann and Filipa Vance and Jenny Sherriff and Saurabh Singh and Rubina Begum and Sharon L. Forsyth and Krystyna Reczko and Kate Sparksman and William Wilson and Sandra J. Strauss},
url = {https://www.mdpi.com/2072-6694/16/13/2351},
doi = {10.3390/cancers16132351},
issn = {2072-6694},
year  = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Cancers},
volume = {16},
number = {13},
abstract = {There has been little change to the standard treatment for osteosarcoma (OS) over the last 25 years and there is an unmet need to identify new biomarkers and novel therapeutic approaches if outcomes are to improve. Furthermore, there is limited evidence on the impact of OS treatment on patient-reported outcomes (PROs). ICONIC (Improving Outcomes through Collaboration in Osteosarcoma; NCT04132895) is a prospective observational cohort study recruiting newly diagnosed OS patients across the United Kingdom (UK) with matched longitudinal collection of clinical, biological, and PRO data. During Stage 1, which assessed the feasibility of recruitment and data collection, 102 patients were recruited at 22 sites with representation from patient groups frequently excluded in OS studies, including patients over 50 years and those with less common primary sites. The feasibility of collecting clinical and biological samples, in addition to PRO data, has been established and there is ongoing analysis of these data as part of Stage 2. ICONIC will provide a unique, prospective cohort of newly diagnosed OS patients representative of the UK patient population, with fully annotated clinical outcomes linked to molecularly characterised biospecimens, allowing for comprehensive analyses to better understand biology and develop new biomarkers and novel therapeutic approaches.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{pmid37853951,
title = {Normal B cells express ZAP70 in chronic lymphocytic leukemia: A link between autoimmunity and lymphoproliferation?},
author = {Dana Ghergus and Mickaël Martin and Anne-Marie Knapp and Fabien Delmotte and Aurélie Joublin-Delavat and Sophie Jung and Jean-Nicolas Schickel and Isabelle Mendel and Arnaud Dupuis and Bernard Drénou and Hervé Ghesquières and Gilles Salles and Lucile Baseggio and Raoul Herbrecht and Anne-Sophie Korganow and Laurent Vallat and Pauline Soulas-Sprauel and Eric Meffre and Thierry Martin},
url = {https://hal.science/hal-04343628v1},
doi = {10.1002/ajh.27137},
issn = {1096-8652},
year  = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Am J Hematol},
volume = {99},
number = {1},
pages = {48--56},
abstract = {ZAP70 has a prognostic value in chronic lymphocytic leukemia (CLL), through altered B-cell receptor signaling, which is important in CLL pathogenesis. A good correlation between ZAP70 expression in CLL cells and the occurrence of autoimmune phenomena has been reported. Yet, the great majority of CLL-associated autoimmune cytopenia is due to polyclonal immunoglobulin (Ig) G synthesized by nonmalignant B cells, and this phenomenon is poorly understood. Here, we show, using flow cytometry, that a substantial percentage of CD5- nonmalignant B cells from CLL patients expresses ZAP70 compared with CD5- B cells from healthy subjects. This ZAP70 expression in normal B cells from CLL patients was also evidenced by the detection of ZAP70 mRNA at single-cell level with polyclonal Ig heavy- and light-chain gene transcripts. ZAP70+ normal B cells belong to various B-cell subsets and their presence in the naïve B-cell subset suggests that ZAP70 expression may occur during early B-cell development in CLL patients and potentially before malignant transformation. The presence of ZAP70+ normal B cells is associated with autoimmune cytopenia in CLL patients in our cohort of patients, and recombinant antibodies produced from these ZAP70+ nonmalignant B cells were frequently autoreactive including anti-platelet reactivity. These results provide a better understanding of the implication of ZAP70 in CLL leukemogenesis and the mechanisms of autoimmune complications of CLL.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{GRATON2024114608,
title = {Antioxidant properties of catechin and its 3′O-α-glucoside: Insights from computational chemistry calculations},
author = {Jérôme Graton and Anaïs Goupille and Tanguy Ferré and Bernard Offmann and Corinne André-Miral and Jean-Yves Le Questel},
url = {https://www.sciencedirect.com/science/article/pii/S2210271X24001476
https://hal.science/hal-04610796v1},
doi = {https://doi.org/10.1016/j.comptc.2024.114608},
issn = {2210-271X},
year  = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Computational and Theoretical Chemistry},
volume = {1236},
pages = {114608},
abstract = {Density functional theory (DFT) calculations were used to investigate the conformational landscape of catechin and one of its main glucoside derivative (catechin-3′ O- α −glucopyranoside), and to determine the corresponding antioxidant properties. These investigations were carried out in benzene and water using the SMD universal continuum solvation model. Both properties were found to be significantly affected. The structures are characterized in both solvents by strong intramolecular hydrogen bonds (IMHB). In an apolar environment, Hydrogen Atom Transfer (HAT) is by far favored whereas in water the Sequential Proton Loss Electron Transfer (SPLET) mechanism is strongly preferred. In benzene, the catechin fragment has the best antioxidant character (from 27 kJ/mole) whereas in polar surroundings, the glucoside derivative has a slightly better antiradical activity (from 5 kJ/mole). Our results confirm the key role of the 3′-OH and 4′-OH groups of the catechole ring in these properties.},
keywords = {Antioxidant properties, Catechin, catechin-3′O- α-glucoside, Conformations, Density Functional Theory, Implicit solvent effects, team 1, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{panez-toro_roles_2023,
title = {Roles of inflammatory cell infiltrate in periprosthetic osteolysis},
author = {Isidora Panez-Toro and Dominique Heymann and François Gouin and Jérôme Amiaud and Marie-Françoise Heymann and Luis A. Córdova},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2023.1310262/full
 inserm-04501796v1 },
doi = {10.3389/fimmu.2023.1310262},
issn = {1664-3224},
year  = {2023},
date = {2023-12-01},
urldate = {2023-12-01},
journal = {Frontiers in Immunology},
volume = {14},
pages = {1310262},
abstract = {Classically, particle-induced periprosthetic osteolysis at the implant–bone interface has explained the aseptic loosening of joint replacement. This response is preceded by triggering both the innate and acquired immune response with subsequent activation of osteoclasts, the bone-resorbing cells. Although particle-induced periprosthetic osteolysis has been considered a foreign body chronic inflammation mediated by myelomonocytic-derived cells, current reports describe wide heterogeneous inflammatory cells infiltrating the periprosthetic tissues. This review aims to discuss the role of those non-myelomonocytic cells in periprosthetic tissues exposed to wear particles by showing original data. Specifically, we discuss the role of T cells (CD3+ 
, CD4+, and CD8+) and B cells (CD20+) coexisting with CD68+/TRAP−multinucleated giant cells associated with both polyethylene and metallic particles infiltrating retrieved periprosthetic membranes. This review contributes valuable insight to support the complex cell and molecular mechanisms behind the aseptic loosening theories of orthopedic implants.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{nokey,
title = {Photonic Crystal Surface Mode Imaging for Multiplexed Real-Time Detection of Antibodies, Oligonucleotides, and DNA Repair Proteins},
author = { Galina Nifontova, Evgeniia Gerasimovich, Fabrice Fleury, Alyona Sukhanova, Igor Nabiev },
url = {hal-04363661v1 },
doi = {https://doi.org/10.1051/epjconf/202328703007 },
year  = {2023},
date = {2023-10-13},
journal = {EPJ Web of Conferences},
volume = {287},
abstract = {Abstract. Sensors based on photonic crystal (PC) surface mode imaging are promising tools for
label-free drug screening and discovery, diagnostics, and analysis of ligand–receptor interactions.
Imaging of PC surface modes has been demonstrated to allow simultaneous real-time detection of
multiple events at the sensor surface. Here, we report the engineering of a lateral-flow microfluidic
assay where PC surface mode imaging is used for multiplexed detection of biomolecular targets
(antibodies, oligonucleotides, and a DNA repair protein), as well as kinetic data on their interactions
obtained without additional labelling or signal amplification. Our data demonstrate the suitability of
the biosensing platform designed for ultrasensitive, quick, and low-cost detection and monitoring of
interactions between different biomolecules},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@conference{nokey,
title = {Dosimetric environment of preclinical FLASH hadrontherapy studies at the ARRONAX cyclotron},
author = { Manon Evin , Charbel Koumeir , Quentin Mouchard , Grégory Delpon , Ferid Haddad , Vincent Potiron , Gaëlle Saade , Mathieu Chocry , Noël Servagent , Stéphane Supiot , Vincent Métivier , Sophie Chiavassa },
url = {hal-04245917v1 },
year  = {2023},
date = {2023-10-10},
urldate = {2023-10-10},
keywords = {team 3},
pubstate = {published},
tppubtype = {conference}
}
@conference{nokey,
title = {Dosimetric environment and first results of the studies on the physicochemical and biological mechanisms of FLASH hadrontherapy at the ARRONAX cyclotron},
author = {Manon Evin, Charbel Koumeir , Quentin Mouchard , Guillaume Blain , Craff Emeline , Grégory Delpon , Vincent Fiegel , Giovanna Rosa Fois, Youssef Ghannam , Ferid Haddad , Lydia Maigne , Vincent Potiron, Gaëlle Saade , Noël Servagent , Stéphane Supiot (3) , Sarra Terfas , Johan Vandenborre , Vincent Métivier , Sophie Chiavassa },
url = { hal-04249398v1 },
year  = {2023},
date = {2023-10-04},
urldate = {2023-10-04},
keywords = {team 3},
pubstate = {published},
tppubtype = {conference}
}
@article{dubois_high_2023,
title = {High glucose exposure drives intestinal barrier dysfunction by altering its morphological, structural and functional properties.},
author = {Nolwenn Dubois and Javier Muñoz-Garcia and Dominique Heymann and Axelle Renodon-Cornière},
url = {hal-04210189v1 },
doi = {10.1016/j.bcp.2023.115765},
issn = {1873-2968 0006-2952},
year  = {2023},
date = {2023-10-01},
urldate = {2023-10-01},
journal = {Biochemical pharmacology},
volume = {216},
pages = {115765},
abstract = {High dietary glucose consumption and hyperglycemia can result in chronic complications. Several studies suggest that high glucose (HG) induces dysfunction of the intestinal barrier. However, the precise changes remain unclear. In our study, we used in vitro models composed of Caco-2 and/or HT29-MTX cells in both monoculture and co-culture to assess the effects of long-term HG exposure on the morphological, structural, and functional properties of the intestinal barrier. Cells were grown in medium containing normal physiologic glucose (NG, 5.5 mM) or a clinically relevant HG (25 mM) concentration until 21 days. Results demonstrated that HG induced morphological changes, with the layers appearing denser and less organized than under physiological conditions, which is in accordance with the increased migration capacity of Caco-2 cells and proliferation properties of HT29-MTX cells. Although we mostly observed a small decrease in mRNA and protein expressions of three junction proteins (ZO-1, OCLN and E-cad) in both Caco-2 and HT29-MTX cells cultured in HG medium, confocal microscopy showed that HG induced a remarkable reduction in their immunofluorescence intensity, triggering disruption of their associated structural network. In addition, we highlighted that HG affected different functionalities (permeability, mucus production and alkaline phosphatase activity) of monolayers with Caco-2 and HT29-MTX cells. Interestingly, these alterations were stronger in co-culture than in monoculture, suggesting a cross-relationship between enterocytes and goblet cells. Controlling hyperglycemia remains a major therapeutical method for reducing damage to the intestinal barrier and improving therapies.},
note = {Place: England},
keywords = {Colorectal cancer, High glucose, In vitro models, Intercellular junction proteins, Intestinal barrier function, Intestinal epithelium, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{pmid37516363,
title = {First evidence of in vivo effect of FLASH radiotherapy with helium ions in zebrafish embryos},
author = {Youssef Ghannam and Sophie Chiavassa and Gaëlle Saade and Charbel Koumeir and Guillaume Blain and Grégory Delpon and Manon Evin and Ferid Haddad and Lydia Maigne and Quentin Mouchard and Noël Servagent and Vincent Potiron and Stéphane Supiot},
url = {hal-04201747v1 },
doi = {10.1016/j.radonc.2023.109820},
issn = {1879-0887},
year  = {2023},
date = {2023-10-01},
urldate = {2023-10-01},
journal = {Radiother Oncol},
volume = {187},
pages = {109820},
abstract = {The ability to reduce toxicity of ultra-high dose rate (UHDR) helium ion irradiation has not been reported in vivo. Here, we tested UHDR helium ion irradiation in an embryonic zebrafish model. Our results show that UHDR helium ions spare body development and reduce spine curvature, compared to conventional dose rate.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{pu_drug-tolerant_2023,
title = {Drug-tolerant persister cells in cancer: the cutting edges and future directions},
author = {Yi Pu and Lu Li and Haoning Peng and Lunxu Liu and Dominique Heymann and Caroline Robert and François Vallette and Shensi Shen},
url = {https://doi.org/10.1038/s41571-023-00815-5
inserm-04501799v1 },
doi = {10.1038/s41571-023-00815-5},
issn = {1759-4782},
year  = {2023},
date = {2023-09-01},
urldate = {2023-09-01},
journal = {Nature Reviews Clinical Oncology},
abstract = {Drug-tolerant persister (DTP) cell populations were originally discovered in antibiotic-resistant bacterial biofilms. Similar populations with comparable features have since been identified among cancer cells and have been linked with treatment resistance that lacks an underlying genomic alteration. Research over the past decade has improved our understanding of the biological roles of DTP cells in cancer, although clinical knowledge of the role of these cells in treatment resistance remains limited. Nonetheless, targeting this population is anticipated to provide new treatment opportunities. In this Perspective, we aim to provide a clear definition of the DTP phenotype, discuss the underlying characteristics of these cells, their biomarkers and vulnerabilities, and encourage further research on DTP cells that might improve our understanding and enable the development of more effective anticancer therapies.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{prasanna_semisynthetic_2023,
title = {Semisynthetic Pneumococcal Glycoconjugate Nanovaccine},
author = {Maruthi Prasanna and Rubén Varela Calvino and Annie Lambert and Maria Arista Romero and Sylvia Pujals and François Trottein and Emilie Camberlein and Cyrille Grandjean and Noemi Csaba},
url = {https://doi.org/10.1021/acs.bioconjchem.3c00252
 hal-04209406v1 },
doi = {10.1021/acs.bioconjchem.3c00252},
issn = {1043-1802},
year  = {2023},
date = {2023-09-01},
urldate = {2023-09-01},
journal = {Bioconjugate Chemistry},
volume = {34},
number = {9},
pages = {1563--1575},
abstract = {Pneumococcal conjugate vaccines offer an excellent safety profile and high protection against the serotypes comprised in the vaccine. However, inclusion of protein antigens fromStreptococcus pneumoniaecombined with potent adjuvants and a suitable delivery system are expected to both extend protection to serotype strains not represented in the formulation and stimulate a broader immune response, thus more effective in young children, elderly, and immunocompromised populations. Along this line, nanoparticle (NP) delivery systems can enhance the immunogenicity of antigens by protecting them from degradation and increasing their uptake by antigen-presenting cells, as well as offering co-delivery with adjuvants. We report herein the encapsulation of a semisynthetic glycoconjugate (GC) composed of a synthetic tetrasaccharide mimicking theS. pneumoniae serotype 14 capsular polysaccharide (CP14) linked to the Pneumococcal surface protein A (PsaA) using chitosan NPs (CNPs). These GC-loaded chitosan nanoparticles (GC-CNPs) were not toxic to human monocyte-derived dendritic cells (MoDCs), showed enhanced uptake, and displayed better immunostimulatory properties in comparison to the naked GC. A comparative study was carried out in mice to evaluate the immune response elicited by the glycoconjugate-administered subcutaneously (SC), where the GC-CNPs displayed 100-fold higher IgG response as compared with the group treated with nonencapsulated GC. Overall, the study demonstrates the potential of this chitosan-based nanovaccine for efficient delivery of glycoconjugate antigens.},
note = {Publisher: American Chemical Society},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@inbook{nokey,
title = {Les plantes parasites},
author = {Philippe Delavault, Philippe Simier, Christophe Veronesi},
isbn = { 9782807302884 },
year  = {2023},
date = {2023-08-25},
urldate = {2023-08-25},
booktitle = {Phytopathologie},
volume = {Partie 2},
pages = {130-143},
publisher = {De Boeck Supérieur éditions},
edition = {Deuxième édition},
chapter = {7},
keywords = {team 4},
pubstate = {published},
tppubtype = {inbook}
}
@article{Lin2023,
title = {The dynamic duo: how DNA methylation and gene transcription help diatoms thrive in modern oceans},
author = {Xin Lin and Leïla Tirichine and Xu Zhang},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400112/
 hal-04284583v1 },
doi = {10.1093/jxb/erad205},
issn = {00220957},
year  = {2023},
date = {2023-08-03},
urldate = {2023-08-03},
journal = {Journal of Experimental Botany},
volume = {74},
issue = {14},
pages = {3879–3882},
abstract = {DNA methylation is essential for maintaining genome stability, mediating gene expression, and aiding species in adapting to their environment. Wan et al. (2023) measured the changes in phenotypic traits of the model diatom Phaeodactylum tricornutum in response to a 2-year exposure to ocean acidification, warming, or both, and analysed the concomitant changes in DNA methylation and transcriptomic patterns. Their study revealed that DNA methylation and gene transcription work in concert to enable unicellular phytoplankton to adapt to dynamic environmental changes.},
keywords = {epigenetics, team 5},
pubstate = {published},
tppubtype = {article}
}
@article{Hisanaga2023,
title = {The Polycomb repressive complex 2 deposits H3K27me3 and represses transposable elements in a broad range of eukaryotes},
author = {Tetsuya Hisanaga and Facundo Romani and Shuangyang Wu and Teresa Kowar and Yue Wu and Ruth Lintermann and Arie Fridrich and Chung Hyun Cho and Timothée Chaumier and Bhagyshree Jamge and Sean A Montgomery and Elin Axelsson and Svetlana Akimcheva and Tom Dierschke and John L Bowman and Takayuki Fujiwara and Shunsuke Hirooka and Shin-Ya Miyagishima and Liam Dolan and Leila Tirichine and Daniel Schubert and Frédéric Berger},
url = {https://www.sciencedirect.com/science/article/pii/S0960982223011533?via%3Dihub
hal-04284522v1},
doi = {10.1016/j.cub.2023.08.073},
year  = {2023},
date = {2023-08-02},
urldate = {2023-08-02},
journal = {Current Biology},
volume = {33},
issue = {20},
pages = {4367-4380.e9},
abstract = {The mobility of transposable elements (TEs) contributes to evolution of genomes. Their uncontrolled activity causes genomic instability; therefore, expression of TEs is silenced by host genomes. TEs are marked with DNA and H3K9 methylation, which are associated with silencing in flowering plants, animals, and fungi. However, in distantly related groups of eukaryotes, TEs are marked by H3K27me3 deposited by the Polycomb repressive complex 2 (PRC2), an epigenetic mark associated with gene silencing in flowering plants and animals. The direct silencing of TEs by PRC2 has so far only been shown in one species of ciliates. To test if PRC2 silences TEs in a broader range of eukaryotes, we generated mutants with reduced PRC2 activity and analyzed the role of PRC2 in extant species along the lineage of Archaeplastida and in the diatom P. tricornutum. In this diatom and the red alga C. merolae, a greater proportion of TEs than genes were repressed by PRC2, whereas a greater proportion of genes than TEs were repressed by PRC2 in bryophytes. In flowering plants, TEs contained potential cis-elements recognized by transcription factors and associated with neighbor genes as transcriptional units repressed by PRC2. Thus, silencing of TEs by PRC2 is observed not only in Archaeplastida but also in diatoms and ciliates, suggesting that PRC2 deposited H3K27me3 to silence TEs in the last common ancestor of eukaryotes. We hypothesize that during the evolution of Archaeplastida, TE fragments marked with H3K27me3 were selected to shape transcriptional regulation, controlling networks of genes regulated by PRC2.},
keywords = {epigenetics, team 5},
pubstate = {published},
tppubtype = {article}
}
@article{Wu2023b,
title = {Chromosome-Wide Distribution and Characterization of H3K36me3 and H3K27Ac in the Marine Model Diatom Phaeodactylum tricornutum},
author = {Yue Wu and Leila Tirichine },
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421102/
hal-04284555v1 },
doi = { 10.3390/plants12152852},
year  = {2023},
date = {2023-08-02},
urldate = {2023-08-02},
journal = {Plants (Basel)},
volume = {12},
issue = {15},
pages = {2852},
keywords = {epigenetics, team 5},
pubstate = {published},
tppubtype = {article}
}
@article{pmid37640279,
title = {Vitislactone, a non-canonical strigolactone exudated by grapevine rootstocks in response to nitrogen starvation},
author = {Vincent Lailheugue and Isabelle Merlin and Stéphanie Boutet and François Perreau and Jean-Bernard Pouvreau and Sabine Delgrange and Paul-Henri Ducrot and Betty Cottyn-Boitte and Gregory Mouille and Virginie Lauvergeat},
url = { hal-04247159v1 },
doi = {10.1016/j.phytochem.2023.113837},
issn = {1873-3700},
year  = {2023},
date = {2023-08-01},
urldate = {2023-08-01},
journal = {Phytochemistry},
volume = {215},
pages = {113837},
abstract = {Strigolactones are compounds produced by plant roots in response to nutrient deficiency, acting both as local and systemic signals to control development and nutrition. Strigolactones are exuded in the rhizosphere to positively influence interactions with beneficial microbes. LC-MS/MS analysis shows that two genetically distinct grapevine rootstocks exudate one or two non-canonical strigolactones when subjected to low nitrogen conditions. Gene expression profiles and orobanche seed germination assays confirm that the biosynthesis and exudation of non-canonical compounds is the preferred pathway. The first compound, corresponding to heliolactone or 6-epi-heliolactone, is only exuded by the rootstock showing lower shoot branching and a higher level of mycorrhization with arbuscular mycorrhizal fungi. The structure of the second compound exuded by both rootstocks was identified by NMR and LC-MS/MS analysis. It is a non-canonical strigolactone, which has never been identified in another species. This first identification of a natural compound with the potential to stimulate beneficial root-microbe interactions in grapevines opens new perspectives in viticulture.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{depienne_click-electrochemistry_2023,
title = {Click-electrochemistry for the rapid labeling of virus, bacteria and cell surfaces},
author = {Sébastien Depienne and Mohammed Bouzelha and Emmanuelle Courtois and Karine Pavageau and Pierre-Alban Lalys and Maia Marchand and Dimitri Alvarez-Dorta and Steven Nedellec and Laura Marín-Fernández and Cyrille Grandjean and Mohammed Boujtita and David Deniaud and Mathieu Mével and Sébastien G. Gouin},
url = {https://doi.org/10.1038/s41467-023-40534-0
https://dx.doi.org/10.26434/chemrxiv-2023-q3sd8
hal-04246348v1 },
doi = {10.1038/s41467-023-40534-0},
issn = {2041-1723},
year  = {2023},
date = {2023-08-01},
urldate = {2023-08-01},
journal = {Nature Communications},
volume = {14},
number = {1},
pages = {5122},
abstract = {Methods for direct covalent ligation of microorganism surfaces remain poorly reported, and mostly based on metabolic engineering for bacteria and cells functionalization. While effective, a faster method avoiding the bio-incorporation step would be highly complementary. Here, we used N-methylluminol (NML), a fully tyrosine-selective protein anchoring group after one-electron oxidation, to label the surface of viruses, living bacteria and cells. The functionalization was performed electrochemically and in situ by applying an electric potential to aqueous buffered solutions of tagged NML containing the viruses, bacteria or cells. The broad applicability of the click-electrochemistry method was explored on recombinant adeno-associated viruses (rAAV2), Escherichia coli (Gram-) and Staphyloccocus epidermidis (Gram + ) bacterial strains, and HEK293 and HeLa eukaryotic cell lines. Surface electro-conjugation was achieved in minutes to yield functionalized rAAV2 that conserved both structural integrity and infectivity properties, and living bacteria and cell lines that were still alive and able to divide.},
keywords = {MIMOVAX, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{pmid37601883,
title = {MYH9-related disease: Assessment of the pathogenicity of a new mutation},
author = {Babuty Antoine and Pierre Boisseau and Nicolas Drillaud and Marion Eveillard and Marc Fouassier},
doi = {10.1002/jha2.715},
issn = {2688-6146},
year  = {2023},
date = {2023-08-01},
urldate = {2023-08-01},
journal = {EJHaem},
volume = {4},
number = {3},
pages = {869--871},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{nokey,
title = {A student-based expansion of the strategies of reproduction in fish (STOREFISH) database to 288 North American freshwater and anadromous species for 14 egg and larval traits},
author = {Paul Venturell and Stéphane Teletchea and Bales A.M., Bartolozzi P., Bird A.T., Blevins T.K., Campaniello S.J., Caizergue M., Carlu L., Chancerelle G., Colletta B., Dauphin L., Doche B., Derolf P.M., De Wever T., Dewig E.M., Dixon L.M., Durand C., Eck M., Faatauira T., Fisher S.M., Fix G., Fournier S., Gauthy A., Golitin C., Guyader S., Hachet F., Harnay P., Hawkins S.G., Kaufling A., Khan M., Kesterson W.J., Klein M.K., Lejeune C., Loiseau J., Loyau R., Luginbuhl S.B., Maeso J., Marc T., Martineau L., Meurillon T., Mesnieres E., Mohra R., Mccord A.O., Mcdonald Z.N., Mckay A.B., Miller T., Minhinnett S.R., Poujoulat R., Profit V., Psurny G.Q., Raymond G., Redinger R.R., Rech G., Rider A.L., Rodriguez L., Sanders S.S., Salou G., Saucier T.E., Schwer J.D., Seymour R.D., Seznec C., Shook B.L., Soler J., Tettling L., Thornburg G.E., Tottoli T., Veber E., Verdier L., Verin R., Vigot M., Vigouroux E., Voss K.N., Weir J.L. and Fabrice Teletchea},
editor = {Société Française d&#039;Ichtyologie},
url = {https://sfi-cybium.fr/fr/student-based-expansion-strategies-reproduction-fish-storefish-database-288-north-american},
doi = {10.26028/cybium/2023-006},
isbn = {0399-0974},
year  = {2023},
date = {2023-07-01},
urldate = {2023-07-01},
journal = {Cybium},
volume = {47},
issue = {3},
pages = {315-323},
abstract = {Teleosts exhibit the highest reproductive diversity of all vertebrates, but this diversity has not been extensively analyzed, in part due to a lack of synthesis of life history information. The original STOREFISH (STrategies Of REproduction in FISH) database was published in 2007, and then released online in 2020 to facilitate data visualization and utilization (www.storefish.org). The original database contains information on 50 life history traits from ~1,200 references for 80 freshwater and anadromous species, mostly from Europe. Here, we describe the process and results of an international effort to update and extend the database for 14 egg and larval traits from North American freshwater and anadromous species, and then reassess previous bivari- ate relationships. Students in the United States and France used data from nearly 800 references to increase the STOREFISH database to 8,081 records (70% increase) for 368 species (360% increase) and 41 families (116% increase). We extracted fewer records per species than the original database because we included many species for which relatively little information was known. However, the distribution of records among trait values was similar to the original database. Updating and expanding the database improved the accuracy of the incuba- tion time-temperature relationship below 10°C, and challenged a previous assumption regarding the larval size- egg diameter relationship. Our expansion effort progressed smoothly and quickly via an educational model that emphasized supervised research and collaboration. We are extending this approach to include validators for data curation, and both pure and applied research that demonstrates the utility of the STOREFISH database to biodi- versity research, conservation, assessment, management, and aquaculture.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{pmid37148979,
title = {Pharmacological options in the treatment of osteogenesis imperfecta: A comprehensive review of clinical and potential alternatives},
author = {Javier Muñoz-Garcia and Dominique Heymann and Irina Giurgea and Marie Legendre and Serge Amselem and Beatriz Castañeda and Frédéric Lézot and Jorge William Vargas-Franco},
url = { inserm-04100355v1 },
doi = {10.1016/j.bcp.2023.115584},
issn = {1873-2968},
year  = {2023},
date = {2023-07-01},
urldate = {2023-07-01},
journal = {Biochem Pharmacol},
volume = {213},
pages = {115584},
abstract = {Osteogenesis imperfecta (OI) is a genetically heterogeneous connective tissue disorder characterized by bone fragility and different extra-skeletal manifestations. The severity of these manifestations makes it possible to classify OI into different subtypes based on the main clinical features. This review aims to outline and describe the current pharmacological alternatives for treating OI, grounded on clinical and preclinical reports, such as antiresorptive agents, anabolic agents, growth hormone, and anti-TGFβ antibody, among other less used agents. The different options and their pharmacokinetic and pharmacodynamic properties will be reviewed and discussed, focusing on the variability of their response and the molecular mechanisms involved to attain the main clinical goals, which include decreasing fracture incidence, improving pain, and promoting growth, mobility, and functional independence.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{panez-toro_advances_2023,
title = {Advances in Osteosarcoma},
author = {Isidora Panez-Toro and Javier Muñoz-García and Jorge W. Vargas-Franco and Axelle Renodon-Cornière and Marie-Françoise Heymann and Frédéric Lézot and Dominique Heymann},
url = {https://link.springer.com/10.1007/s11914-023-00803-9
inserm-04119793v1 },
doi = {10.1007/s11914-023-00803-9},
issn = {1544-1873, 1544-2241},
year  = {2023},
date = {2023-06-01},
urldate = {2023-06-01},
journal = {Current Osteoporosis Reports},
abstract = {Purpose of Review
This article gives a brief overview of the most recent developments in osteosarcoma treatment, including targeting of signaling pathways, immune checkpoint inhibitors, drug delivery strategies as single or combined approaches, and the identification of new therapeutic targets to face this highly heterogeneous disease.

Recent Findings
Osteosarcoma is one of the most common primary malignant bone tumors in children and young adults, with a high risk of bone and lung metastases and a 5-year survival rate around 70% in the absence of metastases and 30% if metastases are detected at the time of diagnosis. Despite the novel advances in neoadjuvant chemotherapy, the effective treatment for osteosarcoma has not improved in the last 4 decades. The emergence of immunotherapy has transformed the paradigm of treatment, focusing therapeutic strategies on the potential of immune checkpoint inhibitors. However, the most recent clinical trials show a slight improvement over the conventional polychemotherapy scheme.

Summary
The tumor microenvironment plays a crucial role in the pathogenesis of osteosarcoma by controlling the tumor growth, the metastatic process and the drug resistance and paved the way of new therapeutic options that must be validated by accurate pre-clinical studies and clinical trials.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{loussouarn_spatial_2023,
title = {Spatial Distribution of Immune Cells in Primary and Recurrent Glioblastoma: A Small Case Study},
author = {Delphine Loussouarn and Lisa Oliver and Celine Salaud and Edouard Samarut and Raphaël Bourgade and Christophe Béroud and Emilie Morenton and Dominique Heymann and Francois M. Vallette},
url = {https://www.mdpi.com/2072-6694/15/12/3256
hal-04254114v1 },
doi = {10.3390/cancers15123256},
issn = {2072-6694},
year  = {2023},
date = {2023-06-01},
urldate = {2023-06-01},
journal = {Cancers},
volume = {15},
number = {12},
pages = {3256},
abstract = {Only a minority of patients with glioblastoma (GBM) respond to immunotherapy, and always only partially. There is a lack of knowledge on immune distribution in GBM and in its tumor microenvironment (TME). To address the question, we used paired primary and recurrent tumors from GBM patients to study the composition and the evolution of the immune landscape upon treatment. We studied the expression of a handful of immune markers (CD3, CD8, CD68, PD-L1 and PD-1) in GBM tissues in 15 paired primary and recurrent GBM. In ﬁve selected patients, we used Nanostring Digital Spatial Proﬁling (DSP) to obtain simultaneous assessments of multiple biomarkers both within the tumor and the microenvironment in paired primary and recurrent GBM. Our results suggest that the evolution of the immune landscape between paired primary and recurrent GBM tumors is highly heterogeneous. However, our study identiﬁes B3-H7 and HLA-DR as potential targets in primary and recurrent GBM. Spatial proﬁling of immune markers from matched primary and recurrent GBM shows a nonlinear complex evolution during the progression of cancer. Nonetheless, our study demonstrated a global increase in macrophages, and revealed differential localization of some markers, such as B7-H3 and HLA-DR, between GBM and its TME.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{pmid37382440,
title = {Modulation of the functional interfaces between retroviral intasomes and the human nucleosome},
author = {E Mauro and D Lapaillerie and C Tumiotto and Cathy Charlier and F Martins and S F Sousa and M Métifiot and Pierre Weigel and K Yamatsugu and M Kanai and H Munier-Lehmann and C Richetta and M Maisch and J Dutrieux and J Batisse and M Ruff and O Delelis and P Lesbats and V Parissi},
doi = {10.1128/mbio.01083-23},
issn = {2150-7511},
year  = {2023},
date = {2023-06-01},
urldate = {2023-06-01},
journal = {mBio},
pages = {e0108323},
abstract = {Infection by retroviruses as HIV-1 requires the stable integration of their genome into the host cells. This process needs the formation of integrase (IN)-viral DNA complexes, called intasomes, and their interaction with the target DNA wrapped around nucleosomes within cell chromatin. To provide new tools to analyze this association and select drugs, we applied the AlphaLISA technology to the complex formed between the prototype foamy virus (PFV) intasome and nucleosome reconstituted on 601 Widom sequence. This system allowed us to monitor the association between both partners and select small molecules that could modulate the intasome/nucleosome association. Using this approach, drugs acting either on the DNA topology within the nucleosome or on the IN/histone tail interactions have been selected. Within these compounds, doxorubicin and histone binders calixarenes were characterized using biochemical,  molecular simulations and cellular approaches. These drugs were shown to inhibit both PFV and HIV-1 integration . Treatment of HIV-1-infected PBMCs with the selected molecules induces a decrease in viral infectivity and blocks the integration process. Thus, in addition to providing new information about intasome-nucleosome interaction determinants, our work also paves the way for further unedited antiviral strategies that target the final step of intasome/chromatin anchoring. IMPORTANCE In this work, we report the first monitoring of retroviral intasome/nucleosome interaction by AlphaLISA. This is the first description of the AlphaLISA application for large nucleoprotein complexes (&gt;200 kDa) proving that this technology is suitable for molecular characterization and bimolecular inhibitor screening assays using such large complexes. Using this system, we have identified new drugs disrupting or preventing the intasome/nucleosome complex and inhibiting HIV-1 integration both  and in infected cells. This first monitoring of the retroviral/intasome complex should allow the development of multiple applications including the analyses of the influence of cellular partners, the study of additional retroviral intasomes, and the determination of specific interfaces. Our work also provides the technical bases for the screening of larger libraries of drugs targeting specifically these functional nucleoprotein complexes, or additional nucleosome-partner complexes, as well as for their characterization.},
keywords = {impact},
pubstate = {published},
tppubtype = {article}
}
@conference{nokey,
title = {Environnement dosimétrique et premiers résultats des études sur les mécanismes physico-chimiques et biologiques de l&#039;hadronthérapie FLASH au cyclotron ARRONAX},
author = { Manon Evin , Charbel Koumeir , Quentin Mouchard , Guillaume Blain , Craff Emeline , Grégory Delpon , Vincent Fiegel , Giovanna Rosa Fois, Youssef Ghannam , Ferid Haddad , Lydia Maigne, Vincent Potiron , Gaëlle Saade, Noël Servagent , Stéphane Supiot , Johan Vandenborre , Sarra Terfas , Vincent Métivier , Sophie Chiavassa},
url = { hal-04246385v1 },
year  = {2023},
date = {2023-06-01},
urldate = {2023-06-01},
keywords = {team 3},
pubstate = {published},
tppubtype = {conference}
}
@article{sanejouand2023unknown,
title = {On the unknown proteins of eukaryotic proteomes},
author = {Yves-Henri Sanejouand},
url = {https://doi.org/10.1007/s00239-023-10116-1
hal-03863835},
doi = {10.1007/s00239-023-10116-1},
year  = {2023},
date = {2023-05-23},
urldate = {2023-05-23},
journal = {Journal of Molecular Evolution},
volume = {91},
pages = {492-501},
abstract = {In order to study unknown proteins on a large scale, a reference system has been set up for the three major eukaryotic lineages, built with 36 proteomes as taxonomically diverse as possible. Proteins from 362 eukaryotic proteomes with no known homologue in this set were then analyzed, focusing noteworthy on singletons, that is, on unknown proteins with no known homologue in their own proteome. Consistently, according to Uniprot, for a given species, no more than 12% of the singletons thus found are known at the protein level. Also, since they rely on the information found in the alignment of homologous sequences, predictions of AlphaFold2 for their tridimensional structure are usually poor. In the case of metazoan species, the number of singletons seems to increase as a function of the evolutionary distance from the reference system. Interestingly, no such trend is found in the cases of viridiplantae and fungi, as if the timescale on which singletons are added to proteomes were different in metazoa and in other eukaryotic kingdoms. In order to confirm this phenomenon, further studies of proteomes closer to those of the reference system are however needed.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{Wu2023,
title = {PhaeoEpiView: an epigenome browser of the newly assembled genome of the model diatom Phaeodactylum tricornutum},
author = {Yue Wu and Timothée Chaumier and Eric Manirakiza and Alaguraj Veluchamy and Leila Tirichine},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206091/
hal-04284562v1 },
doi = { 10.1038/s41598-023-35403-1},
issn = {2045-2322},
year  = {2023},
date = {2023-05-23},
urldate = {2023-05-23},
journal = {Scientific Reports },
volume = {13},
pages = {8320},
abstract = {Recent advances in DNA sequencing technologies particularly long-read sequencing, greatly improved genomes assembly. However, this has created discrepancies between published annotations and epigenome tracks, which have not been updated to keep pace with the new assemblies. Here, we used the latest improved telomere-to-telomere assembly of the model pennate diatom Phaeodactylum tricornutum to lift over the gene models from Phatr3, a previously annotated reference genome. We used the lifted genes annotation and newly published transposable elements to map the epigenome landscape, namely DNA methylation and post-translational modifications of histones. This provides the community with PhaeoEpiView, a browser that allows the visualization of epigenome data and transcripts on an updated and contiguous reference genome, to better understand the biological significance of the mapped data. We updated previously published histone marks with a more accurate peak calling using mono instead of poly(clonal) antibodies and deeper sequencing. PhaeoEpiView (https://PhaeoEpiView.univ-nantes.fr) will be continuously updated with the newly published epigenomic data, making it the largest and richest epigenome browser of any stramenopile. In the upcoming era of molecular environmental studies, where epigenetics plays a significant role, we anticipate that PhaeoEpiView will become a widely used tool.},
keywords = {epigenetics, team 5},
pubstate = {published},
tppubtype = {article}
}
@article{demonceaux2023enzymatic,
title = {Enzymatic synthesis, characterization and molecular docking of a new functionalized polyphenol: Resveratrol-3, 4’-⍺-diglucoside},
author = {Marie Demonceaux and Marine Goux and Lucia Emanueli Schimith and Michele Goulart Dos Santos and Johann Hendrickx and Bernard Offmann and Corinne André-Miral},
url = {https://www.sciencedirect.com/science/article/pii/S2211715623001959},
doi = {10.1016/j.rechem.2023.100956},
year  = {2023},
date = {2023-05-16},
urldate = {2023-05-16},
journal = {Results in Chemistry},
pages = {100956},
publisher = {Elsevier},
abstract = {Transglucosylation of resveratrol by the Q345F variant of sucrose phosphorylase from Bifidobacterium adolescentis (BaSP) was extensively studied during the last decade. Indeed, Q345F is able to catalyze the synthesis of resveratrol-3-O-⍺-D-glucoside (RES-3) with yield up to 97% using a cost-effective glucosyl donor, sucrose (Kraus et al., Chemical Communications, 53(90), 12182–12184 (2017)). Despite the fact that two further products were detectable in low amounts after glucoside synthesis, they were never identified. Here, we isolated and fully characterized one of those two minor products: resveratrol-3,4′-O-⍺-D-diglucoside (RES-3,4′). This original compound had never been described before. Using bioinformatics models, we successfully explained the formation of this diglucosylated product. Indeed, with RES-3 as acceptor substrate, Q345F is able to transfer a glucosyl moiety in position 4′-OH, what had been reported as impossible in the literature. The low yield observed is due to the steric hindrance into the catalytic site between RES-3 and residues Tyr132 and Tyr344. Nevertheless, the substrate orientation in the active site is favored by stabilizing interactions. Ring A of RES-3 bearing the diol moiety is stabilized by hydrogen bonds with residues Asp50, Arg135, Asn347 and Arg399. Hydroxyl group OH-4′ shares hydrogen bonds with the catalytic residues Asp192 and Glu232. Multiple hydrophobic contacts complete the stabilization of the substrate to favor the glucosylation at position 4′. Understanding of the mechanisms allowing the glucosylation at position 4′ of resveratrol will help the development of enzymatic tools to target and control the enzymatic synthesis of original ⍺-glucosylated polyphenols with high added value and better biodisponibility.},
keywords = {Funregiox, team 1, team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{biomedinformatics3020021,
title = {Evaluation of Transmembrane Protein Structural Models Using HPMScore},
author = {Stéphane Téletchéa and Jérémy Esque and Aurélie Urbain and Catherine Etchebest and Alexandre G. de Brevern},
url = {https://www.mdpi.com/2673-7426/3/2/21
https://hal.science/hal-03251546v1, HAL},
doi = {10.3390/biomedinformatics3020021},
issn = {2673-7426},
year  = {2023},
date = {2023-05-02},
urldate = {2023-05-02},
journal = {BioMedInformatics},
volume = {3},
number = {2},
pages = {306--326},
abstract = {Transmembrane proteins (TMPs) are a class of essential proteins for biological and therapeutic purposes. Despite an increasing number of structures, the gap with the number of available sequences remains impressive. The choice of a dedicated function to select the most probable/relevant model among hundreds is a specific problem of TMPs. Indeed, the majority of approaches are mostly focused on globular proteins. We developed an alternative methodology to evaluate the quality of TMP structural models. HPMScore took into account sequence and local structural information using the unsupervised learning approach called hybrid protein model. The methodology was extensively evaluated on very different TMP all-&alpha; proteins. Structural models with different qualities were generated, from good to bad quality. HPMScore performed better than DOPE in recognizing good comparative models over more degenerated models, with a Top 1 of 46.9% against DOPE 40.1%, both giving the same result in 13.0%. When the alignments used are higher than 35%, HPM is the best for 52%, against 36% for DOPE (12% for both). These encouraging results need further improvement particularly when the sequence identity falls below 35%. An area of enhancement would be to train on a larger training set. A dedicated web server has been implemented and provided to the scientific community. It can be used with structural models generated from comparative modeling to deep learning approaches.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{cancers15061898,
title = {Comparison of Hormone-Sensitive Oligorecurrent Prostate Cancer Patients Based on Routine Use of Choline and/or PSMA PET/CT to Guide Metastasis-Directed Therapy},
author = {Raphaël Metz and Aurore Rauscher and Loïg Vaugier and Stéphane Supiot and Franck Drouet and Loic Campion and Caroline Rousseau},
url = {https://www.mdpi.com/2072-6694/15/6/1898},
doi = {10.3390/cancers15061898},
issn = {2072-6694},
year  = {2023},
date = {2023-03-22},
urldate = {2023-01-01},
journal = {Cancers},
volume = {15},
number = {6},
abstract = {Background: In hormone-sensitive oligorecurrent prostate cancer (PC), the literature showed [68Ga]Ga-PSMA (PSMA) and [18F]F-choline (FCH) PET/CT can successfully guide metastasis-directed therapies (MDT). This observational retrospective study aimed to explore, in routine use, the impact of FCH or PSMA PET/CT in guiding MDT for hormone-sensitive oligometastatic PC at different recurrences. Methods: In 2017-2020, patients initially treated with radical prostatectomy but, in biochemical recurrence (with PSA &le; 2 ng/mL), diagnosed as oligometastatic based on FCH or PSMA PET/CT, were identified. MDT was stereotactic body radiotherapy (SBRT), elective nodal or prostate bed radiotherapy &plusmn; boost and &plusmn; androgen deprivation therapy (ADT). The primary endpoint was biochemical relapse-free survival (BR-FS), defined as a PSA increase &ge; 0.2 ng/mL above the nadir and increasing over two successive samples and the secondaries were ADT-free survival (ADT-FS). Results: 123 patients (70 PSMA and 53 FCH) were included. The median follow-up was 42.2 months. The median BR-FS was 24.7 months in the PSMA group versus 13.0 months in the FCH group (p = 0.008). Similarly, ADT-FS (p = 0.001) was longer in patients in the PSMA group. In multivariate analysis, a short PSA doubling time before imaging (p = 0.005) and MDT with SBRT (p = 0.001) were poor prognostic factors for BR-FS. Conclusions: Routine use of FCH or PSMA PET/CT in hormone-sensitive PC showed an advantage for using PSMA PET/CT to guide MDT in terms of BR-FS and ADT-FS in patients with low PSA value. Prospective studies are needed to confirm these hypotheses.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{violo2023site,
title = {Site-Selective Unnatural Amino Acid Incorporation at Single or Multiple Positions to Control Sugar-Protein Connectivity in Glycoconjugate Vaccine Candidates},
author = {Typhaine Violo and Annie Lambert and Aline Pillot and Mathieu Fanuel and Jessica Mac-Béar and Cédric Broussard and Cyrille Grandjean and Emilie Camberlein},
url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/chem.202203497
hal-03918892v2 
},
doi = {10.1002/chem.202203497},
isbn = {1521-3765},
year  = {2023},
date = {2023-03-13},
urldate = {2023-03-13},
journal = {Chemistry--A European Journal},
volume = {29},
number = {15},
pages = {e202203497},
publisher = {Wiley Online Library},
abstract = {In cellulo site-specific unnatural amino acid incorporation based on amber stop codon reassignment is a powerful tool to modify proteins at defined positions. This technique is herein applied to the selective functionalization of the Pneumococcal surface adhesin A protein at three distinct positions. Nϵ-propargyloxycarbonyl-l-lysine residues were incorporated and their alkyne groups reacted using click-chemistry with a synthetic azido-functionalized tetrasaccharide representative of one repeat unit of the Streptococcus pneumoniae serotype 14 capsular polysaccharide. Anti-PsaA antibody response induced in mice by the trivalent glycoconjugate was determined in comparison with corresponding monovalent and randomly functionalized conjugates. Our results suggest that controlled was superior to random conjugation for preserving antigenicity. In definitive, the reported strategy offers a unique opportunity to study the impact of carbohydrate antigen-carrier protein connectivity on immunogenicity.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{Hoguin2023,
title = {The model diatom Phaeodactylum tricornutum provides insights into the diversity and function of microeukaryotic DNA methyltransferases},
author = {Antoine Hoguin and Feng Yang and Agnès Groisillier and Chris Bowler and Auguste Genovesio and Ouardia Ait-Mohamed and Fabio Rocha Jimenez Vieira and Leila Tirichine},
editor = {Nature},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998398/
hal-04024906v1 },
doi = {10.1038/s42003-023-04629-0 },
issn = {23993642},
year  = {2023},
date = {2023-03-09},
urldate = {2023-03-09},
journal = {Communications Biology},
volume = {6},
number = {1},
issue = {1},
pages = {253},
abstract = {Cytosine methylation is an important epigenetic mark involved in the transcriptional control of transposable elements in mammals, plants and fungi. The Stramenopiles-Alveolate-Rhizaria (SAR) lineages are a major group of ecologically important marine microeukaryotes, including the phytoplankton groups diatoms and dinoflagellates. However, little is known about their DNA methyltransferase diversity. Here, we performed an in-silico analysis of DNA methyltransferases found in marine microeukaryotes and showed that they encode divergent DNMT3, DNMT4, DNMT5 and DNMT6 enzymes. Furthermore, we found three classes of enzymes within the DNMT5 family. Using a CRISPR/Cas9 strategy we demonstrated that the loss of the DNMT5a gene correlates with a global depletion of DNA methylation and overexpression of young transposable elements in the model diatom Phaeodactylum tricornutum. The study provides a view of the structure and function of a DNMT family in the SAR supergroup using an attractive model species.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{pmid36990245,
title = {Synthesis and Biological Evaluation of DIDS Analogues as Efficient Inhibitors of RAD51 Involved in Homologous Recombination},
author = {Alexandre Demeyer and Lucie Fonteneau and Marion Liennard and Claire Foyer and Pierre Weigel and Adèle Laurent and Jacques Lebreton and Fabrice Fleury and Monique Mathé-Allainmat},
url = {hal-04234850v1 },
doi = {10.1016/j.bmcl.2023.129261},
issn = {1464-3405},
year  = {2023},
date = {2023-03-01},
urldate = {2023-03-01},
journal = {Bioorg Med Chem Lett},
pages = {129261},
abstract = {RAD51 is a pivotal protein of the homologous recombination DNA repair pathway, and is overexpressed in some cancer cells, disrupting then the efficiency of cancer-treatments. The development of RAD51 inhibitors appears as a promising solution to restore these cancer cells sensitization to radio- or chemotherapy. From a small molecule identified as a modulator of RAD51, the 4,4&#039;-diisothiocyanostilbene-2,2&#039;-disulfonic acid (DIDS), two series of analogues with small or bulky substituents on the aromatic parts of the stilbene moiety were prepared for a structure-activity relationship study. Three compounds, the cyano analogue (12), and benzamide (23) or phenylcarbamate (29) analogues of DIDS were characterized as novel potent RAD51 inhibitors with HR inhibition in the micromolar range.},
keywords = {piramid, team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{saade2023ultrahigh,
title = {Ultrahigh-Dose-Rate Proton Irradiation Elicits Reduced Toxicity in Zebrafish Embryos},
author = {Gaëlle Saade and Eva Bogaerts and Sophie Chiavassa and Guillaume Blain and Grégory Delpon and Manon Evin and Youssef Ghannam and Ferid Haddad and Karin Haustermans and Charbel Koumeir and others},
url = {https://www.sciencedirect.com/science/article/pii/S2452109422002305
hal-03940364v1 },
doi = {10.1016/j.adro.2022.101124},
year  = {2023},
date = {2023-03-01},
urldate = {2023-03-01},
journal = {Advances in Radiation Oncology},
volume = {8},
number = {2},
pages = {101124},
publisher = {Elsevier},
abstract = {Purpose
Recently, ultrahigh-dose-rate radiation therapy (UHDR-RT) has emerged as a promising strategy to increase the benefit/risk ratio of external RT. Extensive work is on the way to characterize the physical and biological parameters that control the so-called “Flash” effect. However, this healthy/tumor differential effect is observable in in vivo models, which thereby drastically limits the amount of work that is achievable in a timely manner.

Methods and Materials
In this study, zebrafish embryos were used to compare the effect of UHDR irradiation (8-9 kGy/s) to conventional RT dose rate (0.2 Gy/s) with a 68 MeV proton beam. Viability, body length, spine curvature, and pericardial edema were measured 4 days postirradiation.

Results
We show that body length is significantly greater after UHDR-RT compared with conventional RT by 180 µm at 30 Gy and 90 µm at 40 Gy, while pericardial edema is only reduced at 30 Gy. No differences were obtained in terms of survival or spine curvature.

Conclusions
Zebrafish embryo length appears as a robust endpoint, and we anticipate that this model will substantially fasten the study of UHDR proton-beam parameters necessary for “Flash.”},
keywords = {team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{demonceaux2023regioselective,
title = {Regioselective glucosylation of (+)-catechin using a new variant of sucrose phosphorylase from Bifidobacterium adolescentis},
author = {Marie Demonceaux and Marine Goux and Johann Hendrickx and Claude Solleux and Frédéric Cadet and Émilie Lormeau and Bernard Offmann and Corinne André-Miral},
doi = {10.1039/D3OB00191A},
year  = {2023},
date = {2023-02-22},
urldate = {2023-02-22},
journal = {Organic & Biomolecular Chemistry},
volume = {21},
number = {11},
pages = {2307--2311},
publisher = {Royal Society of Chemistry},
abstract = {Mutation Q345F in sucrose phosphorylase from Bifidobacterium adolescentis (BaSP) has shown to allow efficient (+)-catechin glucosylation yielding a regioisomeric mixture: (+)-catechin-3′-O-α-D-glucopyranoside, (+)-catechin-5-O-α-D-glucopyranoside and (+)-catechin-3′,5-O-α-D-diglucopyranoside with a ratio of 51 : 25 : 24. Here, we efficiently increased the control of (+)-catechin glucosylation regioselectivity with a new variant Q345F/P134D. The same products were obtained with a ratio of 82 : 9 : 9. Thanks to bioinformatics models, we successfully explained the glucosylation favoured at the OH-3′ position due to the mutation P134D.},
keywords = {Funregiox, team 1, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{ijms24054347b,
title = {Label-Free Multiplexed Microfluidic Analysis of Protein Interactions Based on Photonic Crystal Surface Mode Imaging},
author = {Galina Nifontova and Irina Petrova and Evgeniia Gerasimovich and Valery N. Konopsky and Nizar Ayadi and Cathy Charlier and Fabrice Fleury and Alexander Karaulov and Alyona Sukhanova and Igor Nabiev},
url = {https://www.mdpi.com/1422-0067/24/5/4347},
doi = {10.3390/ijms24054347},
issn = {1422-0067},
year  = {2023},
date = {2023-02-22},
urldate = {2023-02-22},
journal = {International Journal of Molecular Sciences},
volume = {24},
number = {5},
abstract = {High-throughput protein assays are crucial for modern diagnostics, drug discovery, proteomics, and other fields of biology and medicine. It allows simultaneous detection of hundreds of analytes and miniaturization of both fabrication and analytical procedures. Photonic crystal surface mode (PC SM) imaging is an effective alternative to surface plasmon resonance (SPR) imaging used in conventional gold-coated, label-free biosensors. PC SM imaging is advantageous as a quick, label-free, and reproducible technique for multiplexed analysis of biomolecular interactions. PC SM sensors are characterized by a longer signal propagation at the cost of a lower spatial resolution, which makes them more sensitive than classical SPR imaging sensors. We describe an approach for designing label-free protein biosensing assays employing PC SM imaging in the microfluidic mode. Label-free, real-time detection of PC SM imaging biosensors using two-dimensional imaging of binding events has been designed to study arrays of model proteins (antibodies, immunoglobulin G-binding proteins, serum proteins, and DNA repair proteins) at 96 points prepared by automated spotting. The data prove feasibility of simultaneous PC SM imaging of multiple protein interactions. The results pave the way to further develop PC SM imaging as an advanced label-free microfluidic assay for the multiplexed detection of protein interactions.},
keywords = {freebiowave, impact, team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{nokey,
title = {Editorial: Algal symbiotic relationships in freshwater and marine environments},
author = {Leila Tirichine and Gwenael Piganeau},
url = {https://www.frontiersin.org/articles/10.3389/fpls.2023.1155759/full
hal-04284580v1 },
doi = {doi: 10.3389/fpls.2023.1155759},
year  = {2023},
date = {2023-02-20},
urldate = {2023-02-20},
journal = {Front. Plant Sci.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{nokey,
title = {Characterization of a Marine Diatom Chitin Synthase Using a Combination of Meta-Omics, Genomics, and Heterologous Expression Approaches. },
author = {Zhanru Shao and Osei Ampomah andFabio Vieira and Richard Dorrell and Shaoxuan Li and Leila Tirichine and Vincent Bulone and Delin Duan and Chris Bowler},
doi = {doi: 10.1128/msystems.01131-22},
year  = {2023},
date = {2023-02-15},
urldate = {2023-02-15},
journal = {mSystems},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{10.7554/eLife.82037,
title = {Specific targeting of inflammatory osteoclastogenesis by the probiotic yeast S. boulardii CNCM I-745 reduces bone loss in osteoporosis},
author = {Maria-Bernadette Madel and Julia Halper and Lidia Ibáñez and Lozano Claire and Matthieu Rouleau and Antoine Boutin and Adrien Mahler and Rodolphe Pontier-Bres and Thomas Ciucci and Majlinda Topi and Christophe Hue and Jerome Amiaud and Salvador Iborra and David Sancho and Dominique Heymann and Henri-Jean Garchon and Dorota Czerucka and Florence Apparailly and Isabelle Duroux-Richard and Abdelilah Wakkach and Claudine Blin-Wakkach},
editor = {Yi-Ping Li and Mone Zaidi and Marco Ponzetti},
url = {https://doi.org/10.7554/eLife.82037},
doi = {10.7554/eLife.82037},
issn = {2050-084X},
year  = {2023},
date = {2023-02-01},
urldate = {2023-02-01},
journal = {eLife},
volume = {12},
pages = {e82037},
publisher = {eLife Sciences Publications, Ltd},
abstract = {Bone destruction is a hallmark of chronic inflammation, and bone-resorbing osteoclasts arising under such a condition differ from steady-state ones. However, osteoclast diversity remains poorly explored. Here, we combined transcriptomic profiling, differentiation assays and in vivo analysis in mouse to decipher specific traits for inflammatory and steady-state osteoclasts. We identified and validated the pattern-recognition receptors (PRR) Tlr2, Dectin-1, and Mincle, all involved in yeast recognition as major regulators of inflammatory osteoclasts. We showed that administration of the yeast probiotic textitSaccharomyces boulardii CNCM I-745 (textitSb) in vivo reduced bone loss in ovariectomized but not sham mice by reducing inflammatory osteoclastogenesis. This beneficial impact of textitSb is mediated by the regulation of the inflammatory environment required for the generation of inflammatory osteoclasts. We also showed that textitSb derivatives as well as agonists of Tlr2, Dectin-1, and Mincle specifically inhibited directly the differentiation of inflammatory but not steady-state osteoclasts in vitro. These findings demonstrate a preferential use of the PRR-associated costimulatory differentiation pathway by inflammatory osteoclasts, thus enabling their specific inhibition, which opens new therapeutic perspectives for inflammatory bone loss.},
keywords = {osteoclast, osteoimmunology, osteoporosis, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{SAUMONNEAU2023101335,
title = {Disruption of Botryococcus braunii colonies by glycoside hydrolases},
author = {Amélie Saumonneau and Nathan Lagneau and Lydia Awuor Ogonda and Catherine Dupré and Stéphanie Dutertre and Dominique Grizeau and Charles Tellier and Cyrille Grandjean and Franck Daligault},
url = {https://www.sciencedirect.com/science/article/pii/S2589014X23000063
hal-03973352v1 },
doi = {10.1016/j.biteb.2023.101335},
issn = {2589-014X},
year  = {2023},
date = {2023-01-13},
urldate = {2023-01-13},
journal = {Bioresource Technology Reports},
volume = {21},
pages = {101335},
abstract = {Microalgae are a promising alternative resource to fossil-based products. Botryococcus braunii is a colonial green microalga having the ability to convert CO2 by photosynthesis into long chain hydrocarbons. These are excreted and trapped in an extracellular matrix (ECM). A panel of glycosidases ranging from arabinanase, galactananase to endoglucanase was tested for their ability to lyse the polysaccharides maintaining the B. braunii colony integrity in order to release the hydrocarbons present in the extracellular matrix without harming the cells. The BpGH9 endoglucanase from Bacillus pumilus was fused with CtCBM3a from Clostridium thermocellum and yellow fluorescent protein to probe the presence of microcrystalline cellulose in the cell wall of B. braunii and to increase the efficacy of the endoglucanase. All the tested enzymes were able to some extent to dissociate the cells from the extracellular matrix while keeping them alive, suggesting the feasibility of a semi-continuous in situ recovery of hydrocarbons.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{ijms24021051,
title = {The Histone Chaperone Network Is Highly Conserved in Physarum polycephalum},
author = {Axel Poulet and Ellyn Rousselot and Stéphane Téletchéa and Céline Noirot and Yannick Jacob and Josien Wolfswinkel and Christophe Thiriet and Céline Duc},
url = {https://www.mdpi.com/1422-0067/24/2/1051
 hal-03978828v1 },
doi = {10.3390/ijms24021051},
issn = {1422-0067},
year  = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {International Journal of Molecular Sciences},
volume = {24},
number = {2},
abstract = {The nucleosome is composed of histones and DNA. Prior to their deposition on chromatin, histones are shielded by specialized and diverse proteins known as histone chaperones. They escort histones during their entire cellular life and ensure their proper incorporation in chromatin. Physarum polycephalum is a Mycetozoan, a clade located at the crown of the eukaryotic tree. We previously found that histones, which are highly conserved between plants and animals, are also highly conserved in Physarum. However, histone chaperones differ significantly between animal and plant kingdoms, and this thus probed us to further study the conservation of histone chaperones in Physarum and their evolution relative to animal and plants. Most of the known histone chaperones and their functional domains are conserved as well as key residues required for histone and chaperone interactions. Physarum is divergent from yeast, plants and animals, but PpHIRA, PpCABIN1 and PpSPT6 are similar in structure to plant orthologues. PpFACT is closely related to the yeast complex, and the Physarum genome encodes the animal-specific APFL chaperone. Furthermore, we performed RNA sequencing to monitor chaperone expression during the cell cycle and uncovered two distinct patterns during S-phase. In summary, our study demonstrates the conserved role of histone chaperones in handling histones in an early-branching eukaryote.},
keywords = {team 1, team 5},
pubstate = {published},
tppubtype = {article}
}
@article{cancers15041304,
title = {A Simple 3D Cell Culture Method for Studying the Interactions between Human Mesenchymal Stromal/Stem Cells and Patients Derived Glioblastoma},
author = {Lisa Oliver and Arturo Álvarez-Arenas and Céline Salaud and Juan Jiménez-Sanchez and Gabriel F. Calvo and Juan Belmonte-Beitia and Stephanie Blandin and Luciano Vidal and Victor Pérez and Dominique Heymann and François M. Vallette},
url = {https://www.mdpi.com/2072-6694/15/4/1304
 inserm-04001934v1 },
doi = {10.3390/cancers15041304},
issn = {2072-6694},
year  = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Cancers},
volume = {15},
number = {4},
abstract = {We have developed a 3D biosphere model using patient-derived cells (PDCs) from glioblastoma (GBM), the major form of primary brain tumors in adult, plus cancer-activated fibroblasts (CAFs), obtained by culturing mesenchymal stem cells with GBM conditioned media. The effect of MSC/CAFs on the proliferation, cell-cell interactions, and response to treatment of PDCs was evaluated. Proliferation in the presence of CAFs was statistically lower but the spheroids formed within the 3D-biosphere were larger. A treatment for 5 days with Temozolomide (TMZ) and irradiation, the standard therapy for GBM, had a marked effect on cell number in monocultures compared to co-cultures and influenced cancer stem cells composition, similar to that observed in GBM patients. Mathematical analyses of spheroids growth and morphology confirm the similarity with GBM patients. We, thus, provide a simple and reproducible method to obtain 3D cultures from patient-derived biopsies and co-cultures with MSC with a near 100% success. This method provides the basis for relevant in vitro functional models for a better comprehension of the role of tumor microenvironment and, for precision and/or personalized medicine, potentially to predict the response to treatments for each GBM patient.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{biom13040636,
title = {Engineering of a Bispecific Nanofitin with Immune Checkpoint Inhibitory Activity Conditioned by the Cross-Arm Binding to EGFR and PDL1},
author = {Perrine Jacquot and Javier Muñoz-Garcia and Maurine Fleury and Denis Cochonneau and Rémi Gaussin and Elise Enouf and Caroline Roze and Emilie Ollivier and Mathieu Cinier and Dominique Heymann},
url = {https://www.mdpi.com/2218-273X/13/4/636
 inserm-04056943v1 },
doi = {10.3390/biom13040636},
issn = {2218-273X},
year  = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Biomolecules},
volume = {13},
number = {4},
abstract = {Re-education of the tumor microenvironment with immune checkpoint inhibitors (ICI) has provided the most significant advancement in cancer management, with impressive efficacy and durable response reported. However, low response rates and a high frequency of immune-related adverse events (irAEs) remain associated with ICI therapies. The latter can be linked to their high affinity and avidity for their target that fosters on-target/off-tumor binding and subsequent breaking of immune self-tolerance in normal tissues. Many multispecific protein formats have been proposed to increase the tumor cell&#039;s selectivity of ICI therapies. In this study, we explored the engineering of a bispecific Nanofitin by the fusion of an anti-epidermal growth factor receptor (EGFR) and anti-programmed cell death ligand 1 (PDL1) Nanofitin modules. While lowering the affinity of the Nanofitin modules for their respective target, the fusion enables the simultaneous engagement of EGFR and PDL1, which translates into a selective binding to tumor cells co-expressing EGFR and PDL1 only. We demonstrated that affinity-attenuated bispecific Nanofitin could elicit PDL1 blockade exclusively in an EGFR-directed manner. Overall, the data collected highlight the potential of this approach to enhance the selectivity and safety of PDL1 checkpoint inhibition.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{MAM2023125422,
title = {Influence of pH on indole-dependent heterodimeric interactions between Anopheles gambiae odorant-binding proteins OBP1 and OBP4},
author = {Bhavika Mam and Katerina E. Tsitsanou and Panagiota G. V. Liggri and Francesca Saitta and Evgenia C. V. Stamati and Jarjapu Mahita and Georgios Leonis and Christina E. Drakou and Manthos Papadopoulos and Philippe Arnaud and Bernard Offmann and Dimitrios Fessas and Ramanathan Sowdhamini and Spyros E. Zographos},
url = {https://www.sciencedirect.com/science/article/pii/S0141813023023164},
doi = {https://doi.org/10.1016/j.ijbiomac.2023.125422},
issn = {0141-8130},
year  = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {International Journal of Biological Macromolecules},
volume = {245},
pages = {125422},
abstract = {Insect Odorant Binding Proteins (OBPs) constitute important components of their olfactory apparatus, as they are essential for odor recognition. OBPs undergo conformational changes upon pH change, altering their interactions with odorants. Moreover, they can form heterodimers with novel binding characteristics. Anopheles gambiae OBP1 and OBP4 were found capable of forming heterodimers possibly involved in the specific perception of the attractant indole. In order to understand how these OBPs interact in the presence of indole and to investigate the likelihood of a pH-dependent heterodimerization mechanism, the crystal structures of OBP4 at pH 4.6 and 8.5 were determined. Structural comparison to each other and with the OBP4-indole complex (3Q8I, pH 6.85) revealed a flexible N-terminus and conformational changes in the α4-loop-α5 region at acidic pH. Fluorescence competition assays showed a weak binding of indole to OBP4 that becomes further impaired at acidic pH. Additional Molecular Dynamic and Differential Scanning Calorimetry studies displayed that the influence of pH on OBP4 stability is significant compared to the modest effect of indole. Furthermore, OBP1-OBP4 heterodimeric models were generated at pH 4.5, 6.5, and 8.5, and compared concerning their interface energy and cross-correlated motions in the absence and presence of indole. The results indicate that the increase in pH may induce the stabilization of OBP4 by increasing its helicity, thereby enabling indole binding at neutral pH that further stabilizes the protein and possibly promotes the creation of a binding site for OBP1. A decrease in interface stability and loss of correlated motions upon transition to acidic pH may provoke the heterodimeric dissociation allowing indole release. Finally, we propose a potential OBP1-OBP4 heterodimer formation/disruption mechanism induced by pH change and indole binding.},
keywords = {Heterodimer, Indole, Insect olfaction, Interface energetics, Molecular dynamics, Mosquito, OBP, Odorant binding protein, pH-dependence, Structure, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{&lt;LineBreak&gt;doi:10.1073/pnas.2305195120,
title = {Cooperation and cheating orchestrate Vibrio assemblages and polymicrobial synergy in oysters infected with OsHV-1 virus},
author = {Daniel Oyanedel and Arnaud Lagorce and Maxime Bruto and Philippe Haffner and Amandine Morot and Yannick Labreuche and Yann Dorant and Sébastien La Forest Divonne and François Delavat and Nicolas Inguimbert and Caroline Montagnani and Benjamin Morga and Eve Toulza and Cristian Chaparro and Jean-Michel Escoubas and Yannick Gueguen and Jeremie Vidal-Dupiol and Julien Lorgeril and Bruno Petton and Lionel Degremont and Delphine Tourbiez and Léa-Lou Pimparé and Marc Leroy and Océane Romatif and Juliette Pouzadoux and Guillaume Mitta and Frédérique Le Roux and Guillaume M. Charrière and Marie-Agnès Travers and Delphine Destoumieux-Garzón},
url = {https://www.pnas.org/doi/abs/10.1073/pnas.2305195120
https://www.biorxiv.org/content/early/2023/02/11/2023.02.11.528104},
doi = {10.1073/pnas.2305195120},
year  = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Proceedings of the National Academy of Sciences},
volume = {120},
number = {40},
pages = {e2305195120},
abstract = {Polymicrobial infections threaten the health of humans and animals but remain understudied in natural systems. We recently described the Pacific Oyster Mortality Syndrome (POMS), a polymicrobial disease affecting oyster production worldwide. In the French Atlantic coast, the disease involves coinfection with ostreid herpesvirus 1 (OsHV-1) and virulent Vibrio. However, it is unknown whether consistent Vibrio populations are associated with POMS in different regions, how Vibrio contribute to POMS, and how they interact with OsHV-1 during pathogenesis. By connecting field-based approaches in a Mediterranean ecosystem, laboratory infection assays and functional genomics, we uncovered a web of interdependencies that shape the structure and function of the POMS pathobiota. We show that Vibrio harveyi and Vibrio rotiferianus are predominant in OsHV-1-diseased oysters and that OsHV-1 drives the partition of the Vibrio community observed in the field. However only V. harveyi synergizes with OsHV-1 by promoting mutual growth and accelerating oyster death. V. harveyi shows high-virulence potential and dampens oyster cellular defenses through a type 3 secretion system, making oysters a more favorable niche for microbe colonization. In addition, V. harveyi produces a key siderophore called vibrioferrin. This important resource promotes the growth of V. rotiferianus, which cooccurs with V. harveyi in diseased oysters, and behaves as a cheater by benefiting from V. harveyi metabolite sharing. Our data show that cooperative behaviors contribute to synergy between bacterial and viral coinfecting partners. Additional cheating behaviors further shape the polymicrobial consortium. Controlling cooperative behaviors or countering their effects opens avenues for mitigating polymicrobial diseases.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{pmid37869710,
title = {Technical report: liquid overlay technique allows the generation of homogeneous osteosarcoma, glioblastoma, lung and prostate adenocarcinoma spheroids that can be used for drug cytotoxicity measurements},
author = {Camille Jubelin and Javier Muñoz-Garcia and Denis Cochonneau and Emilie Ollivier and François Vallette and Marie-Françoise Heymann and Lisa Oliver and Dominique Heymann},
url = { inserm-04501811v1 },
doi = {10.3389/fbioe.2023.1260049},
issn = {2296-4185},
year  = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Front Bioeng Biotechnol},
volume = {11},
pages = {1260049},
abstract = { The mechanisms involved in cancer initiation, progression, drug resistance, and disease recurrence are traditionally investigated through  adherent monolayer (2D) cell models. However, solid malignant tumor growth is characterized by progression in three dimensions (3D), and an increasing amount of evidence suggests that 3D culture models, such as spheroids, are suitable for mimicking cancer development. The aim of this report was to reaffirm the relevance of simpler 3D culture methods to produce highly reproducible spheroids, especially in the context of drug cytotoxicity measurements.  Human A549 lung adenocarcinoma, LnCaP prostate adenocarcinoma, MNNG/HOS osteosarcoma and U251 glioblastoma cell lines were grown into spheroids for 20 days using either Liquid Overlay Technique (LOT) or Hanging Drop (HD) in various culture plates. Their morphology was examined by microscopy. Sensitivity to doxorubicin was compared between MNNG/HOS cells grown in 2D and 3D.  For all cell lines studied, the morphology of spheroids generated in round-bottom multiwell plates was more repeatable than that of those generated in flat-bottom multiwell plates. HD had no significant advantage over LOT when the spheroids were cultured in round-bottom plates. Finally, the IC of doxorubicin on MNNG/HOS cultured in 3D was 18.8 times higher than in 2D cultures (3D IC = 15.07 ± 0.3 µM; 2D IC = 0.8 ± 0.4 µM; * &lt; 0.05).  In conclusion, we propose that the LOT method, despite and because of its simplicity, is a relevant 3D model for drug response measurements that could be scaled up for high throughput screening.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{pmid36114125,
title = {The ecologically relevant genetics of plant-plant interactions},
author = { and Claude Becker and Richard Berthomé and Philippe Delavault and Timothée Flutre and Hélène Fréville and Stéphanie Gibot-Leclerc and Valérie Le Corre and Jean-Benoit Morel and Nathalie Moutier and Stéphane Muños and Céline Richard-Molard and James Westwood and Pierre-Emmanuel Courty and Alexandre de Saint Germain and Gaëtan Louarn and Fabrice Roux},
url = {hal-03800896v1 },
doi = {10.1016/j.tplants.2022.08.014},
issn = {1878-4372},
year  = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Trends Plant Sci},
volume = {28},
number = {1},
pages = {31--42},
abstract = {Interactions among plants have been long recognized as a major force driving plant community dynamics and crop yield. Surprisingly, our knowledge of the ecological genetics associated with variation of plant-plant interactions remains limited. In this opinion article by scientists from complementary disciplines, the international PLANTCOM network identified four timely questions to foster a better understanding of the mechanisms mediating plant assemblages. We propose that by identifying the key relationships among phenotypic traits involved in plant-plant interactions and the underlying adaptive genetic and molecular pathways, while considering environmental fluctuations at diverse spatial and time scales, we can improve predictions of genotype-by-genotype-by-environment interactions and modeling of productive and stable plant assemblages in wild habitats and crop fields.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@mastersthesis{chalopin2022,
title = {Caractérisation des cellules tumorales circulantes de sarcomes osseux : identification de nouveaux marqueurs de la pathologie recidivante},
author = {Antoine CHALOPIN},
url = {https://theses.hal.science/tel-03937416},
year  = {2022},
date = {2022-12-20},
urldate = {2022-12-20},
keywords = {team 3, thesis},
pubstate = {published},
tppubtype = {mastersthesis}
}
@article{martinez2022soil,
title = {Soil microbiota promotes early developmental stages of Phelipanche ramosa L. Pomel during plant parasitism on Brassica napus L.},
author = {Lisa Martinez and Jean-Bernard Pouvreau and Gregory Montiel and Christophe Jestin and Philippe Delavault and Philippe Simier and Lucie Poulin},
url = {https://nantes-universite.hal.science/hal-04370677v1 },
doi = {https://doi.org/10.1007/s11104-022-05822-6},
year  = {2022},
date = {2022-12-08},
urldate = {2022-12-08},
journal = {Plant and Soil},
volume = {483},
pages = {667–691 },
publisher = {Springer},
abstract = {Purpose
The root holoparasitic plant Phelipanche ramosa has become a major constraint for rapeseed cultivation in western France for the last decades and its control remains challenging. To date, few studies have considered soil microbiota as a third partner of the parasitic plant-plant interaction. Therefore, we here addressed the question of how soil microbiota interferes with host-derived signal metabolites required for host plant recognition by the parasitic plant.

Methods
Using a branched broomrape infested soil (genetic group 1) from a rapeseed field, we first provided soil physicochemical and microbiological descriptions by metabarcoding, followed by P. ramosa seed germination and prehaustorium formation bioassays, and by in vitro co-cultivation with Brassica napus.

Results
Co-cultivation in presence of soil microorganisms promoted parasitic plant seed germination and attachments to host’s roots. Seed germination assays showed that only the combination of gluconasturtiin (main rapeseed glucosinolate) with soil extracts stimulated broomrape germination. This suggests a microbial conversion of gluconasturtiin into germination stimulants via soil microbial myrosinase enzymes. Furthermore, soil bacteria Arthrobacter, Ralstonia, Actinobacterium, Proteobacterium spp. and fungus Penicillium spp. were isolated and screened for myrosinase activity. Pre-germinated seeds treated with soil extracts or differentially filtrated soil extracts also promoted the formation of P. ramosa prehaustorium and led to more parasitic attachments on rapeseed roots in co-cultivation assays. This thus suggests that this enhancement of parasitic attachments could also be partly attributed to soil microbial production of haustorium inducing factors.

Conclusion
Soil microbiota influences B. napus - P. ramosa interaction by altering direct and indirect recognition signals.},
keywords = {team 4, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{joublindelavat_genetic_2022,
title = {Genetic and physiological insights into the diazotrophic activity of a non-cyanobacterial marine diazotroph},
author = {Aurélie Joublin-Delavat and Katia Touahri and Pauline Crétin and Amandine Morot and Sophie Rodrigues and Bruno Jesus and Florian Trigodet and François Delavat},
url = {https://onlinelibrary.wiley.com/doi/10.1111/1462-2920.16261
hal-03993957v1 },
doi = {10.1111/1462-2920.16261},
issn = {1462-2912, 1462-2920},
year  = {2022},
date = {2022-12-01},
urldate = {2022-12-01},
journal = {Environmental Microbiology},
volume = {24},
number = {12},
pages = {6510--6523},
abstract = {Nitrogen (N2) fixation, or diazotrophy, supports a large part of primary production in oceans. Culture-independent approaches highlighted the presence in abundance of marine non-cyanobacterial diazotrophs (NCD), but their ecophysiology remains elusive, mostly because of the low number of isolated NCD and because of the lack of available genetic tools for these isolates. Here, a dual genetic and functional approach allowed unveiling the ecophysiology of a marine NCD affiliated to the species Vibrio diazotrophicus. Physiological characterization of the first marine NCD mutant obtained so far was performed using a soft-gellan assay, demonstrating that a ΔnifH mutant is not able to grow in nitrogen-free media. Furthermore, we demonstrated that V. diazotrophicus produces a thick biofilm under diazotrophic conditions, suggesting biofilm production as an adaptive response of this NCD to cope with the inhibition of nitrogen fixation by molecular oxygen. Finally, the genomic signature of V. diazotrophicus is essentially absent from metagenomic data of Tara Ocean expeditions, despite having been isolated from various marine environments. We think that the genetically tractable V. diazotrophicus strain used in this study may serve as an ideal model to study the ecophysiology of these overlooked procaryotic group.},
keywords = {EDIPHIS, SMIDIDI, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{pmid36481668,
title = {Osteosarcoma},
author = {Hannah C Beird and Stefan S Bielack and Adrienne M Flanagan and Jonathan Gill and Dominique Heymann and Katherine A Janeway and J Andrew Livingston and Ryan D Roberts and Sandra J Strauss and Richard Gorlick},
url = {inserm-04502548v1 },
doi = {10.1038/s41572-022-00409-y},
issn = {2056-676X},
year  = {2022},
date = {2022-12-01},
urldate = {2022-12-01},
journal = {Nat Rev Dis Primers},
volume = {8},
number = {1},
pages = {77},
abstract = {Osteosarcoma is the most common primary malignant tumour of the bone. Osteosarcoma incidence is bimodal, peaking at 18 and 60 years of age, and is slightly more common in males. The key pathophysiological mechanism involves several possible genetic drivers of disease linked to bone formation, causing malignant progression and metastasis. While there have been significant improvements in the outcome of patients with localized disease, with event-free survival outcomes exceeding 60%, in patients with metastatic disease, event-free survival outcomes remain poor at less than 30%. The suspicion of osteosarcoma based on radiographs still requires pathological evaluation of a bone biopsy specimen for definitive diagnosis and CT imaging of the chest should be performed to identify lung nodules. So far, population-based screening and surveillance strategies have not been implemented due to the rarity of osteosarcoma and the lack of reliable markers. Current screening focuses only on groups at high risk such as patients with genetic cancer predisposition syndromes. Management of osteosarcoma requires a multidisciplinary team of paediatric and medical oncologists, orthopaedic and general surgeons, pathologists, radiologists and specialist nurses. Survivors of osteosarcoma require specialized medical follow-up, as curative treatment consisting of chemotherapy and surgery has long-term adverse effects, which also affect the quality of life of patients. The development of osteosarcoma model systems and related research as well as the evaluation of new treatment approaches are ongoing to improve disease outcomes, especially for patients with metastases.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@conference{nokey,
title = {Reduction of radiotoxicity by ultra-high dose rate protontherapy in zebrafish embryos},
author = { Gaëlle Saade, Vincent Potiron, Stéphane Supiot },
url = {hal-03886413v1 },
year  = {2022},
date = {2022-10-05},
urldate = {2022-10-05},
keywords = {team 3},
pubstate = {published},
tppubtype = {conference}
}
@article{pmid35999162b,
title = {[Clinical research in radiation oncology: how to move from the laboratory to the patient?]},
author = {V Potiron and G Delpon and L Ollivier and L Vaugier and M Doré and V Guimas and E Rio and F Thillays and C Llagostera and A Moignier and S Josset and S Chiavassa and T Perennec and S Supiot},
url = {hal-03777900v1 },
doi = {10.1016/j.canrad.2022.07.009},
issn = {1769-6658},
year  = {2022},
date = {2022-10-01},
urldate = {2022-10-01},
journal = {Cancer Radiother},
volume = {26},
number = {6-7},
pages = {808--813},
abstract = {Translational research in radiation oncology is undergoing intense development. An increasingly rapid transfer is taking place from the laboratory to the patients, both in the selection of patients who can benefit from radiotherapy and in the development of innovative irradiation strategies or the development of combinations with drugs. Accelerating the passage of discoveries from the laboratory to the clinic represents the ideal of any translational research program but requires taking into account the multiple obstacles that can slow this progress. The ambition of the RadioTransNet network, a project to structure preclinical research in radiation oncology in France, is precisely to promote scientific and clinical interactions at the interface of radiotherapy and radiobiology, in its preclinical positioning, in order to identify priorities for strategic research dedicated to innovation in radiotherapy. The multidisciplinary radiotherapy teams with experts in biology, medicine, medical physics, mathematics and engineering sciences are able to meet these new challenges which will allow these advances to be made available to patients as quickly as possible.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{pmid35990515,
title = {Lipopolysaccharide-binding protein expression is associated to the metastatic status of osteosarcoma patients},
author = {Clément J F Heymann and Christine Bobin-Dubigeon and Javier Muñoz-Garcia and Denis Cochonneau and Emilie Ollivier and Marie-Françoise Heymann and Dominique Heymann},
url = {inserm-03746641v1 },
doi = {10.1016/j.jbo.2022.100451},
issn = {2212-1366},
year  = {2022},
date = {2022-10-01},
urldate = {2022-10-01},
journal = {J Bone Oncol},
volume = {36},
pages = {100451},
abstract = {Osteosarcoma (OS) is a rare malignant primary bone tumours characterized by a high genetic and cell composition heterogeneity. Unfortunately, despite the use of drug combinations and the recent development of immunotherapies, the overall survival has not improved in the last four decades. Due to the key role of the tumour microenvironment in the pathogenesis of OS, a better understanding of its microenvironment is mandatory to develop new therapeutic approaches. From retrospective biological cohorts of OS, we analysed by immunohistochemistry the presence of lipopolysaccharide (LPS)-binding protein (LBP) in diagnostic biopsies with local disease and compared their level of infiltration to patients suffering from metastatic status. LBP is considered as a marker of LPS exposure and can indirectly reflect the presence of Gram-negative microbiota. LBP were detected in the cytoplasm of OS cells as well as in tumour-associated macrophage. Tumour samples of patients with local disease were significantly enriched in LBP compared to tumour tissues of patients with metastatic status. Lung metastatic tissues showed similar level of LBP compared to paired primary tumours. Overall, this study strongly suggests the presence of Gram-negative bacteria in OS tissues and demonstrated their significant differential level according the metastatic status. This tumour-associated microbiome may help in the conceptualisation of new therapeutic approach to trigger efficient therapeutic responses against cancer.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@proceedings{pmid35908990,
title = {Adaptation of the tumour and its ecosystem to radiotherapies: Mechanisms, imaging and therapeutic approaches » XIVe édition du workshop organisé par le réseau « Vectorisation, Imagerie, Radiothérapies » du Cancéropôle Grand-Ouest, 22–25 septembre 2021, Le Bono, France},
author = {Françoise Léost and Grégory Delpon and Emmanuel Garcion and Jean-François Gestin and Mathieu Hatt and Vincent Potiron and Latifa Rbah-Vidal and Stéphane Supiot},
url = {hal-04511672v1 },
doi = {10.1016/j.bulcan.2022.06.005},
issn = {1769-6917},
year  = {2022},
date = {2022-10-01},
urldate = {2022-10-01},
journal = {Bull Cancer},
volume = {109},
number = {10},
pages = {1088--1093},
abstract = {The fourteenth edition of the workshop covered the latest advances in internal and external radiotherapy obtained through a better understanding of the adaptive capacity of the tumor and its microenvironment, from different disciplinary angles, chemistry, biology, physics, and medicine, paving the way for numerous technological innovations. The biological aspects and the contribution of imaging in monitoring and understanding the adaptation of tumors to radiotherapy were presented, before focusing on innovative radiotherapy strategies and machine learning and data-driven techniques. Finally, the challenges were explored in the radiobiology of targeted radionuclide therapy as well as data science and machine learning in radiomics.},
keywords = {team 3},
pubstate = {published},
tppubtype = {proceedings}
}
@conference{nokey,
title = {Microdosimetry and radiolytic species production in UHDR proton beam using GATE and Geant4-DNA},
author = {Giovanna Rosa Fois, Guillaume Blain, Sophie Chiavassa, Grégory Delpon, Manon Evin, Vincent Fiegel , Mohammad Ghalei , Ferid Haddad , S. Incerti , Charbel Koumeir, Vincent Métivier , Quentin Mouchard , Freddy Poirier , Vincent Potiron , Noël Servagent, Stéphane Supiot, Hoang Ngoc Tran , Johan Vandenborre , Lydia Maigne },
url = {hal-03886937v1 },
year  = {2022},
date = {2022-10-01},
urldate = {2022-10-01},
keywords = {team 3},
pubstate = {published},
tppubtype = {conference}
}
@article{pmid36176621,
title = {Design and validation of a tunable inertial microfluidic system for the efficient enrichment of circulating tumor cells in blood},
author = {Alejandro Rodríguez-Pena and Estibaliz Armendariz and Alvaro Oyarbide and Xabier Morales and Sergio Ortiz-Espinosa and Borja Ruiz-Fernández de Córdoba and Denis Cochonneau and Iñaki Cornago and Dominique Heymann and Josepmaría Argemi and Delia D&#039;Avola and Bruno Sangro and Fernando Lecanda and Ruben Pio and Iván Cortés-Domínguez and Carlos Ortiz-de-Solórzano},
url = {inserm-03659450v1 },
doi = {10.1002/btm2.10331},
issn = {2380-6761},
year  = {2022},
date = {2022-09-01},
urldate = {2022-09-01},
journal = {Bioeng Transl Med},
volume = {7},
number = {3},
pages = {e10331},
abstract = {The analysis of circulating tumor cells (CTCs) in blood is a powerful noninvasive alternative to conventional tumor biopsy. Inertial-based separation is a promising high-throughput, marker-free sorting strategy for the enrichment and isolation of CTCs. Here, we present and validate a double spiral microfluidic device that efficiently isolates CTCs with a fine-tunable cut-off value of 9 μm and a separation range of 2 μm. We designed the device based on computer simulations that introduce a novel, customized inertial force term, and provide practical fabrication guidelines. We validated the device using calibration beads, which allowed us to refine the simulations and redesign the device. Then we validated the redesigned device using blood samples and a murine model of metastatic breast cancer. Finally, as a proof of principle, we tested the device using peripheral blood from a patient with hepatocellular carcinoma, isolating more than 17 CTCs/ml, with purity/removal values of 96.03% and 99.99% of white blood cell and red blood cells, respectively. These results confirm highly efficient CTC isolation with a stringent cut-off value and better separation results than the state of the art.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{pmid36089610,
title = {Three-dimensional in vitro culture models in oncology research},
author = {Camille Jubelin and Javier Muñoz-Garcia and Laurent Griscom and Denis Cochonneau and Emilie Ollivier and Marie-Françoise Heymann and François M Vallette and Lisa Oliver and Dominique Heymann},
url = { hal-03798394v1 },
doi = {10.1186/s13578-022-00887-3},
issn = {2045-3701},
year  = {2022},
date = {2022-09-01},
urldate = {2022-09-01},
journal = {Cell Biosci},
volume = {12},
number = {1},
pages = {155},
abstract = {Cancer is a multifactorial disease that is responsible for 10 million deaths per year. The intra- and inter-heterogeneity of malignant tumors make it difficult to develop single targeted approaches. Similarly, their diversity requires various models to investigate the mechanisms involved in cancer initiation, progression, drug resistance and recurrence. Of the in vitro cell-based models, monolayer adherent (also known as 2D culture) cell cultures have been used for the longest time. However, it appears that they are often less appropriate than the three-dimensional (3D) cell culture approach for mimicking the biological behavior of tumor cells, in particular the mechanisms leading to therapeutic escape and drug resistance. Multicellular tumor spheroids are widely used to study cancers in 3D, and can be generated by a multiplicity of techniques, such as liquid-based and scaffold-based 3D cultures, microfluidics and bioprinting. Organoids are more complex 3D models than multicellular tumor spheroids because they are generated from stem cells isolated from patients and are considered as powerful tools to reproduce the disease development in vitro.  The present review provides an overview of the various 3D culture models that have been set up to study cancer development and drug response. The advantages of 3D models compared to 2D cell cultures, the  constraint, and the fields of application of these models and their techniques of production are also discussed.},
keywords = {team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Chandola2022.08.25.505241,
title = {Combined in vivo and in situ genome-resolved metagenomics reveals novel symbiotic nitrogen fixing interactions between non-cyanobacterial diazotrophs and microalgae},
author = {Udita Chandola and Camille Trottier and Marinna Gaudin and Erik Manirakiza and Samuel Menicot and Isabelle Louvet and Thomas Lacour and Timothée Chaumier and Atsuko Tanaka and Samuel Chaffron and Leila Tirichine},
url = {https://www.biorxiv.org/content/early/2022/08/25/2022.08.25.505241},
doi = {10.1101/2022.08.25.505241},
year  = {2022},
date = {2022-08-25},
urldate = {2022-08-25},
journal = {bioRxiv},
publisher = {Cold Spring Harbor Laboratory},
abstract = {Non-cyanobacteria diazotrophs (NCDs) were shown to dominate in surface waters shifting the long-held paradigm of cyanobacteria dominance and raising fundamental questions on how these putative heterotrophic bacteria thrive in sunlit oceans. Here, we report an unprecedented finding in the widely used model diatom Phaeodactylum triconrnutum (Pt) of NCDs sustaining diatom cells in the absence of bioavailable nitrogen. We identified PtNCDs using metagenomics sequencing and detected nitrogenase gene in silico and/or by PCR. We demonstrated nitrogen fixation in PtNCDs and their close genetic affiliation with NCDs from the environment. We showed the wide occurrence of this type of symbiosis with the isolation of NCDs from other microalgae and their identification in the environment and in co-occurrence with photosynthetic microalgae. Overall, this study provides evidence for a previously overlooked symbiosis using a multidisciplinary model-based approach which will consequently help understand the different players driving global marine nitrogen fixation.Competing Interest StatementThe authors have declared no competing interest.},
keywords = {team 5, thesis},
pubstate = {forthcoming},
tppubtype = {article}
}
@article{Wu2022.07.29.502047,
title = {PhaeoEpiView: An epigenome browser of the newly assembled genome of the model diatom Phaeodactylum tricornutum},
author = {Yue Wu and Chaumier Timothée and Eric Manirakiza and Alaguraj Veluchamy and Leila Tirichine},
url = {https://www.biorxiv.org/content/early/2022/08/01/2022.07.29.502047},
doi = {10.1101/2022.07.29.502047},
year  = {2022},
date = {2022-08-01},
urldate = {2022-01-01},
journal = {bioRxiv},
publisher = {Cold Spring Harbor Laboratory},
abstract = {Motivation Recent advances in DNA sequencing technologies in particular of long reads type greatly improved genomes assembly leading to discrepancies between both published annotations and epigenome tracks which did not keep pace with new assemblies. This comprises the availability of accurate resources which penalizes the progress in research.Results Here, we used the latest improved telomere to telomere assembly of the model pennate diatom Phaeodactylum tricornutum to lift over the gene models from Phatr3, a previously annotated reference genome. We used the lifted genome annotation including genes and transposable elements to map the epigenome landscape, namely DNA methylation and post translational modifications of histones providing the community with PhaeoEpiView, a browser that allows the visualization of epigenome data as well as transcripts on an updated reference genome to better understand the biological significance of the mapped data on contiguous genome rather than a fragmented one. We updated previously published histone marks with a more accurate mapping using monoclonal antibodies instead of polyclonal and deeper sequencing. PhaeoEpiView will be continuously updated with the newly published epigenomic data making it the largest and richest epigenome browser of any stramenopile. We expect that PhaeoEpiView will be a standard tool for the coming era of molecular environmental studies where epigenetics holds a place of choice.Availability PhaeoEpiView is available at: https://PhaeoEpiView.univ-nantes.frCompeting Interest StatementThe authors have declared no competing interest.},
keywords = {team 5},
pubstate = {forthcoming},
tppubtype = {article}
}
@article{pmid36077747,
title = {Abscopal Response in Metastatic Melanoma: Real-World Data of a Retrospective, Multicenter Study},
author = {Luc Ollivier and Charles Orione and Paul Bore and Laurent Misery and Delphine Legoupil and Jean-Christophe Leclere and Anne Coste and Gilles Girault and Iona Sicard-Cras and Clemence Kacperek and Francois Lucia and Dinu Stefan and François Thillays and Emmanuel Rio and Paul Lesueur and Christian Berthou and Dominique Heymann and Stéphane Champiat and Stéphane Supiot and Loig Vaugier and William Kao},
url = {inserm-03878079v1 },
doi = {10.3390/cancers14174213},
issn = {2072-6694},
year  = {2022},
date = {2022-08-01},
urldate = {2022-08-01},
journal = {Cancers (Basel)},
volume = {14},
number = {17},
abstract = {OBJECTIVE: To evaluate the incidence of the abscopal response (AR) in patients with metastatic melanoma requiring palliative radiotherapy (RT).

PATIENTS AND METHODS: Patients treated for metastatic melanoma between January 1998 and February 2020 in four oncology departments were screened. Patients with progression under immune checkpoint inhibitors or without ongoing systemic treatment, and requiring palliative RT were considered. The AR was defined as an objective response according to RECIST and/or iRECIST for at least one non-irradiated metastasis at distance (≥10 cm) from the irradiated lesion. Primary endpoint was the rate of AR. Secondary endpoints were overall survival (OS), progression-free survival (PFS), local control (LC) of the irradiated lesion, and toxicity as assessed by CTCAE v5.

RESULTS: Over the period considered, 118 patients were included and analyzed. Fifteen patients (12.7%) had an AR. With a median follow-up of 7.7 months (range, 0.2-242.2), median OS and PFS after RT were significantly longer in patients with an AR compared to those without: 28 vs. 6.6 months ( &lt; 0.01) and not reached vs. .2 months, respectively. No grade ≥2 toxicity was reported. Patients who developed an AR were more likely to be treated with immunotherapy (93.3% vs. 55.9%,  0.02). In multivariate analysis, they had a higher number of irradiated metastases treated concomitantly (HR = 16.9,  &lt; 0.01) and a higher rate of mild infections during RT (HR = 403.5,  &lt; 0.01).

CONCLUSIONS: AR in metastatic melanoma seems to be highly prognostic of overall survival, although it is a rare phenomenon. It may be promoted by multiple concomitant treatments with RT and immunotherapy and by acute inflammatory events such as infection.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{pmid35776904,
title = {Noncanonical Strigolactone Analogues Highlight Selectivity for Stimulating Germination in Two  Populations},
author = {Suzanne Daignan Fornier and Alexandre de Saint Germain and Pascal Retailleau and Jean-Paul Pillot and Quentin Taulera and Lucile Andna and Laurence Miesch and Soizic Rochange and Jean-Bernard Pouvreau and François-Didier Boyer},
url = {hal-03712428v1 },
doi = {10.1021/acs.jnatprod.2c00282},
issn = {1520-6025},
year  = {2022},
date = {2022-08-01},
urldate = {2022-08-01},
journal = {J Nat Prod},
volume = {85},
number = {8},
pages = {1976--1992},
abstract = {Strigolactones (SLs) are plant hormones exuded in the rhizosphere with a signaling role for the development of arbuscular mycorrhizal (AM) fungi and as stimulants of seed germination of the parasitic weeds , , and , the most threatening weeds of major crops worldwide.  is present mainly on rape, hemp, and tobacco in France.  2a preferentially attacks hemp, while  1 attacks rapeseed. The recently isolated cannalactone () from hemp root exudates has been characterized as a noncanonical SL that selectively stimulates the germination of  2a seeds in comparison with  1. In the present work, (-)-solanacol (), a canonical orobanchol-type SL exuded by tobacco and tomato, was established to possess a remarkable selective germination stimulant activity for  2a seeds. Two cannalactone analogues, named (±)-SdL19 and (±)-SdL118, have been synthesized. They have an unsaturated acyclic carbon chain with a tertiary hydroxy group and a methyl or a cyclopropyl group instead of a cyclohexane A-ring, respectively. (±)-SdL analogues are able to selectively stimulate  2a, revealing that these minimal structural elements are key for this selective bioactivity. In addition, (±)-SdL19 is able to inhibit shoot branching in  and  and induces hyphal branching in the AM fungus , like SLs.},
keywords = {HEMPT_iT, team 4},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1128/aac.00083-22,
title = {Selection of Bis-Indolyl Pyridines and Triphenylamines as New Inhibitors of SARS-CoV-2 Cellular Entry by Modulating the Spike Protein/ACE2 Interfaces},
author = {Delphine Lapaillerie and Cathy Charlier and Véronique Guyonnet-Dupérat and Emilie Murigneux and Henrique S. Fernandes and Fábio G. Martins and Rita P. Magalhães and Tatiana F. Vieira and Clémence Richetta and Frédéric Subra and Samuel Lebourgeois and Charlotte Charpentier and Diane Descamps and Benoît Visseaux and Pierre Weigel and Alexandre Favereaux and Claire Beauvineau and Frédéric Buron and Marie-Paule Teulade-Fichou and Sylvain Routier and Sarah Gallois-Montbrun and Laurent Meertens and Olivier Delelis and Sérgio F. Sousa and Vincent Parissi},
url = {https://journals.asm.org/doi/abs/10.1128/aac.00083-22
hal-03826873v1 },
doi = {10.1128/aac.00083-22},
year  = {2022},
date = {2022-07-05},
urldate = {2022-07-05},
journal = {Antimicrobial Agents and Chemotherapy},
volume = {0},
number = {0},
pages = {e00083-22},
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent that has caused the current coronavirus disease (COVID) pandemic. Viral infection relies on the viral S (spike) protein/cellular receptor ACE2 interaction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent that has caused the current coronavirus disease (COVID) pandemic. Viral infection relies on the viral S (spike) protein/cellular receptor ACE2 interaction. Disrupting this interaction would lead to early blockage of viral replication. To identify chemical tools to further study these functional interfaces, 139,146 compounds from different chemical libraries were screened through an S/ACE2 in silico virtual molecular model. The best compounds were selected for further characterization using both cellular and biochemical approaches, reiterating SARS-CoV-2 entry and the S/ACE2 interaction. We report here two selected hits, bis-indolyl pyridine AB-00011778 and triphenylamine AB-00047476. Both of these compounds can block the infectivity of lentiviral vectors pseudotyped with the SARS-CoV-2 S protein as well as wild-type and circulating variant SARS-CoV-2 strains in various human cell lines, including pulmonary cells naturally susceptible to infection. AlphaLISA and biolayer interferometry confirmed a direct inhibitory effect of these drugs on the S/ACE2 association. A specific study of the AB-00011778 inhibitory properties showed that this drug inhibits viral replication with a 50% effective concentration (EC50) between 0.1 and 0.5 μM depending on the cell lines. Molecular docking calculations of the interaction parameters of the molecules within the S/ACE2 complex from both wild-type and circulating variants of the virus showed that the molecules may target multiple sites within the S/ACE2 interface. Our work indicates that AB-00011778 constitutes a good tool for modulating this interface and a strong lead compound for further therapeutic purposes.},
keywords = {impact},
pubstate = {published},
tppubtype = {article}
}
@article{pmid35703399,
title = {Tailoring the NIR-II Photoluminescence of Single Thiolated Au Nanoclusters by Selective Binding to Proteins},
author = {Franck Bertorelle and K David Wegner and Martina Perić Bakulić and Hussein Fakhouri and Clothilde Comby-Zerbino and Amin Sagar and Pau Bernadó and Ute Resch-Genger and Vlasta Bonačić-Koutecký and Xavier Le Guével and Rodolphe Antoine},
url = {hal-03740182v1 },
doi = {10.1002/chem.202200570},
issn = {1521-3765},
year  = {2022},
date = {2022-07-01},
urldate = {2022-07-01},
journal = {Chemistry},
volume = {28},
number = {39},
pages = {e202200570},
abstract = {Atomically precise gold nanoclusters are a fascinating class of nanomaterials that exhibit molecule-like properties and have outstanding photoluminescence (PL). Their ultrasmall size, molecular chemistry, and biocompatibility make them extremely appealing for selective biomolecule labeling in investigations of biological mechanisms at the cellular and anatomical levels. In this work, we report a simple route to incorporate a preformed Au nanocluster into a model bovine serum albumin (BSA) protein. A new approach combining small-angle X-ray scattering and molecular modeling provides a clear localization of a single Au within the protein to a cysteine residue on the gold nanocluster surface. Attaching Au to BSA strikingly modifies the PL properties with enhancement and a redshift in the second near-infrared (NIR-II) window. This study paves the way to conrol the design of selective sensitive probes in biomolecules through a ligand-based strategy to enable the optical detection of biomolecules in a cellular environment by live imaging.},
keywords = {team 2, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{doi.org/10.1371/journal.pgen.1010286,
title = {A bistable prokaryotic differentiation system underlying development of conjugative transfer competence},
author = {Sandra Sulser and Andrea Vucicevic and Veronica Bellini and Roxane Moritz and François Delavat and Vladimir Sentchilo and Nicolas Carraro and Jan Roelof van der Meer},
url = {hal-04202182v1 },
doi = {10.1371/journal.pgen.1010286},
year  = {2022},
date = {2022-06-28},
urldate = {2022-06-28},
journal = {Plos Genetics},
volume = {18},
issue = {6},
pages = {e1010286},
abstract = {The mechanisms and impact of horizontal gene transfer processes to distribute gene functions with potential adaptive benefit among prokaryotes have been well documented. In contrast, little is known about the life-style of mobile elements mediating horizontal gene transfer, whereas this is the ultimate determinant for their transfer fitness. Here, we investigate the life-style of an integrative and conjugative element (ICE) within the genus Pseudomonas that is a model for a widespread family transmitting genes for xenobiotic compound metabolism and antibiotic resistances. Previous work showed bimodal ICE activation, but by using single cell time-lapse microscopy coupled to combinations of chromosomally integrated single copy ICE promoter-driven fluorescence reporters, RNA sequencing and mutant analysis, we now describe the complete regulon leading to the arisal of differentiated dedicated transfer competent cells. The regulon encompasses at least three regulatory nodes and five (possibly six) further conserved gene clusters on the ICE that all become expressed under stationary phase conditions. Time-lapse microscopy indicated expression of two regulatory nodes (i.e., bisR and alpA-bisDC) to precede that of the other clusters. Notably, expression of all clusters except of bisR was confined to the same cell subpopulation, and was dependent on the same key ICE regulatory factors. The ICE thus only transfers from a small fraction of cells in a population, with an estimated proportion of between 1.7-4%, which express various components of a dedicated transfer competence program imposed by the ICE, and form the centerpiece of ICE conjugation. The components mediating transfer competence are widely conserved, underscoring their selected fitness for efficient transfer of this class of mobile elements.},
keywords = {Algae, team 5},
pubstate = {published},
tppubtype = {article}
}
@inbook{jubelin2022circulating,
title = {Circulating Tumor Cells and ctDNA in Sarcomas},
author = {Camille Jubelin and Denis Cochonneau and Emilie Moranton and Javier Munoz-Garcia and Dominique Heymann},
editor = {Stanley P. Leong and S. David Nathanson and Jonathan S. Zager},
doi = {10.1007/978-3-030-93084-4_12},
year  = {2022},
date = {2022-06-25},
urldate = {2022-06-25},
booktitle = {Cancer Metastasis Through the Lymphovascular System},
pages = {121--128},
publisher = {Springer},
abstract = {Sarcomas are clustered in two oncological entities named bone and soft tissue sarcomas. Both are rare cancers originating from the mesenchyme, characterized by their propensity to induce the development of lung metastases. Sarcoma cells escaping from the primary tumor site spread to the pulmonary tissue through the bloodstream where they found a favorable microenvironment to establish metastatic foci. The low number of patients, the high histological, genetic, and molecular heterogeneity of sarcomas combined with the absence of specific markers expressed by cancer cells make the detection and follow-up of the minimal residual disease challenging. Over the last decade, tremendous technological progress has been made towards the detection of recurrent diseases. The literature is now enriched of information describing the use of liquid biopsies in clinical care of sarcoma patients. This chapter aims to give a brief overview of the most recent data available on the detection of circulating tumor cells and circulating tumor DNA in sarcomas.},
keywords = {team 3, thesis},
pubstate = {published},
tppubtype = {inbook}
}
@conference{nokey,
title = {Hydrogen peroxide formation to investigate the radiolytic ROS production mechanism under proton FLASH conditions},
author = { Vincent Fiegel , Guillaume Blain , Manon Evin , Quentin Mouchard , Charbel Koumeir, Noël Servagent , Mohammad Ghalei , Giovanna Rosa Fois , Vincent Métivier, Freddy Poirier , Vincent Potiron , Stéphane Supiot , Ferid Haddad , Grégory Delpon , Sophie Chiavassa , Johan Vandenborre , Lydia Maigne },
url = { hal-03963165v1 },
year  = {2022},
date = {2022-06-15},
urldate = {2022-06-15},
keywords = {team 3},
pubstate = {published},
tppubtype = {conference}
}
@article{schimith2022polydatin,
title = {Polydatin as a therapeutic alternative for central nervous system disorders: A systematic review of animal studies},
author = {Lucia E Schimith and Michele G Dos Santos and Bruno D Arbo and Corinne André-Miral and Ana L Muccillo-Baisch and Mariana A Hort},
url = {https://onlinelibrary.wiley.com/doi/10.1002/ptr.7497},
doi = {10.1002/ptr.7497},
year  = {2022},
date = {2022-05-25},
urldate = {2022-05-25},
journal = {Phytotherapy Research},
volume = {36},
number = {7},
pages = {2852--2877},
publisher = {Wiley Online Library},
abstract = {Polydatin, or piceid, is a natural stilbene found in grapes, peanuts, and wines. Polydatin presents pharmacological activities, including neuroprotective properties, exerting preventive and/or therapeutic effects in central nervous system (CNS) disorders. In the present study, we summarize and discuss the neuroprotective effects of polydatin in CNS disorders and related pathological conditions in preclinical animal studies. A systematic review was performed by searching online databases, returning a total of 110 records, where 27 articles were selected and discussed here. The included studies showed neuroprotective effects of polydatin in experimental models of neurological disorders, including cerebrovascular disorders, Parkinson&#039;s disease, traumatic brain injuries, diabetic neuropathy, glioblastoma, and neurotoxicity induced by chemical agents. Most studies were focused on stroke (22.2%) and conducted in male rodents. The intervention protocol with polydatin was mainly acute (66.7%), with postdamage induction treatment being the most commonly used regimen (55.2%). Overall, polydatin ameliorated behavioral dysfunctions and/or promoted neurological function by virtue of its antioxidant and antiinflammatory properties. In summary, this review offers important scientific evidence for the neuroprotective effects and distinct pharmacological mechanisms of polydatin that not only enhances the present understanding but is also useful for the development of future preclinical and clinical investigations.},
keywords = {Funregiox, team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@inbook{Zhao2022,
title = {Epigenetic Control of Diatom Genomes: An Overview from In Silico Characterization to Functional Studies},
author = {Xue Zhao and Antoine Hoguin and Timothée Chaumier and Leila Tirichine},
editor = {Angela Falciatore and Thomas Mock},
url = {https://doi.org/10.1007/978-3-030-92499-7_7},
doi = {10.1007/978-3-030-92499-7_7},
isbn = {978-3-030-92499-7},
year  = {2022},
date = {2022-05-12},
urldate = {2022-01-01},
booktitle = {The Molecular Life of Diatoms},
pages = {179--202},
publisher = {Springer International Publishing},
address = {Cham},
abstract = {Epigenetics and its role in genome regulation is one of the most exciting areas of modern science. After a brief history of epigenetics and an introduction to the molecular basics of this discipline of science, this chapter describes the current knowledge of epigenetic components in diatoms, namely writers and erasers of DNA methylation and histone modifications. With a particular focus on the model pennate diatom Phaeodactylum tricornutum, we describe our current understanding of the contribution of few epigenetic factors to diatoms biology. Further, short regulatory non-coding RNAs (ncRNAs) as well as long ncRNAs are described in light of recent research. We highlight future studies and directions with a focus on epigenomic editing and environmental epigenetics.},
keywords = {team 5},
pubstate = {published},
tppubtype = {inbook}
}
@article{pmid35086922,
title = {Tumor ENPP1(CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer},
author = {Borja Ruiz-Fernandez de Cordoba and Haritz Moreno and Karmele Valencia and Naiara Perurena and Pablo Ruedas and Thomas Walle and Alberto Pezonaga-Torres and Juan Hinojosa and Elisabet Guruceaga and Antonio Pineda-Lucena and Marta Abengozar-Muela and Denis Cochonneau and Carolina Zandueta and Susana Martinez-Canarias and Alvaro Teijeira and Daniel Ajona and Sergio Ortiz-Espinosa and Xabier Morales and Carlos Ortiz de Solorzano and Marta Santisteban and Luis I Ramos-Garcia and Laura Guembe and Vratislav Strnad and Dominique Heymann and Sandra Hervas-Stubbs and Ruben Pio and Maria E Rodriguez-Ruiz and Carlos E de Andrea and Silvestre Vicent and Ignacio Melero and Fernando Lecanda and Rafael Martinez-Monge},
url = {https://pubmed.ncbi.nlm.nih.gov/35086922/
 hal-03550024v1 },
doi = {10.1158/2159-8290.CD-21-0932},
issn = {2159-8290},
year  = {2022},
date = {2022-05-01},
urldate = {2022-05-01},
journal = {Cancer Discov},
volume = {12},
number = {5},
pages = {1356-1377},
abstract = {Locoregional failure (LRF) in breast cancer patients post-surgery and post-irradiation (IR) is linked to a dismal prognosis. In a refined new model, we identified Enpp1 (Ectonucleotide pyrophosphatase /phosphodiesterase 1/CD203a) to be closely associated with LRF. Enpp1high circulating tumor cells (CTC) contribute to relapse by a self-seeding mechanism. This process requires the infiltration of PMN-MDSC and neutrophil extracellular traps (NET) formation. Genetic and pharmacological Enpp1 inhibition or NET blockade extend relapse-free survival. Furthermore, in combination with fractionated irradiation (FD), Enpp1 abrogation obliterates LRF. Mechanistically, Enpp1-generated adenosinergic metabolites enhance Haptoglobin (Hp) expression. This inflammatory mediator elicits myeloid invasiveness and promotes NET formation. Accordingly, a significant increase in ENPP1 and NET formation is detected in relapsed human breast cancer tumors. Moreover, high ENPP1 or HP levels are associated with poor prognosis. These findings unveil the ENPP1/HP axis as an unanticipated mechanism exploited by tumor cells linking inflammation to immune remodeling favoring local relapse.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{soree_life_2022,
title = {Life history of oysters influences Vibrio parahaemolyticus accumulation in Pacific oysters (Crassostrea gigas )},
author = {Marion Sorée and François Delavat and Christophe Lambert and Solen Lozach and Mathias Papin and Bruno Petton and Delphine Passerini and Lionel Dégremont and Dominique Hervio Heath},
url = {https://onlinelibrary.wiley.com/doi/10.1111/1462-2920.15996
hal-04202208v1 },
doi = {10.1111/1462-2920.15996},
issn = {1462-2912, 1462-2920},
year  = {2022},
date = {2022-05-01},
urldate = {2022-05-01},
journal = {Environmental Microbiology},
pages = {1462--2920.15996},
abstract = {Vibrio parahaemolyticus infection in humans is asso- ciated with raw oyster consumption. Evaluation of V. parahaemolyticus presence in oysters is of most interest because of the economic and public health issues that it represents. To explore V. para- haemolyticus accumulation and depuration in adult Crassostrea gigas, we developed a GFP-tagged V. parahaemolyticus strain (IFVp201-gfp+), as well as a rapid and efficient quantification method in C. gigas oysters haemolymph by flow cytometry. Impact of the life history of C. gigas on accumulation and depuration of V. parahaemolyticus IFVp201 was sub- sequently investigated. We found that naive oysters, i.e. grown in controlled facilities with UV treated sea- water, accumulated significantly more IFVp201 than environmental oysters, i.e. grown in intertidal envi- ronment. We hypothesized that environmental oys- ters could have been immune primed, thus could limit V. parahaemolyticus accumulation. Meanwhile, both naive and environmental oysters had similardepuration rates.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{nokey,
title = {An Efficient Chromatin Immunoprecipitation Protocol for the Analysis of Histone Modification Distributions in the Brown Alga Ectocarpus},
author = {Simon Bourdareau and Olivier Godfroy and Josselin Gueno and Delphine Scornet and Susana M. Coelho and Leila Tirichine and Jean Mark Cock},
url = {hal-03658367v1 },
doi = {doi: 10.3390/mps5030036},
year  = {2022},
date = {2022-04-25},
urldate = {2022-04-25},
journal = {Methods Protoc. },
volume = {36},
issue = {3},
pages = {36},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{pmid35179234,
title = {Technical note: Proton beam dosimetry at ultra-high dose rates (FLASH): Evaluation of GAFchromic™ (EBT3, EBT-XD) and OrthoChromic (OC-1) film performances},
author = {Daphnée Villoing and Charbel Koumeir and Arthur Bongrand and Arnaud Guertin and Ferid Haddad and Vincent Métivier and Freddy Poirier and Vincent Potiron and Noël Servagent and Stéphane Supiot and Grégory Delpon and Sophie Chiavassa},
url = {hal-03609664v1 },
doi = {10.1002/mp.15526},
issn = {2473-4209},
year  = {2022},
date = {2022-04-01},
urldate = {2022-04-01},
journal = {Med Phys},
volume = {49},
number = {4},
pages = {2732--2745},
abstract = {PURPOSE: The ARRONAX cyclotron facility offers the possibility to deliver proton beams from low to ultra-high dose rates (UHDR). As a good control of the dosimetry is a prerequisite of UHDR experimentations, we evaluated in different conditions the usability and the dose rate dependency of several radiochromic films commonly used for dosimetry in radiotherapy.

METHODS: We compared the dose rate dependency of three types of radiochromic films: GAFchromic™ EBT3 and GAFchromic™ EBT-XD (Ashland Inc., Wayne, NJ, USA), and OrthoChromic OC-1 (OrthoChrome Inc., Hillsborough, NJ, USA), after proton irradiations at various mean dose rates (0.25, 40, 1500, and 7500 Gy/s) and for 10 doses (2-130 Gy). We also evaluated the dose rate dependency of each film considering beam structures, from single pulse to multiple pulses with various frequencies.

RESULTS: EBT3 and EBT-XD films showed differences of response between conventional (0.25 Gy/s) and UHDR (7500 Gy/s) conditions, above 10 Gy. On the contrary, OC-1 films did not present overall difference of response for doses except below 3 Gy. We observed an increase of the netOD with the mean dose rate for EBT3 and EBT-XD films. OC-1 films did not show any impact of the mean dose rate up to 7500 Gy/s, above 3 Gy. No difference was found based on the beam structure, for all three types of films.

CONCLUSIONS: EBT3 and EBT-XD radiochromic films should be used with caution for the dosimetry of UHDR proton beams over 10 Gy. Their overresponse, which increases with mean dose rate and dose, could lead to non-negligible overestimations of the absolute dose. OC-1 films are dose rate independent up to 7500 Gy/s in proton beams. Films response is not impacted by the beam structure. A broader investigation of the usability of OC-1 films in UHDR conditions should be conducted at intermediate and higher mean dose rates and other beam energies.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{cancers14071765,
title = {Inhibiting Endothelin Receptors with Macitentan Strengthens the Bone Protective Action of RANKL Inhibition and Reduces Metastatic Dissemination in Osteosarcoma},
author = {Javier Muñoz-Garcia and Jorge William Vargas-Franco and Bénédicte Brounais-Le Royer and Denis Cochonneau and Jérôme Amiaud and Marie-Françoise Heymann and Dominique Heymann and Frédéric Lézot},
url = {https://www.mdpi.com/2072-6694/14/7/1765
inserm-03625367v1 },
doi = {10.3390/cancers14071765},
issn = {2072-6694},
year  = {2022},
date = {2022-03-30},
urldate = {2022-03-30},
journal = {Cancers},
volume = {14},
number = {7},
pages = {1765},
abstract = {Current treatments for osteosarcoma, combining conventional polychemotherapy and surgery, make it possible to attain a five-year survival rate of 70% in affected individuals. The presence of chemoresistance and metastases significantly shorten the patient&rsquo;s lifespan, making identification of new therapeutic tools essential. Inhibiting bone resorption has been shown to be an efficient adjuvant strategy impacting the metastatic dissemination of osteosarcoma, tumor growth, and associated bone destruction. Unfortunately, over-apposition of mineralized matrix by normal and tumoral osteoblasts was associated with this inhibition. Endothelin signaling is implicated in the functional differentiation of osteoblasts, raising the question of the potential value of inhibiting it alone, or in combination with bone resorption repression. Using mouse models of osteosarcoma, the impact of macitentan, an endothelin receptor inhibitor, was evaluated regarding tumor growth, metastatic dissemination, matrix over-apposition secondary to RANKL blockade, and safety when combined with chemotherapy. The results showed that macitentan has no impact on tumor growth or sensitivity to ifosfamide, but significantly reduces tumoral osteoid tissue formation and the metastatic capacity of the osteosarcoma. To conclude, macitentan appears to be a promising therapeutic adjuvant for osteosarcoma alone or associated with bone resorption inhibitors.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{sanejouand_at_2022,
title = {At least three xenon binding sites in the glycine binding domain of the N-methyl D-aspartate receptor},
author = {Yves-Henri Sanejouand},
url = {http://arxiv.org/abs/2203.02219
 hal-03863820v1 },
doi = {https://doi.org/10.1016/j.abb.2022.109265},
year  = {2022},
date = {2022-03-01},
urldate = {2022-03-01},
journal = {Archives of biochemistry and biophysics},
volume = {724},
pages = {109265},
abstract = {Xenon can produce general anesthesia. Its main protein target is the N-methyl-D-aspartate receptor, a ionotropic channel playing a pivotal role in the function of the central nervous system. The molecular mechanisms allowing this noble gas to have such a speciﬁc eﬀect remain obscure, probably as a consequence of the lack of structural data at the atomic level of detail. Herein, as a result of ﬁve independent molecular dynamics simulations, three diﬀerent binding sites were found for xenon in the glycine binding domain of the Nmethyl-D-aspartate receptor. The absolute binding free energy of xenon in these sites ranges between -8 and -14 kJ·mole−1. However, it depends signiﬁcantly upon the protein conformer chosen for performing the calculation, suggesting that larger values could probably be obtained, if other conformers were considered. These three sites are next to each other, one of them being next to the glycine site. This could explain why the F758W and F758Y mutations can prevent competitive inhibition by xenon without affecting glycine binding.},
note = {arXiv: 2203.02219},
keywords = {Quantitative Biology - Biomolecules, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{pmid35253891,
title = {Chromatin landscape associated with sexual differentiation in a UV sex determination system},
author = {Josselin Gueno and Michael Borg and Simon Bourdareau and Guillaume Cossard and Olivier Godfroy and Agnieszka Lipinska and Leila Tirichine and J Mark Cock and Susana M Coelho},
doi = {doi: 10.1093/nar/gkac145},
issn = {1362-4962},
year  = {2022},
date = {2022-03-01},
urldate = {2022-03-01},
journal = {Nucleic Acids Res},
volume = {50},
issue = {6},
pages = {3307-3322},
abstract = {In many eukaryotes, such as dioicous mosses and many algae, sex is determined by UV sex chromosomes and is expressed during the haploid phase of the life cycle. In these species, the male and female developmental programs are initiated by the presence of the U- or V-specific regions of the sex chromosomes but, as in XY and ZW systems, sexual differentiation is largely driven by autosomal sex-biased gene expression. The mechanisms underlying the regulation of sex-biased expression of genes during sexual differentiation remain elusive. Here, we investigated the extent and nature of epigenomic changes associated with UV sexual differentiation in the brown alga Ectocarpus, a model UV system. Six histone modifications were quantified in near-isogenic lines, leading to the identification of 16 chromatin signatures across the genome. Chromatin signatures correlated with levels of gene expression and histone PTMs changes in males versus females occurred preferentially at genes involved in sex-specific pathways. Despite the absence of chromosome scale dosage compensation and the fact that UV sex chromosomes recombine across most of their length, the chromatin landscape of these chromosomes was remarkably different to that of autosomes. Hotspots of evolutionary young genes in the pseudoautosomal regions appear to drive the exceptional chromatin features of UV sex chromosomes.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{jubelin2022biological,
title = {Biological evidence of cancer stem-like cells and recurrent disease in osteosarcoma},
author = {Camille Jubelin and Javier Munoz-Garcia and Denis Cochonneau and Emilie Moranton and Marie Françoise Heymann and Dominique Heymann},
url = { inserm-03550410v1 },
doi = {10.20517/cdr.2021.130},
year  = {2022},
date = {2022-02-16},
urldate = {2022-02-16},
journal = {Cancer Drug Resistance},
volume = {5},
issue = {5},
pages = {184-198},
abstract = {Sarcomas are a large family of cancers originating in the mesenchyme. Composed of more than 100 histological subtypes, soft tissue and bone sarcomas remain clinically challenging, particularly in children and adolescents in whom sarcomas are the second most common malignant entities. Osteosarcoma is the main primary bone tumor in adolescents and young adults and is characterized by a high propensity to induce distant metastatic foci and become multi-drug resistant. The innate and acquired resistance of osteosarcoma can be explained by high histological heterogeneity and genetic/molecular diversity. In the last decade, the notion of cancer stem-like cells (CSCs) has emerged. This subset of cancer cells has been linked to drug resistance properties, recurrence of the disease, and therapeutic failure. Although CSCs remain controversial, many elements are in favor of them playing a role in the development of the drug resistance profile. The present review gives a brief overview of the most recent biological evidence of the presence of CSCs in osteosarcomas and their role in the drug resistance profile of these rare oncological entities. Their use as promising therapeutic targets is discussed.},
keywords = {team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{pmid35190870,
title = {FVIII regulates the molecular profile of endothelial cells: functional impact on the blood barrier and macrophage behavior},
author = {Marie Cadé and Javier Muñoz-Garcia and Antoine Babuty and Louis Paré and Denis Cochonneau and Karim Fekir and Mathias Chatelais and Marie-Françoise Heymann and Anna Lokajczyk and Catherine Boisson-Vidal and Dominique Heymann},
url = {hal-03600694v1 },
doi = {10.1007/s00018-022-04178-5},
issn = {1420-9071},
year  = {2022},
date = {2022-02-01},
urldate = {2022-02-01},
journal = {Cell Mol Life Sci},
volume = {79},
number = {3},
pages = {145},
abstract = {Hemophilia A is an inherited X-linked recessive bleeding disorder caused by deficient activity of blood coagulation factor VIII (FVIII). In addition, hemophilia patients show associated diseases including osteopenia, altered inflammation and vascular fragility which may represent the consequence of recurrent bleeding or may be related to the direct FVIII deficiency. Nowadays, recombinant FVIII is proposed to treat hemophilia patients with no circulating FVIII inhibitor. Initially described as a coenzyme to factor IXa for initiating thrombin generation, there is emerging evidence that FVIII is involved in multiple biological systems, including bone, vascular and immune systems. The present study investigated: (i) the functional activities of recombinant human FVIII (rFVIII) on endothelial cells, and (ii) the impact of rFVIII activities on the functional interactions of human monocytes and endothelial cells. We then investigated whether rFVIII had a direct effect on the adhesion of monocytes to the endothelium under physiological flow conditions. We observed that direct biological activities for rFVIII in endothelial cells were characterized by: (i) a decrease in endothelial cell adhesion to the underlying extracellular matrix; (ii) regulation of the transcriptomic and protein profiles of endothelial cells; (iii) an increase in the vascular tubes formed and vascular permeability in vitro; and (iv) an increase in monocyte adhesion activated endothelium and transendothelial migration. By regulating vascular permeability plus leukocyte adhesion and transendothelial migration, the present work highlights new biological functions for FVIII.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{dos2022neuroprotective,
title = {Neuroprotective effects of resveratrol in in vivo and in vitro experimental models of Parkinson’s disease: A systematic review},
author = {Michele Goulart Dos Santos and Lucia Emanueli Schimith and Corinne André-Miral and Ana Luiza Muccillo-Baisch and Bruno Dutra Arbo and Mariana Appel Hort},
editor = {Springer},
doi = {10.1007/s12640-021-00450-x},
year  = {2022},
date = {2022-01-12},
urldate = {2022-01-12},
journal = {Neurotoxicity Research},
pages = {1--27},
publisher = {Springer},
abstract = {Parkinson’s disease (PD) is currently the second most common neurodegenerative disease, being characterized by motor and non-motor symptoms. The therapeutic options available for its treatment are limited, do not slow the progression of the disease, and have serious side effects. For this reason, many studies have sought to find compounds with neuroprotective properties that bring additional benefits to current therapy. In this context, resveratrol is a phenolic compound, found in many plant species, capable of crossing the blood–brain barrier and having multiple biological properties. Experimental studies in vitro and in vivo have shown that it can prevent or slow the progression of a variety of diseases, including PD. In this systematic review, we summarize the effects of resveratrol in experimental in vivo and in vitro models of PD and discuss the molecular mechanisms involved in its action. The bibliographic search was performed in the databases of PubMed, Web of Science, SciELO, and Google Scholar, and based on the inclusion criteria, 41 articles were selected and discussed. Most of the included studies have demonstrated neuroprotective effects of resveratrol. In general, resveratrol prevented behavioral and/or neurological disorders, improved antioxidant defenses, reduced neuroinflammatory processes, and inhibited apoptosis. In summary, this systematic review offers important scientific evidence of neuroprotective effects of resveratrol in PD and also provide valuable information about its mechanism of action that can support future clinical studies.},
keywords = {Funregiox, team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{pmid35087753,
title = {Cost and Toxicity Comparisons of Two IMRT Techniques for Prostate Cancer: A Micro-Costing Study and Weighted Propensity Score Analysis Based on a Prospective Study},
author = {Ingrid Masson and Martine Bellanger and Geneviève Perrocheau and Marc-André Mahé and David Azria and Pascal Pommier and Nathalie Mesgouez-Nebout and Philippe Giraud and Didier Peiffert and Bruno Chauvet and Philippe Dudouet and Naji Salem and Georges Noël and Jonathan Khalifa and Igor Latorzeff and Catherine Guérin-Charbonnel and Stéphane Supiot},
doi = {10.3389/fonc.2021.781121},
issn = {2234-943X},
year  = {2022},
date = {2022-01-11},
urldate = {2021-01-01},
journal = {Front Oncol},
volume = {11},
pages = {781121},
abstract = {Background: Intensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) has become the standard treatment for patients with high-risk prostate cancer. Two techniques of rotational IMRT are commonly used in this indication: Volumetric Modulated Arc Therapy (VMAT) and helical tomotherapy (HT). To the best of our knowledge, no study has compared their related costs and clinical effectiveness and/or toxicity in prostate cancer. We aimed to assess differences in costs and toxicity between VMAT and HT in patients with high-risk prostate cancer with pelvic irradiation.

Material and Methods: We used data from the "RCMI pelvis" prospective multicenter study (NCT01325961) including 155 patients. We used a micro-costing methodology to identify cost differences between VMAT and HT. To assess the effects of the two techniques on total actual costs per patient and on toxicity we used stabilized inverse probability of treatment weighting.

Results: The mean total cost for HT, €2019 3,069 (95% CI, 2,885-3,285) was significantly higher than the mean cost for VMAT €2019 2,544 (95% CI, 2,443-2,651) (p &lt;.0001). The mean ± SD labor and accelerator cost for HT was €2880 (± 583) and €1978 (± 475) for VMAT, with 81 and 76% for accelerator, respectively. Acute GI and GU toxicity were more frequent in VMAT than in HT (p = .021 and p = .042, respectively). Late toxicity no longer differed between the two groups up to 24 months after completion of treatment.

Conclusion: Use of VMAT was associated with lower costs for IMRT planning and treatment than HT. Similar stabilized long-term toxicity was reported in both groups after higher acute GI and GU toxicity in VMAT. The estimates provided can benefit future modeling work like cost-effectiveness analysis.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@patent{colliec2022anti,
title = {Anti-metastatic marine bacterial exopolysaccharide derivative and uses thereof},
author = {Sylvia Colliec-Jouault and Corinne Sinquin and Jacqueline Ratiskol and Dominique Heymann and Carmen Ruiz-Velasco and Julie Chesneau},
url = {https://patents.google.com/patent/US11219638B2/en},
year  = {2022},
date = {2022-01-11},
urldate = {2022-01-11},
publisher = {Google Patents},
abstract = {The invention provides a low-molecular-weight (15 kDa) over-sulfated exopolysaccharide (GYS15) prepared from a marine native exopolysaccharide excreted by a mesophilic marine bacterium from a deep-sea hydrothermal environment, and relates to the use of this low-molecular-weight over-sulfated exopolysaccharide for the prevention or inhibition of metastases formation.},
note = {US Patent 11,219,638},
keywords = {team 3},
pubstate = {published},
tppubtype = {patent}
}
@article{pmid35070993,
title = {Mapping of Recurrence Sites Following Adjuvant or Salvage Radiotherapy for Prostate Cancer Patients},
author = {Ana Gonzalez-Moya and Stéphane Supiot and Valérie Seegers and Thibaut Lizée and Florence Legouté and Tanguy Perennec and Gilles Calais},
doi = {10.3389/fonc.2021.787347},
issn = {2234-943X},
year  = {2022},
date = {2022-01-05},
urldate = {2021-01-01},
journal = {Front Oncol},
volume = {11},
pages = {787347},
abstract = {Introduction: Although salvage and adjuvant radiotherapy (RT) are effective in prostate cancer (PC) patients, 30%-40% of men will have disease progression. The objective was to describe the pattern of recurrence in PC patients with biochemical failure (BF) following postoperative RT.

Methods: We retrospectively analyzed 935 PC patients treated from 2009 to 2019 with adjuvant or salvage RT at the Institut de Cancérologie de l&#039;Ouest. Of these, 205 (22%) developed BF of whom 166 underwent imaging. Patients with identified radiologic failure prior any specific treatment were included to determine the site of relapse categorized as local (L)-only, locoregional (LR), or metastatic (M) recurrence. Main disease characteristics and RT fields were examined in relation to sites of recurrence.

Results: One hundred forty-one patients were identified with 244 sites of failure on imaging. Of these, 108 patients had received RT to the PB alone and 33 RT to the PB and pelvic lymph nodes (PB+PLN). Androgen-deprivation therapy was used concomitantly in 50 patients (35%). The median PSA at imaging was 1.6 ng/ml (range, 0-86.7). In all, 74 patients (52%) had M disease (44% in the PB group and 79% in the PB+PLN group), 61 (43%) had LR failure (52% in the PB alone group and 15% in the PB+PLN group), and six (4%) had L-only failure, at a median of 26.7 months (range, 5-110.3) from RT. Metastases were in extra-pelvic LN (37 (15%)), bones (66 (27%)), and visceral organs (eight (3%)). Fifty-three (48%) of the pelvic LN failures in the PB group would have been encompassed by standard PLN RT volume.

Conclusion: We found that most patients evaluated for BF after postoperative RT recurred outside the RT field. Isolated pelvic nodal failure was rare in those receiving RT to the PB+PLN but accounted for half of failures in those receiving PB alone RT. Imaging directed salvage treatment could be helpful to personalize radiation therapy plan.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@inbook{MUNOZGARCIA202227,
title = {Chapter 3 - Mammalian models of bone sarcomas},
author = {Javier Muñoz-Garcia and Frédéric Lézot and Denis Cochonneau and Agamemnon E. Grigoriadis and Dominique Heymann},
editor = {Dominique Heymann},
url = {https://www.sciencedirect.com/science/article/pii/B978012821666800013X},
doi = {https://doi.org/10.1016/B978-0-12-821666-8.00013-X},
isbn = {978-0-12-821666-8},
year  = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
booktitle = {Bone Sarcomas and Bone Metastases - From Bench to Bedside (Third Edition)},
pages = {27-34},
publisher = {Academic Press},
edition = {Third Edition},
series = {Bone Sarcomas and Bone Metastases - From Bench to Bedside (Third Edition)},
abstract = {In oncology, animal models represent key tools to decipher molecular mechanisms driven tumor growth and disease progression, to study the contribution of the tumor microenvironment in these processes, and to identify new biomarkers and new therapeutic targets. Bone sarcomas are rare primary bone malignancies characterized by a high propensity to form lung metastases and/or by a high rate of local recurrence according to the histological subtype. To better delineate the pathogenesis of primary bone cancers and to develop new therapies, many preclinical models have been set up in mouse, rat, pig, and dog mimicking the human pathology. These models include tumors induced by inoculation of cancer cells in immune-competent or immune-deficient animals and tumors forming in genetically engineered animal models. The present chapter will give a brief overview of the main animal models currently available for studying the biology of bone sarcomas including their advantages and drawbacks.},
keywords = {Chondrosarcoma, Ewing&#039;s sarcoma, Osteosarcoma},
pubstate = {forthcoming},
tppubtype = {inbook}
}
@article{rabe2022cellular,
title = {Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide Treatment},
author = {Marion Rabé and Lucie Fonteneau and Lisa Oliver and Alvaro Morales-Molina and Camille Jubelin and Javier Garcia-Castro and Dominique Heymann and Catherine Gratas and François M Vallette},
year  = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Frontiers in Cell and Developmental Biology},
volume = {10},
pages = {975},
publisher = {Frontiers},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid36340383,
title = {Wild  species: A reservoir of resistance genes for sustainable pyramidal resistance to broomrape in sunflower},
author = {Mireille Chabaud and Marie-Christine Auriac and Marie-Claude Boniface and Sabine Delgrange and Tifaine Folletti and Marie-Françoise Jardinaud and Alexandra Legendre and Begoña Pérez-Vich and Jean-Bernard Pouvreau and Leonardo Velasco and Philippe Delavault and Stéphane Muños},
url = {hal-03877893v1 },
doi = {10.3389/fpls.2022.1038684},
issn = {1664-462X},
year  = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Front Plant Sci},
volume = {13},
pages = {1038684},
abstract = { Wall., sunflower broomrape, is one of the major pests for the sunflower crop. Breeding for resistant varieties in sunflower has been the most efficient method to control this parasitic weed. However, more virulent broomrape populations continuously emerge by overcoming genetic resistance. It is thus essential to identify new broomrape resistances acting at various stages of the interaction and combine them to improve resistance durability. In this study, 71 wild sunflowers and wild relatives accessions from 16  species were screened in pots for their resistance to broomrape at the late emergence stage. From this initial screen, 18 accessions from 9 species showing resistance, were phenotyped at early stages of the interaction: the induction of broomrape seed germination by sunflower root exudates, the attachment to the host root and the development of tubercles in rhizotron assays. We showed that wild  accessions are an important source of resistance to the most virulent broomrape races, affecting various stages of the interaction: the inability to induce broomrape seed germination, the development of incompatible attachments or necrotic tubercles, and the arrest of emerged structure growth. Cytological studies of incompatible attachments showed that several cellular mechanisms were shared among resistant  species.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{nokey,
title = {Characterization of Redox Sensitive Brown Algal Mannitol-1-Phosphatases},
author = {Yoran Le Strat and Thierry Tonon and Catherine Leblanc and Agnès Groisillier},
url = {https://doi.org/10.3390/phycology3010001
https://hal.science/hal-04256946v1
 hal-04256946v1},
doi = {10.3390/phycology3010001},
year  = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
abstract = {Citation: Le Strat, Y.; Tonon, T.; Leblanc, C.; Groisillier, A. Characterization of Redox Sensitive Brown Algal Mannitol-1-Phosphatases. Phycology 2023, 3, 1-12. https:// Abstract: Macroalgae (seaweeds) are key primary producers in marine coastal habitats and largely contribute to global ocean carbon fluxes. They also represent attractive renewable feedstock for the production of biofuels, food, feed, and bioactive. Brown algae are seaweeds that produce alginates and fucose containing sulfated polysaccharides in their cell wall and laminarin and mannitol for carbon storage. The availability of genomes of the kelp Saccharina japonica and of the filamentous Ectocarpus sp. paved the way for the biochemical characterization of recombinant enzymes involved in their polysaccharide and carbohydrates synthesis, including, notably, mannitol. Brown algal mannitol biosynthesis starts with the conversion of fructose-6-phospate into mannitol-1-phosphate (mannitol-1P), and this intermediate is hydrolysed by a haloacid dehalogenase phosphatase (M1Pase) to produce mannitol. We report here the biochemical characterization of a second M1Pase in Ectocarpus sp. (EsM1Pase1). Both Ectocarpus M1Pases were redox-sensitive enzymes, with EsM1Pase1 active only in presence of the reducing agent. Such catalytic properties have not been observed for any M1Pases yet. EsM1Pases were specific to mannitol-1-P, in contrast to S. japonica M1Pases that could act on other phosphorylated sugars. Finally, brown algal M1Pases formed two well-supported clades, with possible distinct subcellular localization and physiological role(s) under diverse environmental conditions and/or life cycle stages.},
keywords = {brown algae, Ectocarpus sp, mannitol cycle, mannitol-1-phosphatase, recombinant protein, redox sensitivity, us2b},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34311113,
title = {FVIII at the crossroad of coagulation, bone and immune biology: Emerging evidence of biological activities beyond hemostasis},
author = {Marie Cadé and Javier Muñoz-Garcia and Antoine Babuty and Marc Fouassier and Marie-Francoise Heymann and Paul E Monahan and Dominique Heymann},
doi = {10.1016/j.drudis.2021.07.015},
issn = {1878-5832},
year  = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Drug Discov Today},
volume = {27},
number = {1},
pages = {102--116},
abstract = {Hemophilia A is an X-linked hereditary disorder that results from deficient coagulation factor VIII (FVIII) activity, leading to spontaneous bleeding episodes, particularly in joints and muscles. FVIII deficiency has been associated with altered bone remodeling, dysregulated macrophage polarization, and inflammatory processes that are associated with the neoformation of abnormal blood vessels. Treatment based on FVIII replacement can lead to the development of inhibitors that render FVIII concentrate infusion ineffective. In this context, hemophilia has entered a new therapeutic era with the development of new drugs, such as emicizumab, that seek to restore the hemostatic balance by bypassing pathologically acquired antibodies. We discuss the potential extrahemostatic functions of FVIII that may be crucial for defining future therapies in hemophilia.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34816023,
title = {Cytokine release syndrome and tumor lysis syndrome in a multiple myeloma patient treated with palliative radiotherapy: A case report and review of the literature},
author = {Axel Cailleteau and Cyrille Touzeau and Bastien Jamet and Valentine Guimas and Emmanuel Jouglar and Stéphane Supiot},
doi = {10.1016/j.ctro.2021.11.004},
issn = {2405-6308},
year  = {2022},
date = {2022-01-01},
urldate = {2021-11-12},
journal = {Clin Transl Radiat Oncol},
volume = {32},
pages = {24--28},
abstract = {We present the case of a 53-year-old woman treated with analgesic radiotherapy for a multiple myeloma bone lesion of the forearm. After a first fraction of 5 Gray (Gy), she presented with an acute respiratory syndrome with fever a few hours after the treatment. The same symptoms occurred after the second fraction 3 days later. The patient recovered quickly thanks to intravenous hydration and suspension of the radiotherapy. Biological tests revealed a tumor lysis syndrome. We concluded that the clinical symptoms could be defined as cytokine release syndrome. This is the second time in the literature that cytokine release syndrome has been described following radiotherapy. First, we synthesize TLS and radiotherapy to determine how radiotherapy could be a trigger associated with other well-known factors. Furthermore, we discuss radiotherapy and cytokine release syndrome.

Summary: We present the case of a woman treated with analgesic radiotherapy for a multiple myeloma bone lesion. Following the first and the second treatment fraction, the patient presented with an acute respiratory syndrome with fever and biological tests revealed a tumor lysis syndrome. We concluded that the clinical symptoms could be defined as cytokine release syndrome. Furthermore, we discuss how radiotherapy could be a trigger of cytokine release syndrome and tumor lysis syndrome in association with chemotherapy drugs.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34969622,
title = {Guide for paediatric radiotherapy procedures},
author = {A Laprie and V Bernier and L Padovani and V Martin and C Chargari and S Supiot and L Claude},
doi = {10.1016/j.canrad.2021.11.018},
issn = {1769-6658},
year  = {2021},
date = {2021-12-27},
urldate = {2021-12-27},
journal = {Cancer Radiother},
abstract = {A third of children with cancer receive radiotherapy as part of their initial treatment, which represents 800 paediatric irradiations per year in France carried out in 15 specialized centres approved on the recommendations of the French national cancer institute in decreasing order of frequency, the types of cancer that require irradiation are: brain tumours, neuroblastomas, Ewing's sarcomas, Hodgkin's lymphomas, soft tissue sarcomas including rhabdomyosarcomas, and nephroblastomas. The treatment guidelines follow the recommendations of the French society for childhood cancers (SFCE) or the French and European prospective protocols. The therapeutic indications, the technical and/and ballistic choices of complex cases are frequently discussed during bimonthly paediatric radiotherapy technical web-conferences. All cancers combined, overall survival being 80%, long-term toxicity logically becomes an important concern, making the preparation of treatments complex. The irradiation methods include all the techniques currently available: 3D conformational irradiation, intensity modulation radiation therapy, irradiation under normal or hypofractionated stereotaxic conditions, brachytherapy and proton therapy. We present the update of the recommendations of the French society for radiation oncology on the indications, the technical methods of realization and the organisation and the specificities of paediatric radiation oncology.},
keywords = {out_lab},
pubstate = {forthcoming},
tppubtype = {article}
}
@article{pmid35004302,
title = {Drug Intensification in Future Postoperative Radiotherapy Practice in Biochemically-Relapsing Prostate Cancer Patients},
author = {Axel Cailleteau and Paul Sargos and Fred Saad and Igor Latorzeff and Stéphane Supiot},
doi = {10.3389/fonc.2021.780507},
issn = {2234-943X},
year  = {2021},
date = {2021-12-24},
urldate = {2021-01-01},
journal = {Front Oncol},
volume = {11},
pages = {780507},
abstract = {Although salvage prostate bed radiotherapy is highly effective in biochemically-relapsing prostate cancer patients following prostatectomy, relapses remain frequent and improvements are needed. Randomized phase 3 trials have shown the benefit of adding androgen-depriving therapy to irradiation, but not all patients benefit from this combination. Preclinical studies have shown that novel agents targeting the androgen receptor, DNA repair, PI3K/AKT/mTOR pathways, or the hypoxic microenvironment may help increase the response to prostate bed irradiation while minimizing potential side effects. This perspective review focuses on the most relevant molecules that may have an impact when combined with salvage radiotherapy, and underlines the strategies that need to be developed to increase the efficacy of salvage post-prostatectomy radiotherapy in prostate cancer patients.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34955419,
title = {External radiotherapy for prostatic cancers},
author = {R de Crevoisier and S Supiot and G Créhange and P Pommier and I Latorzeff and O Chapet and D Pasquier and P Blanchard and U Schick and V Marchesi and P Sargos and C Hennequin},
doi = {10.1016/j.canrad.2021.11.017},
issn = {1769-6658},
year  = {2021},
date = {2021-12-20},
urldate = {2021-12-20},
journal = {Cancer Radiother},
abstract = {We present the update of the recommendations of the French society of oncological radiotherapy on external radiotherapy of prostate cancer. External radiotherapy is intended for all localized prostate cancers, and more recently for oligometastatic prostate cancers. The irradiation techniques are detailed. Intensity-modulated radiotherapy combined with prostate image-guided radiotherapy is the recommended technique. A total dose of 74 to 80Gy is recommended in case of standard fractionation (2Gy per fraction). Moderate hypofractionation (total dose of 60Gy at a rate of 3Gy per fraction over 4 weeks) in the prostate has become a standard of therapy. Simultaneous integrated boost techniques can be used to treat lymph node areas. Extreme hypofractionation (35 to 40Gy in five fractions) using stereotactic body radiotherapy can be considered a therapeutic option to treat exclusively the prostate. The postoperative irradiation technique, indicated mainly in case of biological recurrence and lymph node involvement, is detailed.},
keywords = {out_lab},
pubstate = {forthcoming},
tppubtype = {article}
}
@article{pmid34953712,
title = {Specificities of clinical research in radiotherapy},
author = {C Hennequin and D Azria and P Blanchard and G Créhange and É Deutsch and A Lisbona and É Moyal and D Pasquier and L Roca and S Supiot and P Giraud},
doi = {10.1016/j.canrad.2021.11.011},
issn = {1769-6658},
year  = {2021},
date = {2021-12-16},
urldate = {2021-12-16},
journal = {Cancer Radiother},
abstract = {The aim of this review is to present the specificities of clinical research in radiation oncology. Objectives are similar to all research in oncology: to improve the efficacy and to decrease toxic effects. Phase III trials remain the main methodology to demonstrate an improvement in efficiency, but phase I-II and registers are also important tools to validate an improvement in the therapeutic index with new technologies. In this article we discuss the special features of end-points, selection of population, and design for radiation oncology clinical trials. Quality control of delivered treatments is an important component of these protocols. Financial issues are also discussed, in the particular context of France.},
keywords = {out_lab},
pubstate = {forthcoming},
tppubtype = {article}
}
@article{pmid34976358,
title = {Luminol anchors improve the electrochemical-tyrosine-click labelling of proteins},
author = {Sébastien Depienne and Dimitri Alvarez-Dorta and Mikael Croyal and Ranil C T Temgoua and Cathy Charlier and David Deniaud and Mathieu Mével and Mohammed Boujtita and Sébastien G Gouin},
url = {hal-03429234v2 },
doi = {10.1039/d1sc04809k},
issn = {2041-6520},
year  = {2021},
date = {2021-12-01},
urldate = {2021-12-01},
journal = {Chem Sci},
volume = {12},
number = {46},
pages = {15374--15381},
abstract = {New methods for chemo-selective modifications of peptides and native proteins are important in chemical biology and for the development of therapeutic conjugates. Less abundant and uncharged amino-acid residues are interesting targets to form less heterogeneous conjugates and preserve biological functions. Phenylurazole (PhUr), -methylphenylurazole (NMePhUr) and -methylluminol (NMeLum) derivatives were described as tyrosine (Y) anchors after chemical or enzymatic oxidations. Recently, we developed the first electrochemical Y-bioconjugation method coined eY-click to activate PhUr in biocompatible media. In this work, we assessed the limitations, benefits and relative efficiencies of eY-click conjugations performed with a set of PhUr, NMePhUr and NMeLum derivatives. Results evidenced a high efficiency of NMeLum that showed a complete Y-chemoselectivity on polypeptides and biologically relevant proteins after soft electrochemical activation. Side reactions on nucleophilic or heteroaromatic amino-acids such as lysine or tryptophan were never observed during mass spectrometry analysis. Myoglobine, bovine serum albumin, a plant mannosidase, glucose oxidase and the therapeutically relevant antibody trastuzumab were efficiently labelled with a fluorescent probe in a two-step approach combining eY-click and strain-promoted azide-alkyne cyclization (SPAAC). The proteins conserved their structural integrity as observed by circular dichroism and the trastuzumab conjugate showed a similar binding affinity for the natural HER2 ligand as shown by bio-layer interferometry. Compared to our previously described protocol with PhUr, eY-click with NMeLum species showed faster reaction kinetics, higher (complete) Y-chemoselectivity and reactivity, and offers the interesting possibility of the double tagging of solvent-exposed Y.},
keywords = {impact},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34498760,
title = {Strigolactones (SLs) modulate the plastochron by regulating KLUH (KLU) transcript abundance in Arabidopsis},
author = {Florent Cornet and Jean-Paul Pillot and Philippe Le Bris and Jean-Bernard Pouvreau and Nicolas Arnaud and Alexandre de Saint Germain and Catherine Rameau},
doi = {10.1111/nph.17725},
issn = {1469-8137},
year  = {2021},
date = {2021-12-01},
urldate = {2021-12-01},
journal = {New Phytol},
volume = {232},
number = {5},
pages = {1909--1916},
abstract = {The timing of leaf emergence at the shoot apical meristem, or plastochron, is highly regulated in plants. Among the genes known to regulate the plastochron in Arabidopsis (Arabidopsis thaliana), KLUH (KLU), orthologous to the rice (Oryza sativa) PLASTOCHRON1, encodes the cytochrome P450 CYP78A5, and is thought to act through generation of a still unknown mobile signal. As klu mutants display not only a short plastochron but also a branching phenotype reminiscent of strigolactone (SL) mutants, we investigated whether KLU/CYP78A5 is involved in SL biosynthesis. We combined a genetic approach, a parasitic plant seed germination bioassay to test klu root exudates, and analysis of transcript abundances of SL-biosynthesis genes in the Arabidopsis klu mutants. We demonstrate that KLU is not involved in the SL-biosynthesis pathway. Moreover, this work allowed us to uncover a new role for SL during Arabidopsis development in modulating plastochron via a KLU-dependent pathway. Globally our data reveal that KLU is required for plastochron-specific SL responses, a first indication of crosstalk between SL and the KLU-derived signal.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@conference{nokey,
title = {Proton beam FLASH online monitoring at ARRONAX cyclotron},
author = { Noël Servagent, Charbel Koumeir, Guillaume Blain, A. Bongrand, Sophie Chiavassa, Sylvain Deffe, Grégory Delpon, Arnaud Guertin, Stéphane Lucas, Vincent Métivier, Quentin Mouchard, Freddy Poirier, Vincent Potiron, Lucas Schoenauen, Edmond Sterpin, Daphnée Villoing, Rudi Labarbe, Severine Rossomme, Ferid Haddad },
url = { hal-03934393v1 },
year  = {2021},
date = {2021-12-01},
urldate = {2021-12-01},
keywords = {team 3},
pubstate = {published},
tppubtype = {conference}
}
@conference{nokey,
title = {UHDR proton beam vs conventional: hydrogen peroxide as FLASH effect sensor},
url = {hal-03957666v1 },
year  = {2021},
date = {2021-12-01},
urldate = {2021-12-01},
keywords = {team 3},
pubstate = {published},
tppubtype = {conference}
}
@article{Bourdareau2021,
title = {Histone modifications during the life cycle of the brown alga Ectocarpus},
author = {Simon Bourdareau and Leila Tirichine and Bérangère Lombard and Damarys Loew and Delphine Scornet and Yue Wu and Susana M Coelho and Mark J Cock},
url = {https://pubmed.ncbi.nlm.nih.gov/33397407/},
doi = {10.1186/s13059-020-02216-8},
issn = {1474760X},
year  = {2021},
date = {2021-12-01},
journal = {Genome Biology},
volume = {22},
number = {1},
publisher = {BioMed Central Ltd},
abstract = {Background: Brown algae evolved complex multicellularity independently of the animal and land plant lineages and are the third most developmentally complex phylogenetic group on the planet. An understanding of developmental processes in this group is expected to provide important insights into the evolutionary events necessary for the emergence of complex multicellularity. Here, we focus on mechanisms of epigenetic regulation involving post-translational modifications of histone proteins. Results: A total of 47 histone post-translational modifications are identified, including a novel mark H2AZR38me1, but Ectocarpus lacks both H3K27me3 and the major polycomb complexes. ChIP-seq identifies modifications associated with transcription start sites and gene bodies of active genes and with transposons. H3K79me2 exhibits an unusual pattern, often marking large genomic regions spanning several genes. Transcription start sites of closely spaced, divergently transcribed gene pairs share a common nucleosome-depleted region and exhibit shared histone modification peaks. Overall, patterns of histone modifications are stable through the life cycle. Analysis of histone modifications at generation-biased genes identifies a correlation between the presence of specific chromatin marks and the level of gene expression. Conclusions: The overview of histone post-translational modifications in the brown alga presented here will provide a foundation for future studies aimed at understanding the role of chromatin modifications in the regulation of brown algal genomes.},
keywords = {brown algae, ChIP-seq, Chromatin, Ectocarpus, Gametophyte, Histone modification, Life cycle, Multicellularity, Polycomb complex, Sporophyte, team 5, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34955420,
title = {Radiotherapy of bone metastases},
author = {S Thureau and S Supiot and E Jouglar and M Rogé and L Lebret and A Hadj Henni and G Beldjoudi and J-L Lagrange and J-C Faivre},
doi = {10.1016/j.canrad.2021.11.021},
issn = {1769-6658},
year  = {2021},
date = {2021-12-01},
urldate = {2021-12-01},
journal = {Cancer Radiother},
abstract = {We present the update of the recommendations of the French society of oncological radiotherapy on bone metastases. This is a common treatment in the management of patients with cancer. It is a relatively simple treatment with proven efficacy in reducing pain or managing spinal cord compression. More complex treatments by stereotaxis can be proposed for oligometastatic patients or in case of reirradiation. In this context, increased vigilance should be given to the risks to the spinal cord.},
keywords = {out_lab},
pubstate = {forthcoming},
tppubtype = {article}
}
@article{pmid34885179,
title = {Oncologic Impact and Safety of Pre-Operative Radiotherapy in Localized Prostate and Bladder Cancer: A Comprehensive Review from the Cancerology Committee of the Association Française d'Urologie},
author = {Paul Sargos and Stéphane Supiot and Gilles Créhange and Gaëlle Fromont-Hankard and Eric Barret and Jean-Baptiste Beauval and Laurent Brureau and Charles Dariane and Gaëlle Fiard and Mathieu Gauthé and Romain Mathieu and Guilhem Roubaud and Alain Ruffion and Raphaële Renard-Penna and Yann Neuzillet and Morgan Rouprêt and Guillaume Ploussard},
editor = {MDPI},
doi = {10.3390/cancers13236070},
issn = {2072-6694},
year  = {2021},
date = {2021-12-01},
urldate = {2021-12-01},
journal = {Cancers (Basel)},
volume = {13},
number = {23},
abstract = {Preoperative radiotherapy (RT) is commonly used for the treatment of various malignancies, including sarcomas, rectal, and gynaecological cancers, but it is preferentially used as a competitive treatment to radical surgery in uro-oncology or as a salvage procedure in cases of local recurrence. Nevertheless, preoperative RT represents an attractive strategy to prevent from intraoperative tumor seeding in the operative field, to sterilize microscopic extension outside the organ, and to enhance the pathological and/or imaging tumor response rate. Several clinical works support this research field in uro-oncology. In this review article, we summarized the oncologic impact and safety of preoperative RT in localized prostate and muscle-invasive bladder cancer. Preliminary studies suggest that both modalities can be complementary as initial primary tumor treatments and that a pre-operative radiotherapy strategy could be beneficial in a well-defined population of patients who are at a very high-risk of local relapse. Future prospective trials are warranted to evaluate the oncologic benefit of such a combination of local treatments in addition to new life-prolonging systemic therapies, such as immunotherapy, and new generation hormone therapies. Moreover, the safety and the feasibility of salvage surgical procedures due to non-response or local recurrence after pelvic RT remain poorly evaluated in that context.},
keywords = {out_lab, radiotherapy},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34881187,
title = {Post-Operative Radiotherapy in Prostate Cancer: Is It Time for a Belt and Braces Approach?},
author = {Nicolas Giraud and Nicolas Benziane-Ouaritini and Ulrike Schick and Jean-Baptiste Beauval and Ahmad Chaddad and Tamim Niazi and Mame Daro Faye and Stéphane Supiot and Paul Sargos and Igor Latorzeff},
doi = {10.3389/fonc.2021.781040},
issn = {2234-943X},
year  = {2021},
date = {2021-11-18},
urldate = {2021-11-18},
journal = {Front Oncol},
volume = {11},
pages = {781040},
abstract = {Approximately 30% of patients treated with radical prostatectomy (RP) for prostate cancers experience biochemical recurrence (BCR). Post-operative radiation therapy (RT) can be either offered immediately after the surgery in case of aggressive pathological features or proposed early if BCR occurs. Until recently, little data were available regarding the optimal RT timing, protocol, volumes to treat, and the benefit of adding androgen deprivation therapies to post-operative RT. In this review, we aim to pragmatically discuss current literature data on these points. Early salvage RT appears to be the optimal post-operative approach, improving oncological outcomes especially with low prostate-specific antigen (PSA) levels, as well as sparing several unnecessary adjuvant treatments. The standard RT dose is still 64-66 Gy to the prostate bed in conventional fractionation, but hypofractionation protocols are emerging pending on late toxicity data. Several scientific societies have published contouring atlases, even though they are heterogeneous and deserve future consensus. During salvage RT, the inclusion of pelvic lymph nodes is also controversial, but preliminary data show a possible benefit for PSA &gt; 0.34 ng/ml at the cost of increased hematological side effects. Concomitant ADT and its duration are also discussed, possibly advantageous (at least in terms of metastasis-free survival) for PSA rates over 0.6 ng/ml, taking into account life expectancy and cardiovascular comorbidities. Intensified regimens, for instance, with new-generation hormone therapies, could further improve outcomes in carefully selected patients. Finally, recent advances in molecular imaging, as well as upcoming breakthroughs in genomics and artificial intelligence tools, could soon reshuffle the cards of the current therapeutic strategy.},
keywords = {cancer, out_lab, Prostate cancer, radiotherapy},
pubstate = {published},
tppubtype = {article}
}
@article{nokey,
title = {Paleo-diatom composition from Santa Barbara Basin deep-sea sediments: a comparison of 18S-V9 and diat-rbcL metabarcoding vs shotgun metagenomics. },
author = {Armbrecht L, Eisenhofer R, Utge J, Sibert EC, Rocha F, Ward R, Pierella Karlusich JJ, Tirichine L, Norris R, Summers M, Bowler C},
doi = {doi: 10.1038/s43705-021-00070-8.},
year  = {2021},
date = {2021-11-09},
urldate = {2021-11-09},
journal = {ISME Commun},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34831016,
title = {The Release of Inflammatory Mediators from Acid-Stimulated Mesenchymal Stromal Cells Favours Tumour Invasiveness and Metastasis in Osteosarcoma},
author = {Sofia Avnet and Silvia Lemma and Margherita Cortini and Gemma Di Pompo and Francesca Perut and Maria Veronica Lipreri and Laura Roncuzzi and Marta Columbaro and Costantino Errani and Alessandra Longhi and Nicoletta Zini and Dominique Heymann and Massimo Dominici and Giulia Grisendi and Giulia Golinelli and Lorena Consolino and Dario Livio Longo and Cristina Nanni and Alberto Righi and Nicola Baldini},
doi = {10.3390/cancers13225855},
issn = {2072-6694},
year  = {2021},
date = {2021-11-01},
urldate = {2021-11-01},
journal = {Cancers (Basel)},
volume = {13},
number = {22},
abstract = {Osteosarcoma is the most frequent primary malignant bone tumour with an impressive tendency to metastasise. Highly proliferative tumour cells release a remarkable amount of protons into the extracellular space that activates the NF-kB inflammatory pathway in adjacent stromal cells. In this study, we further validated the correlation between tumour glycolysis/acidosis and its role in metastases. In patients, at diagnosis, we found high circulating levels of inflammatory mediators (IL6, IL8 and miR-136-5p-containing extracellular vesicles). IL6 serum levels significantly correlated with disease-free survival and F-FDG PET/CT uptake, an indirect measurement of tumour glycolysis and, hence, of acidosis. In vivo subcutaneous and orthotopic models, co-injected with mesenchymal stromal (MSC) and osteosarcoma cells, formed an acidic tumour microenvironment (mean pH 6.86, as assessed by in vivo MRI-CEST pH imaging). In these xenografts, we enlightened the expression of both IL6 and the NF-kB complex subunit in stromal cells infiltrating the tumour acidic area. The co-injection with MSC also significantly increased lung metastases. Finally, by using 3D microfluidic models, we directly showed the promotion of osteosarcoma invasiveness by acidosis via IL6 and MSC. In conclusion, osteosarcoma-associated MSC react to intratumoural acidosis by triggering an inflammatory response that, in turn, promotes tumour invasiveness at the primary site toward metastasis development.},
keywords = {cancer, out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{10.3389/fphys.2021.712593,
title = {An Expanded Survey of the Moth PBP/GOBP Clade in Bombyx mori: New Insight into Expression and Functional Roles},
author = {Xia Guo and Ning Xuan and Guoxia Liu and Hongyan Xie and Qinian Lou and Philippe Arnaud and Bernard Offmann and Jean-François Picimbon},
url = {https://www.frontiersin.org/article/10.3389/fphys.2021.712593},
doi = {10.3389/fphys.2021.712593},
issn = {1664-042X},
year  = {2021},
date = {2021-10-28},
urldate = {2021-01-01},
journal = {Frontiers in Physiology},
volume = {12},
pages = {1701},
abstract = {We studied the expression profile and ontogeny (from the egg stage through the larval stages and pupal stages, to the elderly adult age) of four OBPs from the silkworm moth Bombyx mori. We first showed that male responsiveness to female sex pheromone in the silkworm moth B. mori does not depend on age variation; whereas the expression of BmorPBP1, BmorPBP2, BmorGOBP1, and BmorGOBP2 varies with age. The expression profile analysis revealed that the studied OBPs are expressed in non-olfactory tissues at different developmental stages. In addition, we tested the effect of insecticide exposure on the expression of the four OBPs studied. Exposure to a toxic macrolide insecticide endectocide molecule (abamectin) led to the modulated expression of all four genes in different tissues. The higher expression of OBPs was detected in metabolic tissues, such as the thorax, gut, and fat body. All these data strongly suggest some alternative functions for these proteins other than olfaction. Finally, we carried out ligand docking studies and reported that PBP1 and GOBP2 have the capacity of binding vitamin K1 and multiple different vitamins.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{cancers13215402,
title = {Voluntary Wheel Running Does Not Enhance Radiotherapy Efficiency in a Preclinical Model of Prostate Cancer: The Importance of Physical Activity Modalities?},
author = {Suzanne Dufresne and Cindy Richard and Arthur Dieumegard and Luz Orfila and Gregory Delpon and Sophie Chiavassa and Brice Martin and Laurent Rouvière and Jean-Michel Escoffre and Edward Oujagir and Baudouin Denis de Senneville and Ayache Bouakaz and Nathalie Rioux-Leclercq and Vincent Potiron and Amélie Rébillard},
url = {https://www.mdpi.com/2072-6694/13/21/5402},
doi = {10.3390/cancers13215402},
issn = {2072-6694},
year  = {2021},
date = {2021-10-28},
urldate = {2021-01-01},
journal = {Cancers},
volume = {13},
number = {21},
abstract = {Physical activity is increasingly recognized as a strategy able to improve cancer patient outcome, and its potential to enhance treatment response is promising, despite being unclear. In our study we used a preclinical model of prostate cancer to investigate whether voluntary wheel running (VWR) could improve tumor perfusion and enhance radiotherapy (RT) efficiency. Nude athymic mice were injected with PC-3 cancer cells and either remained inactive or were housed with running wheels. Apparent microbubble transport was enhanced with VWR, which we hypothesized could improve the RT response. When repeating the experiments and adding RT, however, we observed that VWR did not influence RT efficiency. These findings contrasted with previous results and prompted us to evaluate if the lack of effects observed on tumor growth could be attributable to the physical activity modality used. Using PC-3 and PPC-1 xenografts, we randomized mice to either inactive controls, VWR, or treadmill running (TR). In both models, TR (but not VWR) slowed down tumor growth, suggesting that the anti-cancer effects of physical activity are dependent on its modalities. Providing a better understanding of which activity type should be recommended to cancer patients thus appears essential to improve treatment outcomes.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34391651,
title = {[Postoperative radiotherapy for prostate cancer: when to propose it? What is the place for androgen deprivation?]},
author = {N Benziane-Ouaritini and P Sargos and J B Beauval and S Supiot and I Latorzeff},
doi = {10.1016/j.canrad.2021.07.005},
issn = {1769-6658},
year  = {2021},
date = {2021-10-25},
urldate = {2021-10-01},
journal = {Cancer Radiother},
volume = {25},
number = {6-7},
pages = {667--673},
abstract = {PURPOSE: While there is no high-level evidence showing superiority of surgery over radiation treatment, radical prostatectomy is the most common treatment option for patients with localized, non-metastatic disease. Nearly 30% of all patients undergoing surgery will develop a biochemical recurrence in 10 years. In fact, more than 30% of contemporary patients treated with RP will harbor aggressive disease characteristics at final pathology.

MATERIAL AND MEHODS: We conducted a review of the literature evaluating the timing of radiotherapy and the place of androgen deprivation after prostatectomie totale.

RESULTS: Four trials randomizing adjuvant radiotherapy and surveillance found an advantage in biochemical relapse-free survival in favor of immediate irradiation after radical prostatectomy, called adjuvant. However, in these studies, more than 40% of patients in the arm without adjuvant radiotherapy did not relapse at 10 years of follow-up. More recently, the question of the optimal time of this post-operative, adjuvant RT or during biological relapse has arisen through three trials (RADICALS-RT, RAVES, GETUG-AFU 17). These trials did not show a benefit for adjuvant radiotherapy in terms of event-free survival, a PSA-based endpoint, while confirming the toxicities observed during irradiation immediately after surgery. The optimal duration of hormonal therapy when associated with post-prostatectomy radiation therapy remains controversial.

CONCLUSION: Early salvage radiotherapy is a new standard of treatment and adjuvant radiotherapy could be reserved for very selected patients. The role of hormone therapy is well defined in salvage situation, but its duration is still being studied.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34391648,
title = {[Combination radiotherapy-immunotherapy in genitourinary cancer]},
author = {L Ollivier and V Guimas and E Rio and L Vaugier and I Masson and V Libois and M Labbé and D Fradin and V Potiron and S Supiot},
doi = {10.1016/j.canrad.2021.06.033},
issn = {1769-6658},
year  = {2021},
date = {2021-10-21},
urldate = {2021-10-01},
journal = {Cancer Radiother},
volume = {25},
number = {6-7},
pages = {565--569},
abstract = {Immunotherapy occupies a growing place in urologic oncology, mainly for kidney and bladder cancers. On the basis of encouraging preclinical work, the combination of immunotherapy with radiotherapy aims to increase the tumor response, including in metastatic tumors, which raises many hopes, which this article reviews.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{bertorelle2021tailoring,
title = {Tailoring NIR-II photoluminescence of single thiolated Au25 nanoclusters by selective binding to proteins},
author = {Franck Bertorelle and David Wegner and Martina Perić Bakulić and Hussein Fakhouri and Clothilde Comby-Zerbino and Amin Sagar and Pau Bernadó and Ute Resch-Genger and Vlasta Bonačić Koutecky Koutecky and Xavier Le Guével and Rodolphe Antoine},
doi = {10.21203/rs.3.rs-958149/v1},
year  = {2021},
date = {2021-10-21},
urldate = {2021-10-21},
journal = {Research Square},
abstract = {Atomically precise gold nanoclusters (Au NCs) are a fascinating class of nanomaterials that exhibit molecule-like properties and have outstanding photoluminescence (PL), which is highly dependent on their structure and chemical environment. Their ultrasmall size, molecular chemistry, and biocompatibility make them extremely appealing for selective biomolecule labeling in investigations of biological mechanisms at the cellular and anatomical levels. In this work, we report a simple route to incorporating a preformed Au25 nanocluster into a model bovine serum albumin (BSA) protein. A new approach combining small-angle X-ray scattering and molecular modeling provides a clear localization of a single Au25 within the protein to a cysteine residue on the gold nanocluster surface. Attaching Au25 to BSA strikingly modifies the PL properties with enhancement and a redshift in the second near-infrared window (NIR-II). An extensive study based on a bottom-up approach that uses mixed-ligand nanoclusters Au25pMBA(18−x)Cysx with x=2, 5, 18 supported by experimental data (steady state, time-resolved spectroscopy) and theoretical calculations (DFT) provides new hints at the origin of NIR-II emission in such nanoclusters and their subsequent enhancement when selectively binding to a cysteine-rich protein. This study paves the way to controlling the design of selectively sensitive probes in biomolecules through a ligand-based strategy to enable the optical detection of biomolecules in a cellular environment by live imaging.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34307011,
title = { three-dimensional cell cultures for bone sarcomas},
author = {Javier Munoz-Garcia and Camille Jubelin and Aurélie Loussouarn and Matisse Goumard and Laurent Griscom and Axelle Renodon-Cornière and Marie-Françoise Heymann and Dominique Heymann},
doi = {10.1016/j.jbo.2021.100379},
issn = {2212-1366},
year  = {2021},
date = {2021-10-01},
journal = {J Bone Oncol},
volume = {30},
pages = {100379},
abstract = {Bone sarcomas are rare tumour entities that arise from the mesenchyme most of which are highly heterogeneous at the cellular, genetic and epigenetic levels. The three main types are osteosarcoma, Ewing sarcoma, and chondrosarcoma. These oncological entities are characterised by high morbidity and mortality and an absence of significant therapeutic improvement in the last four decades. In the field of oncology,  cultures of cancer cells have been extensively used for drug screening unfortunately with limited success. Indeed, despite the massive knowledge acquired from conventional 2D culture methods, scientific community has been challenged by the loss of efficacy of drugs when moved to clinical trials. The recent explosion of new 3D culture methods is paving the way to more relevant  models mimicking the  tumour environment (e.g. bone structure) with biological responses close to the  context. The present review gives a brief overview of the latest advances of the 3D culture methods used for studying primary bone sarcomas.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
@article{munoz2021vitro,
title = {In vitro three-dimensional cell cultures for bone sarcomas},
author = {Javier Muñoz-Garcia and Camille Jubelin and Aurélie Loussouarn and Matisse Goumard and Laurent Griscom and Axelle Renodon-Cornière and Marie-Françoise Heymann and Dominique Heymann},
editor = {Elsevier},
doi = {10.1016/j.jbo.2021.100379},
issn = {2212-1374},
year  = {2021},
date = {2021-10-01},
urldate = {2021-10-01},
journal = {Journal of Bone Oncology},
volume = {30},
pages = {100379},
publisher = {Elsevier},
abstract = {Bone sarcomas are rare tumour entities that arise from the mesenchyme most of which are highly heterogeneous at the cellular, genetic and epigenetic levels. The three main types are osteosarcoma, Ewing sarcoma, and chondrosarcoma. These oncological entities are characterised by high morbidity and mortality and an absence of significant therapeutic improvement in the last four decades. In the field of oncology, in vitro cultures of cancer cells have been extensively used for drug screening unfortunately with limited success. Indeed, despite the massive knowledge acquired from conventional 2D culture methods, scientific community has been challenged by the loss of efficacy of drugs when moved to clinical trials. The recent explosion of new 3D culture methods is paving the way to more relevant in vitro models mimicking the in vivo tumour environment (e.g. bone structure) with biological responses close to the in vivo context. The present review gives a brief overview of the latest advances of the 3D culture methods used for studying primary bone sarcomas.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{velic_molecular_2021,
title = {Molecular Determinant of DIDS Analogs Targeting RAD51 Activity},
author = {Denis Velic and Alexandre Demeyer and Thibaut Peterlini and Houda Benhelli-Mokrani and Monique Mathé-Allainmat and Jean-Yves Masson and Fabrice Fleury},
url = {https://www.mdpi.com/1420-3049/26/18/5460},
doi = {10.3390/molecules26185460},
issn = {1420-3049},
year  = {2021},
date = {2021-09-15},
urldate = {2021-09-15},
journal = {Molecules},
volume = {26},
number = {18},
pages = {5460},
abstract = {RAD51 is the central protein in DNA repair by homologous recombination (HR), involved in several steps of this process. It is shown that overexpression of the RAD51 protein is correlated with increased survival of cancer cells to cancer treatments. For the past decade, RAD51 overexpression-mediated resistance has justiﬁed the development of targeted inhibitors. One of the ﬁrst molecules described to inhibit RAD51 was the 4,4 -diisothiocyanato-stilbene-2,2 -disulfonic acid (DIDS) molecule. This small molecule is effective in inhibiting different functions of RAD51, however its mode of action and the chemical functions involved in this inhibition have not been identiﬁed. In this work, we used several commercial molecules derived from DIDS to characterize the structural determinants involved in modulating the activity of RAD51. By combining biochemical and biophysical approaches, we have shown that DIDS and two analogs were able to inhibit the binding of RAD51 to ssDNA and prevent the formation of D-loop by RAD51. Both isothiocyanate substituents of DIDS appear to be essential in the inhibition of RAD51. These results open the way to the synthesis of new molecules derived from DIDS that should be greater modulators of RAD51 and more efﬁcient for HR inhibition.},
keywords = {piramid, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{demeyer_inhibiting_2021,
title = {Inhibiting homologous recombination by targeting RAD51 protein},
author = {Alexandre Demeyer and Houda Benhelli-Mokrani and B. Chénais and Pierre Weigel and Fabrice Fleury},
url = {https://linkinghub.elsevier.com/retrieve/pii/S0304419X21000949},
doi = {10.1016/j.bbcan.2021.188597},
issn = {0304419X},
year  = {2021},
date = {2021-09-15},
urldate = {2021-09-15},
journal = {Biochimica et Biophysica Acta (BBA) - Reviews on Cancer},
volume = {1876},
number = {2},
pages = {188597},
abstract = {Homologous recombination (HR) is involved in repairing DNA double-strand breaks (DSB), the most harmful for the cell. Regulating HR is essential for maintaining genomic stability. In many forms of cancer, overactivation of HR increases tumor resistance to DNA-damaging treatments. RAD51, HR&#039;s core protein, is very often overexpressed in these cancers and plays a critical role in cancer cell development and survival. Targeting RAD51 directly to reduce its activity and its expression is therefore one strategy to sensitize and overcome resistance cancer cells to existing DNA-damaging therapies which remains the limiting factor for the success of targeted therapy.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{le_untargeted_2021,
title = {Untargeted Metabolomics Approach for the Discovery of Environment-Related Pyran-2-Ones Chemodiversity in a Marine-Sourced Penicillium restrictum},
author = {Van-Tuyen Le and Samuel Bertrand and Thibaut Robiou du Pont and Fabrice Fleury and Nathalie Caroff and Sandra Bourgeade-Delmas and Emmanuel Gentil and Cedric Logé and Gregory Genta-Jouve and Olivier Grovel},
url = {https://www.mdpi.com/1660-3397/19/7/378},
doi = {10.3390/md19070378},
issn = {1660-3397},
year  = {2021},
date = {2021-09-15},
journal = {Marine Drugs},
volume = {19},
number = {7},
pages = {378},
abstract = {Very little is known about chemical interactions between fungi and their mollusc host within marine environments. Here, we investigated the metabolome of a Penicillium restrictum MMS417 strain isolated from the blue mussel Mytilus edulis collected on the Loire estuary, France. Following the OSMAC approach with the use of 14 culture media, the effect of salinity and of a musselderived medium on the metabolic expression were analysed using HPLC-UV/DAD-HRMS/MS. An untargeted metabolomics study was performed using principal component analysis (PCA), orthogonal projection to latent structure discriminant analysis (O-PLSDA) and molecular networking (MN). It highlighted some compounds belonging to sterols, macrolides and pyran-2-ones, which were speciﬁcally induced in marine conditions. In particular, a high chemical diversity of pyran-2-ones was found to be related to the presence of mussel extract in the culture medium. Mass spectrometry (MS)- and UV-guided puriﬁcation resulted in the isolation of ﬁve new natural fungal pyran-2-one derivatives—5,6-dihydro-6S-hydroxymethyl-4-methoxy-2H-pyran-2-one (1), (6S, 1’R, 2’S)-LL-P880β (3), 5,6-dihydro-4-methoxy-6S-(1’S, 2’S-dihydroxy pent-3’(E)-enyl)-2H-pyran-2-one (4), 4-methoxy-6(1’R, 2’S-dihydroxy pent-3’(E)-enyl)-2H-pyran-2-one (6) and 4-methoxy-2H-pyran-2-one (7)—together with the known (6S, 1’S, 2’S)-LL-P880β (2), (1’R, 2’S)-LL-P880γ (5), 5,6-dihydro-4-methoxy-2H-pyran2-one (8), (6S, 1’S, 2’R)-LL-P880β (9), (6S, 1’S)-pestalotin (10), 1’R-dehydropestalotin (11) and 6-pentyl4-methoxy-2H-pyran-2-one (12) from the mussel-derived culture medium extract. The structures of 1-12 were determined by 1D- and 2D-MMR experiments as well as high-resolution tandem MS, ECD and DP4 calculations. Some of these compounds were evaluated for their cytotoxic, antibacterial, antileishmanial and in-silico PTP1B inhibitory activities. These results illustrate the utility in using host-derived media for the discovery of new natural products.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{cabezas2021modulation,
title = {Modulation of the Activity and Regioselectivity of a Glycosidase: Development of a Convenient Tool for the Synthesis of Specific Disaccharides},
author = {Yari Cabezas-Pérusse and Franck Daligault and Vincent Ferrières and Olivier Tasseau and Sylvain Tranchimand},
url = {https://www.mdpi.com/1420-3049/26/18/5445},
doi = {10.3390/molecules26185445},
year  = {2021},
date = {2021-09-07},
urldate = {2021-09-07},
journal = {Molecules},
volume = {26},
number = {18},
pages = {5445},
publisher = {MDPI},
abstract = {The synthesis of disaccharides, particularly those containing hexofuranoside rings, requires a large number of steps by classical chemical means. The use of glycosidases can be an alternative to limit the number of steps, as they catalyze the formation of controlled glycosidic bonds starting from simple and easy to access building blocks; the main drawbacks are the yields, due to the balance between the hydrolysis and transglycosylation of these enzymes, and the enzyme-dependent regioselectivity. To improve the yield of the synthesis of β-d-galactofuranosyl-(1→X)-d-mannopyranosides catalyzed by an arabinofuranosidase, in this study we developed a strategy to mutate, then screen the catalyst, followed by a tailored molecular modeling methodology to rationalize the effects of the identified mutations. Two mutants with a 2.3 to 3.8-fold increase in transglycosylation yield were obtained, and in addition their accumulated regioisomer kinetic profiles were very different from the wild-type enzyme. Those differences were studied in silico by docking and molecular dynamics, and the methodology revealed a good predictive quality in regards with the regioisomer profiles, which is in good agreement with the experimental transglycosylation kinetics. So, by engineering CtAraf51, new biocatalysts were enabled to obtain the attractive central motif from the Leishmania lipophosphoglycan core with a higher yield and regioselectivity.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34503149,
title = {Stereotactic Re-Irradiation for Local Recurrence after Radical Prostatectomy and Radiation Therapy: A Retrospective Multicenter Study},
author = {Tanguy Perennec and Loig Vaugier and Alain Toledano and Nathaniel Scher and Astrid Thomin and Yoann Pointreau and Guillaume Janoray and Renaud De Crevoisier and Stéphane Supiot},
doi = {10.3390/cancers13174339},
issn = {2072-6694},
year  = {2021},
date = {2021-08-01},
urldate = {2021-08-01},
journal = {Cancers (Basel)},
volume = {13},
number = {17},
abstract = {Prostate cancer recurrence in patients previously treated with radical prostatectomy and radiation therapy is challenging. Re-irradiation could be an option, but data regarding efficacy and safety are lacking. We retrospectively evaluated salvage re-irradiation for local recurrence after prostatectomy and external beam radiation therapy. We collected data from 48 patients who underwent salvage reirradiation with stereotactic radiation therapy for local prostate cancer recurrence in the prostatic bed at four French centers. Fifteen patients (31%) were on androgen deprivation therapy during stereotactic radiotherapy. Biochemical response and relapse-free survival were analyzed, and post-treatment toxicities were assessed according to the Common Terminology of Adverse Events criteria. Five patients had grade 3 late bladder toxicity (cystitis), three had grade 3 late incontinence, and one had grade 3 late chronic pain. At three months, 83% of patients had a positive biochemical response. The median follow-up was 22 months. At the end of the follow-up, 21 patients (43%) had a biochemical relapse. The median time to biologic relapse was 27 months. The biochemical relapse rates at 1 and 2 years were 80% and 52%, respectively. In conclusion, salvage re-irradiation for recurrent prostate cancer in the prostate bed may generate significant toxicity rates, and a prospective study with appropriate patient selection is needed to evaluate its effectiveness.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34221983,
title = {Late Gastrointestinal Tolerance After Prostate Radiotherapy: Is the Anal Canal the Culprit? A Narrative Critical Review},
author = {Paul Sargos and Mame Daro Faye and Manon Bacci and Stéphane Supiot and Igor Latorzeff and David Azria and Tamim M Niazi and Te Vuong and Véronique Vendrely and Renaud de Crevoisier},
doi = {10.3389/fonc.2021.666962},
issn = {2234-943X},
year  = {2021},
date = {2021-06-16},
urldate = {2021-01-01},
journal = {Front Oncol},
volume = {11},
pages = {666962},
abstract = {Introduction: Late gastro-intestinal toxicities (LGIT) secondary to pelvic radiotherapy (RT) are well described in the literature. LGIT are mainly related to rectal or ano-rectal irradiation; however, involvement of the anal canal (AC) in the occurrence of LGIT remains poorly described and understood.

Materials and Methods: The aim of this work was to explore the potential role of the AC in the development of LGIT after prostate irradiation and identify predictive factors that could be optimized in order to limit these toxicities. This narrative literature review was realized using the Pubmed database. We identified original articles published between June 1997 and July 2019, relating to LGIT after RT for localized prostate cancer and for which AC was identified independently. Articles defining the AC as part of an anorectal or rectal volume only were excluded.

Results: A history of abdominal surgery or cardio-vascular risk, anticoagulant or tobacco use, and the occurrence of acute GIT during RT increases the risk of LGIT. A dose-effect relationship was identified between dose to the AC and development of LGIT. Identification and contouring of the AC and adjacent anatomical structures (muscles or nerves) are justified to apply specific dose constraints. As a limitation, our review mainly considered on 3DCRT which is no longer the standard of care nowadays; we did not identify any reports in the literature using moderately hypofractionated RT for the prostate and AC specific dosimetry.

Conclusion: These results suggest that the AC may have an important role in the development of LGIT after pelvic RT for prostate cancer. The individualization of the AC during planning should be recommended in prospective studies.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{https://doi.org/10.1111/1462-2920.15592,
title = {Virulence of Vibrio harveyi ORM4 toward the European abalone Haliotis tuberculata involves both quorum sensing and a type III secretion system},
author = {Amandine Morot and Sahar El Fekih and Adeline Bidault and Alizée Le Ferrand and Albane Jouault and Javid Kavousi and Alexis Bazire and Vianney Pichereau and Alain Dufour and Christine Paillard and François Delavat},
url = {https://sfamjournals.onlinelibrary.wiley.com/doi/abs/10.1111/1462-2920.15592
hal-04209594v1 },
doi = {https://doi.org/10.1111/1462-2920.15592},
year  = {2021},
date = {2021-05-14},
urldate = {2021-05-14},
journal = {Environmental Microbiology},
volume = {23},
number = {9},
pages = {5273-5288},
abstract = {Abstract Environmental Vibrio strains represent a major threat in aquaculture, but the understanding of their virulence mechanisms heavily relies on the transposition of knowledge from human-pathogen vibrios. Here, the genetic bases of the virulence of Vibrio harveyi ORM4 toward the European abalone Haliotis tuberculata were characterized. We demonstrated that luxO, encoding a major regulator of the quorum sensing system, is crucial for the virulence of this strain, and that its deletion leads to a decrease in swimming motility, biofilm formation, and exopolysaccharide production. Furthermore, the biofilm formation by V. harveyi ORM4 was increased by abalone serum, which required LuxO. The absence of LuxO in V. harveyi ORM4 yielded opposite phenotypes compared with other Vibrio species including V. campbellii (still frequently named V. harveyi). In addition, we report a full Type III Secretion System (T3SS) gene cluster in the V. harveyi ORM4 genome. LuxO was shown to negatively regulate the promoter activity of exsA, encoding the major regulator of the T3SS genes, and the deletion of exsA abolished the virulence of V. harveyi ORM4. These results unveil virulence mechanisms set up by this environmentally important bacterial pathogen, and pave the way for a better molecular understanding of the regulation of its pathogenicity. This article is protected by copyright. All rights reserved.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{combes2021functionalized,
title = {Functionalized Au 15 nanoclusters as luminescent probes for protein carbonylation detection},
author = {Guillaume F. Combes and Hussein Fakhouri and Christophe Moulin and Marion Girod and Franck Bertorelle and Srestha Basu and Romain Ladouce and Martina Perić Bakulić and Željka Sanader Maršić and Isabelle Russier-Antoine and Pierre-François Brevet and Philippe Dugourd and Anita Krisko and Katarina Trajković and Miroslav Radman and Vlasta Bonačić-Koutecký and Rodolphe Antoine},
doi = {10.1038/s42004-021-00497-z},
year  = {2021},
date = {2021-05-14},
urldate = {2021-05-14},
journal = {Communications Chemistry},
volume = {4},
number = {1},
pages = {1--11},
publisher = {Nature Publishing Group},
abstract = {Atomically precise, ligand-protected gold nanoclusters (AuNCs) attract considerable attention as contrast agents in the biosensing field. However, the control of their optical properties and functionalization of surface ligands remain challenging. Here we report a strategy to tailor AuNCs for the precise detection of protein carbonylation—a causal biomarker of ageing. We produce Au15SG13 (SG for glutathione) with atomic precision and functionalize it with a thiolated aminooxy moiety to impart protein carbonyl-binding properties. Mass spectrometry and molecular modelling reveal the key structural features of Au15SG12-Aminooxy and its reactivity towards carbonyls. Finally, we demonstrate that Au15SG12-Aminooxy detects protein carbonylation in gel-based 1D electrophoresis by one- and two-photon excited fluorescence. Importantly, to our knowledge, this is the first application of an AuNC that detects a post-translational modification as a nonlinear optical probe. The significance of post-translational modifications in life sciences may open avenues for the use of Au15SG13 and other nanoclusters as contrast agents with tailored surface functionalization and optical properties.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34062831,
title = {ICG-001, an Inhibitor of the β-Catenin and cAMP Response Element-Binding Protein Dependent Gene Transcription, Decreases Proliferation but Enhances Migration of Osteosarcoma Cells},
author = {Geoffroy Danieau and Sarah Morice and Sarah Renault and Régis Brion and Kevin Biteau and Jérôme Amiaud and Marie Cadé and Dominique Heymann and Frédéric Lézot and Franck Verrecchia and Françoise Rédini and Bénédicte Brounais-Le Royer},
doi = {10.3390/ph14050421},
issn = {1424-8247},
year  = {2021},
date = {2021-05-01},
urldate = {2021-05-01},
journal = {Pharmaceuticals (Basel)},
volume = {14},
number = {5},
abstract = {High-grade osteosarcomas are the most frequent malignant bone tumors in the pediatric population, with 150 patients diagnosed every year in France. Osteosarcomas are associated with low survival rates for high risk patients (metastatic and relapsed diseases). Knowing that the canonical Wnt signaling pathway (Wnt/β-catenin) plays a complex but a key role in primary and metastatic development of osteosarcoma, the aim of this work was to analyze the effects of ICG-001, a CBP/β-catenin inhibitor blocking the β-catenin dependent gene transcription, in three human osteosarcoma cell lines (KHOS, MG63 and 143B). The cell proliferation and migration were first evaluated in vitro after ICG-001 treatment. Secondly, a mouse model of osteosarcoma was used to establish the in vivo biological effect of ICG-001 on osteosarcoma growth and metastatic dissemination. In vitro, ICG-001 treatment strongly inhibits osteosarcoma cell proliferation through a cell cycle blockade in the G0/G1 phase, but surprisingly, increases cell migration of the three cell lines. Moreover, ICG-001 does not modulate tumor growth in the osteosarcoma mouse model but, rather significantly increases the metastatic dissemination to lungs. Taken together, these results highlight, despite an anti-proliferative effect, a deleterious pro-migratory role of ICG-001 in osteosarcoma.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{https://doi.org/10.1002/chem.202100110,
title = {Rational Enzyme Design without Structural Knowledge: A Sequence-Based Approach for Efficient Generation of Transglycosylases},
author = {David Teze and Jiao Zhao and Mathias Wiemann and Kazi Z G Ara and Rossana Lupo and Birgitte Zeuner and Marlène Vuillemin and Mette E Rønne and Göran Carlström and Jens Ø Duus and Yves-Henri Sanejouand and Michael J O&#039;Donohue and Eva Nordberg Karlsson and Régis Fauré and Henrik Stålbrand and Birte Svensson},
url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202100110},
doi = {https://doi.org/10.1002/chem.202100110},
issn = {0947-6539, 1521-3765},
year  = {2021},
date = {2021-04-29},
urldate = {2021-04-29},
journal = {Chemistry – A European Journal},
volume = {27},
number = {40},
pages = {10323--10334},
abstract = {Glycobiology is dogged by the relative scarcity of synthetic, defined oligosaccharides. Enzyme-catalysed glycosylation using glycoside hydrolases is feasible but is hampered by the innate hydrolytic activity of these enzymes. Protein engineering is useful to remedy this, but it usually requires prior structural knowledge of the target enzyme, and/or relies on extensive, time-consuming screening and analysis. Here we describe a straightforward strategy that involves rational rapid in silico analysis of protein sequences. The method pinpoints 6‒12 single mutant candidates to improve transglycosylation yields. Requiring very little prior knowledge of the target enzyme other than its sequence, the method is generic and procures catalysts for the formation of glycosidic bonds involving various d / l -, α/β-pyranosides or furanosides, and exo - and endo -action. Moreover, mutations validated in one enzyme can be transposed to others, even distantly related enzymes.},
keywords = {Glycoside hydrolase, multiple sequences alignment, oligosaccharide synthesis, protein engineering, team 1, Transglycosylation},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33920758,
title = {A Monte Carlo Determination of Dose and Range Uncertainties for Preclinical Studies with a Proton Beam},
author = {Arthur Bongrand and Charbel Koumeir and Daphnée Villoing and Arnaud Guertin and Ferid Haddad and Vincent Métivier and Freddy Poirier and Vincent Potiron and Noël Servagent and Stéphane Supiot and Grégory Delpon and Sophie Chiavassa},
doi = {10.3390/cancers13081889},
issn = {2072-6694},
year  = {2021},
date = {2021-04-15},
urldate = {2021-04-01},
journal = {Cancers (Basel)},
volume = {13},
number = {8},
abstract = {Proton therapy (PRT) is an irradiation technique that aims at limiting normal tissue damage while maintaining the tumor response. To study its specificities, the ARRONAX cyclotron is currently developing a preclinical structure compatible with biological experiments. A prerequisite is to identify and control uncertainties on the ARRONAX beamline, which can lead to significant biases in the observed biological results and dose-response relationships, as for any facility. This paper summarizes and quantifies the impact of uncertainty on proton range, absorbed dose, and dose homogeneity in a preclinical context of cell or small animal irradiation on the Bragg curve, using Monte Carlo simulations. All possible sources of uncertainty were investigated and discussed independently. Those with a significant impact were identified, and protocols were established to reduce their consequences. Overall, the uncertainties evaluated were similar to those from clinical practice and are considered compatible with the performance of radiobiological experiments, as well as the study of dose-response relationships on this proton beam. Another conclusion of this study is that Monte Carlo simulations can be used to help build preclinical lines in other setups.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33921595,
title = {Electrochromic Properties and Electrochemical Behavior of Marennine, a Bioactive Blue-Green Pigment Produced by the Marine Diatom },
author = {Nellie Francezon and Mickaël Herbaut and Jean-François Bardeau and Charles Cougnon and William Bélanger and Réjean Tremblay and Boris Jacquette and Jens Dittmer and Jean-Bernard Pouvreau and Jean-Luc Mouget and Pamela Pasetto},
doi = {10.3390/md19040231},
issn = {1660-3397},
year  = {2021},
date = {2021-04-01},
urldate = {2021-04-01},
journal = {Mar Drugs},
volume = {19},
number = {4},
abstract = {Marennine has long been known as the unique peculiar pigment responsible for the natural greening of oysters. It is specifically produced by the marine diatom  and it is a natural blue molecule indeed promising for food industry because of the rarity of such non-toxic, blue-colored pigments. In the search for its still not defined molecular structure, investigation of the color changes with the redox state has been carried out combining different approaches. Reducing and oxidizing chemicals have been added to purified marennine solutions and a stable blue-green color has been confirmed for the oxidized state, while a yellow color corresponded to the reduced unstable state. Raman spectroscopy has been used to monitor changes in the Raman spectra corresponding to the different colored states, and cyclic voltammetry has allowed the detection of a redox system in which protons and electrons are exchanged. These findings show that marennine is a suitable stable blue pigment for use in food applications and help in the elucidation of the chromophore structure.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{robla_chitosan-based_2021,
title = {A chitosan-based nanosystem as pneumococcal vaccine delivery platform},
author = {Sandra Robla and Maruthi Prasanna and Rubén Varela-Calviño and Cyrille Grandjean and Noemi Csaba},
url = {https://doi.org/10.1007/s13346-021-00928-3},
doi = {10.1007/s13346-021-00928-3},
issn = {2190-3948},
year  = {2021},
date = {2021-04-01},
urldate = {2021-06-16},
journal = {Drug Delivery and Translational Research},
volume = {11},
number = {2},
pages = {581--597},
abstract = {Chitosan-based nanosystems have been described as interesting tools for antigen delivery and for enhancing the immunogenicity of nasally administered vaccines. As a possible vaccine delivery method, the chemical conjugation of chitosan nanocapsules with the Streptococcus pneumoniae cell membrane protein PsaA (pneumococcal surface adhesin A) is suggested here. The antigen PsaA, common to all pneumococcus serotypes, is expected to improve its uptake by immune cells and to activate specific T cells, generating an adaptive immune response against pneumococcus. With this aim, chitosan nanocapsules with thiol-maleimide conjugation between the polymer (chitosan) and the antigen (PsaA) were designed to enable the surface presentation of PsaA for immune cell recognition. Spherical-shaped particles, with a size of 266 ± 32 nm, positive charge of +30 ± 1 mV, and good stability profiles in simulated nasal fluids (up to 24 h) were achieved. PsaA association rates were three times higher compared with nanocapsules without covalent polymer-protein conjugation. Cytotoxicity studies in cell culture media showed non-toxic effect under 150 µg/mL concentration of nanocapsules, and subsequent studies on the maturation of immature dendritic cells in the presence of antigen-conjugated nanocapsules displayed peripheral blood mononuclear cell activation and lymphocyte differentiation after their presentation by dendritic cells. Secretion of TNFα following exposure to nanocapsules and the ability of nanocapsules to activate CD4 and CD8 T lymphocytes had also been studied.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33186618,
title = {Prostate Bed Delineation Guidelines for Postoperative Radiation Therapy: On Behalf Of The Francophone Group of Urological Radiation Therapy},
author = {Sophie Robin and Marjory Jolicoeur and Samuel Palumbo and Thomas Zilli and Gilles Crehange and Olivier De Hertogh and Talar Derashodian and Paul Sargos and Carl Salembier and Stéphane Supiot and Corina Udrescu and Olivier Chapet},
doi = {10.1016/j.ijrobp.2020.11.010},
issn = {1879-355X},
year  = {2021},
date = {2021-04-01},
urldate = {2021-01-01},
journal = {Int J Radiat Oncol Biol Phys},
volume = {109},
number = {5},
pages = {1243--1253},
abstract = {PURPOSE: Prostate bed (PB) irradiation is considered the standard postoperative treatment after radical prostatectomy (RP) for tumors with high-risk features or persistent prostate-specific antigen, or for salvage treatment in case of biological relapse. Four consensus guidelines have been published to standardize practices and reduce the interobserver variability in PB delineation but with discordant recommendations. To improve the reproducibility in the PB delineation, the Francophone Group of Urological Radiotherapy (Groupe Francophone de Radiothérapie Urologique [GFRU]) worked to propose a new and more reproducible consensus guideline for PB clinical target volume (CTV) definition.

METHODS AND MATERIALS: A 4-step procedure was used. First, a group of 10 GFRU prostate experts evaluated the 4 existing delineation guidelines for postoperative radiation therapy (European Organization for Research and Treatment of Cancer; the Faculty of Radiation Oncology Genito-Urinary Group; the Radiation Therapy Oncology Group; and the Princess Margaret Hospital) to identify divergent issues. Second, data sets of 50 magnetic resonance imaging studies (25 after RP and 25 with an intact prostate gland) were analyzed to identify the relevant anatomic boundaries of the PB. Third, a literature review of surgical, anatomic, histologic, and imaging data was performed to identify the relevant PB boundaries. Fourth, a final consensus on PB CTV definition was reached among experts.

RESULTS: Definitive limits of the PB CTV delineation were defined using easily visible landmarks on computed tomography scans (CT). The purpose was to ensure a better reproducibility of PB definition for any radiation oncologist even without experience in postoperative radiation therapy.

CONCLUSIONS: New recommendations for PB delineation based on simple anatomic boundaries and available as a CT image atlas are proposed by the GFRU. Improvement in uniformity in PB CTV definition and treatment homogeneity in the context of clinical trials are expected.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{sanejouand2021normalmode,
title = {Normal-mode driven exploration of protein domain motions},
author = {Yves-Henri Sanejouand},
url = {https://arxiv.org/abs/2103.11959},
doi = {10.1002/jcc.26755},
year  = {2021},
date = {2021-03-22},
urldate = {2021-03-22},
journal = {J. Comput. Chem.},
volume = {42},
pages = {2250},
abstract = {Domain motions involved in the function of proteins can often be well described as a combination of motions along a handfull of low-frequency modes, that is, with the values of a few normal coordinates. This means that, when the functional motion of a protein is unknown, it should prove possible to predict it, since it amounts to guess a few values. However, without the help of additional experimental data, using normal coordinates for generating accurate conformers far away from the initial one is not so straightforward. To do so, a new approach is proposed: instead of building conformers directly with the values of a subset of normal coordinates, they are built in two steps, the conformer built with normal coordinates being just used for defining a set of distance constraints, the final conformer being built so as to match them. Note that this approach amounts to transform the problem of generating accurate protein conformers using normal coordinates into a better known one: the distance-geometry problem, which is herein solved with the help of the ROSETTA software. In the present study, this approach allowed to rebuild accurately six large amplitude conformational changes, using at most six low-frequency normal coordinates. As a consequence of the low-dimensionality of the corresponding subspace, random exploration also proved enough for generating low-energy conformers close to the known end-point of the conformational change of the LAO binding protein, lysozyme T4 and adenylate kinase.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33762148,
title = {Perineal recurrence of prostate cancer along a brachytherapy needle track: A case report},
author = {I Sidibe and M Le Blanc-Onfroy and G Delpon and E Rio and M Crepel and M Lacour and J Rigaud and S Cazin and S Supiot},
doi = {10.1016/j.canrad.2020.06.027},
issn = {1769-6658},
year  = {2021},
date = {2021-03-21},
urldate = {2021-03-21},
journal = {Cancer Radiother},
volume = {25},
number = {5},
pages = {476--479},
abstract = {Metastatic recurrence in an atypical site, such as the perineum, can occur after prostatectomy, cryotherapy, or brachytherapy, but is uncommon. To our knowledge, this is only the third case of perineal recurrence of prostatic cancer along a low dose rate brachytherapy needle track. A 64-year-old man was referred to an urologist with an increased PSA of 6.9ng/mL in December 2008. There were no urinary symptoms. Prostatic biopsies revealed a Gleason 6 adenocarcinoma (3+3), and he was treated with low dose rate brachytherapy in May 2009. Sixty-seven seeds of iodine 125 were loaded under ultrasound control, and the PSA subsequently fell to a nadir of 1.19ng/mL in November 2015. Eight years (May 2017) after the initial treatment, the PSA rose to 5.2ng/mL. Pelvic MRI and choline PET revealed a nodule in the region of the left internal obturator muscle. Nodule biopsies confirmed prostatic origin. This perineal recurrence is thus most likely related to seeding of tumour cells along the track of a brachytherapy needle. To our knowledge, this is only the fourth case of perineal recurrence of prostatic cancer along a low-dose rate brachytherapy needle track. Perineal recurrence of prostatic cancer along a LDR brachytherapy needle track can occur. Improved imaging techniques may help to identify this type of recurrence earlier and optimise treatment.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33806830,
title = {Antiproliferative Properties of Scandium Exopolysaccharide Complexes on Several Cancer Cell Lines},
author = {Javier Muñoz-Garcia and Mattia Mazza and Cyrille Alliot and Corinne Sinquin and Sylvia Colliec-Jouault and Dominique Heymann and Sandrine Huclier-Markai},
doi = {10.3390/md19030174},
issn = {1660-3397},
year  = {2021},
date = {2021-03-01},
urldate = {2021-03-01},
journal = {Mar Drugs},
volume = {19},
number = {3},
abstract = {Antimetastatic properties on both murine and human osteosarcoma cell lines (POS-1 and KHOS) have been evidenced using exopolysaccharide (EPS) derivatives, produced by  bacterium. These derivatives had no significant effect on the cell cycle neither a pro-apoptotic effect on osteosarcoma cells. Based on this observation, these EPSs could be employed as new drug delivery systems for therapeutic uses. A theranostic approach, i.e., combination of a predictive biomarker with a therapeutic agent, has been developed notably by combining with true pair of theranostic radionuclides, such as scandium Sc/Sc. However, it is crucial to ensure that, once complexation is done, the biological properties of the vector remain intact, allowing the molecular tropism of the ligand to recognize its molecular target. It is important to assess if the biological properties of EPS evidenced on osteosarcoma cell lines remain when scandium is complexed to the polymers and can be extended to other cancer cell types. Scandium-EPS complexes were thus tested in vitro on human cell lines: MNNG/HOS osteosarcoma, A375 melanoma, A549 lung adenocarcinoma, U251 glioma, MDA231 breast cancer, and Caco2 colon cancer cells. An xCELLigence Real Cell Time Analysis (RTCA) technology assay was used to monitor for 160 h, the proliferation kinetics of the different cell lines. The tested complexes exhibited an anti-proliferative effect, this effect was more effective compared to EPS alone. This increase of the antiproliferative properties was explained by a change in conformation of EPS complexes due to their polyelectrolyte nature that was induced by complexation. Alterations of both growth factor-receptor signaling, and transmembrane protein interactions could be the principal cause of the antiproliferative effect. These results are very promising and reveal that EPS can be coupled to scandium for improving its biological effects and also suggesting that no major structural modification occurs on the ligand.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Sanejouand_2021,
title = {On the vibrational free energy of hydrated proteins},
author = {Yves-Henri Sanejouand},
url = {https://doi.org/10.1088/1478-3975/abdc0f},
doi = {10.1088/1478-3975/abdc0f},
year  = {2021},
date = {2021-03-01},
urldate = {2021-03-01},
journal = {Physical Biology},
volume = {18},
number = {3},
pages = {036003},
publisher = {IOP Publishing},
abstract = {When the hydration shell of a protein is filled with at least 0.6 gram of water per gram of protein, a significant anti-correlation between the vibrational free energy and the potential energy of energy-minimized conformers is observed. This means that low potential energy, well-hydrated, protein conformers tend to be more rigid than high-energy ones. On the other hand, in the case of CASP target 624, when its hydration shell is filled, a significant energy gap is observed between the crystal structure and the best conformers proposed during the prediction experiment, strongly suggesting that including explicit water molecules may help identifying unlikely conformers among good-looking ones.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33137397,
title = {Towards homogenization of total body irradiation practices in pediatric patients across SIOPE affiliated centers. A survey by the SIOPE radiation oncology working group},
author = {Bianca A W Hoeben and Montserrat Pazos and Michael H Albert and Enrica Seravalli and Mirjam E Bosman and Christoph Losert and Tom Boterberg and Farkhad Manapov and Inna Ospovat and Soraya Mico Milla and Candan Demiroz Abakay and Jacob Engellau and Gregor Kos and Stéphane Supiot and Marc Bierings and Geert O Janssens},
doi = {10.1016/j.radonc.2020.10.032},
issn = {1879-0887},
year  = {2021},
date = {2021-02-01},
urldate = {2021-02-01},
journal = {Radiother Oncol},
volume = {155},
pages = {113--119},
abstract = {BACKGROUND AND PURPOSE: To reduce relapse risk, Total Body Irradiation (TBI) is part of conditioning regimens for hematopoietic stem cell transplantation (HSCT) in pediatric acute leukemia. The study purpose was to evaluate clinical practices regarding TBI, such as fractionation, organ shielding and delivery techniques, among SIOPE affiliated radiotherapy centers.

METHODS: An electronic survey was sent out to 233 SIOPE affiliated centers, containing 57 questions about clinical practice of TBI. Surveys could be answered anonymously.

RESULTS: From over 25 countries, 82 responses were collected. For TBI-performing centers, 40/48 irradiated ≤10 pediatric patients annually (range: 1-2 to &gt;25). Most indications concerned acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Four different fractionation schedules were used, of which 12 Gy in 6 fractions was applied in 91% for ALL and 86% for AML. Dose reduction to the lungs, mostly to a mean dose of 8-10 Gy, was applied by 28/33 centers for ALL and 19/21 centers for AML, in contrast to much less applied dose reduction to the kidneys (7/33 ALL and 7/21 AML), thyroid (2/33 ALL and 2/21 AML), liver (4/33 ALL and 3/21 AML) and lenses (4/33 ALL and 4/21 AML). Conventional TBI techniques were used by 24/29 responding centers, while 5/29 used advanced optimized planning techniques.

CONCLUSION: Across SIOPE, there is a high level of uniformity in fractionation and use of lung shielding. Practices vary regarding other organs-at-risk shielding and implementation of advanced techniques. A SIOPE radiotherapy working group will be established to define international guidelines for pediatric TBI.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid31975481,
title = {Bone sarcomas in the immunotherapy era},
author = {Marie-Françoise Heymann and Kristina Schiavone and Dominique Heymann},
doi = {10.1111/bph.14999},
issn = {1476-5381},
year  = {2021},
date = {2021-01-23},
urldate = {2020-01-23},
journal = {Br J Pharmacol},
volume = {178},
number = {9},
pages = {1955--1972},
abstract = {Bone sarcomas are primary bone tumours found mainly in children and adolescents, as osteosarcoma and Ewing&#039;s sarcoma, and in adults in their 40s as chondrosarcoma. The last four decades the development of therapeutic approaches was based on drug combinations have shown no real improvement in overall survival. Recently oncoimmunology has allowed a better understand of the crucial role played by the immune system in the oncologic process. This led to clinical trials with the aim of reprogramming the immune system to facilitate cancer cell recognition. Immune infiltrates of bone sarcomas have been characterized and their molecular profiling identified as immune therapeutic targets. Unfortunately, the clinical responses in trials remain anecdotal but highlight the necessity to improve the characterization of tumour micro-environment to unlock the immunotherapeutic response, especially in their paediatric forms. Bone sarcomas have entered the immunotherapy era and here we overview the recent developments in immunotherapies in these sarcomas. LINKED ARTICLES: This article is part of a themed issue on The molecular pharmacology of bone and cancer-related bone diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.9/issuetoc.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33478838,
title = {Brachytherapy boost (BT-boost) or stereotactic body radiation therapy boost (SBRT-boost) for high-risk prostate cancer (HR-PCa)},
author = {G Peyraga and T Lizee and J Khalifa and E Blais and G Mauriange-Turpin and S Supiot and S Krhili and P Tremolieres and P Graff-Cailleaud},
doi = {10.1016/j.canrad.2020.11.004},
issn = {1769-6658},
year  = {2021},
date = {2021-01-18},
urldate = {2021-06-01},
journal = {Cancer Radiother},
volume = {25},
number = {4},
pages = {400--409},
abstract = {Systematic review for the treatment of high-risk prostate cancer (HR-PCa, D'Amico classification risk system) with external body radiation therapy (EBRT)+brachytherapy-boost (BT-boost) or with EBRT+stereotactic body RT-boost (SBRT-boost). In March 2020, 391 English citations on PubMed matched with search terms "high risk prostate cancer boost". Respectively 9 and 48 prospective and retrospective studies were on BT-boost and 7 retrospective studies were on SBRT-boost. Two SBRT-boost trials were prospective. Only one study (ASCENDE-RT) directly compared the gold standard treatment [dose-escalation (DE)-EBRT+androgen deprivation treatment (ADT)] versus EBRT+ADT+BT-boost. Biochemical control rates at 9 years were 83% in the experimental arm versus 63% in the standard arm. Cumulative incidence of late grade 3 urinary toxicity in the experimental arm and in the standard arm was respectively 18% and 5%. Two recent studies with HR-PCa (National Cancer Database) demonstrated better overall survival with BT-boost (low dose rate LDR or high dose rate HDR) compared with DE-EBRT. These recent findings demonstrate the superiority of EBRT+BT-boost+ADT versus DE-EBRT+ADT for HR-PCa. It seems that EBRT+BT-boost+ADT could now be considered as a gold standard treatment for HR-PCa. HDR or LDR are options. SBRT-boost represents an attractive alternative, but the absence of randomised trials does not allow us to conclude for HR-PCa. Prospective randomised international phase III trials or meta-analyses could improve the level of evidence of SBRT-boost for HR-PCa.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33461061,
title = {Radical radiotherapy for paediatric solid tumour metastases: An overview of current European protocols and outcomes of a SIOPE multicenter survey},
author = {Sophie C Huijskens and Petra S Kroon and Mark N Gaze and Lorenza Gandola and Stephanie Bolle and Stephane Supiot and Candan D Abakay and Aikaterini Alexopoulou and Jelena Bokun and Marzanna Chojnacka and Alexandre Escande and Jordi Giralt and Semi Harrabi and John H Maduro and Henry Mandeville and Anna Mussano and Aleksandra Napieralska and Laetitia Padovani and Giovanni Scarzello and Beate Timmermann and Line Claude and Enrica Seravalli and Geert O Janssens},
doi = {10.1016/j.ejca.2020.12.004},
issn = {1879-0852},
year  = {2021},
date = {2021-01-16},
urldate = {2021-01-01},
journal = {Eur J Cancer},
volume = {145},
pages = {121--131},
abstract = {PURPOSE/OBJECTIVE: About 20% of children with solid tumours (ST) present with distant metastases (DM). Evidence regarding the use of radical radiotherapy of these DM is sparse and open for personal interpretation. The aim of this survey was to review European protocols and to map current practice regarding the irradiation of DM across SIOPE-affiliated countries.

MATERIALS/METHODS: Radiotherapy guidelines for metastatic sites (bone, brain, distant lymph nodes, lung and liver) in eight European protocols for rhabdomyosarcoma, non-rhabdomyosarcoma soft-tissue sarcoma, Ewing sarcoma, neuroblastoma and renal tumours were reviewed. SIOPE centres irradiating ≥50 children annually were invited to participate in an online survey.

RESULTS: Radiotherapy to at least one metastatic site was recommended in all protocols, except for high-risk neuroblastoma. Per protocol, dose prescription varied per site, and information on delineation and treatment planning/delivery was generally missing. Between July and September 2019, 20/27 centres completed the survey. Around 14% of patients were deemed to have DM from ST at diagnosis, of which half were treated with curative intent. A clear cut-off for a maximum number of DM was not used in half of the centres. Regardless of the tumour type and site, conventional radiotherapy regimens were most commonly used to treat DM. When stereotactic radiotherapy was used, a wide range of fractionation regimens were applied.

CONCLUSION: Current radiotherapy guidelines for DM do not allow a consistent approach in a multicentre setting. Prospective (randomised) trials are needed to define the role of radical irradiation of DM from paediatric ST.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33129591,
title = {Development of prohibitin ligands against osteoporosis},
author = {Redouane Tabti and François Lamoureux and Céline Charrier and Benjamin Ory and Dominique Heymann and Embarek Bentouhami and Laurent Désaubry},
doi = {10.1016/j.ejmech.2020.112961},
issn = {1768-3254},
year  = {2021},
date = {2021-01-15},
urldate = {2021-01-01},
journal = {Eur J Med Chem},
volume = {210},
pages = {112961},
abstract = {Current therapeutic approaches to osteoporosis display some potential adverse effects and a limited efficacy on non-vertebral fracture reduction. Some sulfonylamidines targeting the scaffold proteins prohibitins-1 and 2 (PHB1/2) have been showed to inhibit the formation of osteoclasts in charge of bone resorption. Herein, we report the development of a second generation of anti-osteoclastic PHB ligands. The most potent compound, IN45, showed 88% inhibition at the low concentration of 5 μM, indicates that it might serve as a basis for the development of new antiosteoporotic drugs.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33490021,
title = {The Elderly and the COVID 19 Crisis: A Chronicle of Deaths Foretold, in Isolation and Total Indifference},
author = {Dominique Heymann},
doi = {10.3389/fpubh.2020.602982},
issn = {2296-2565},
year  = {2021},
date = {2021-01-08},
urldate = {2021-01-08},
journal = {Front Public Health},
volume = {8},
pages = {602982},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{D0NR06401G,
title = {Size and ligand effects of gold nanoclusters in alteration of organellar state and translocation of transcription factors in human primary astrocytes},
author = {Evan Rizzel Gran and Franck Bertorelle and Hussein Fakhouri and Rodolphe Antoine and Martina Perić Bakulić and Željka Sanader Maršić and Vlasta Bonačić-Koutecký and Manon Blain and Jack Antel and Dusica Maysinger},
url = {http://dx.doi.org/10.1039/D0NR06401G},
doi = {10.1039/D0NR06401G},
year  = {2021},
date = {2021-01-01},
journal = {Nanoscale},
pages = {-},
publisher = {The Royal Society of Chemistry},
abstract = {Ultra-small gold nanoclusters (AuNCs) with designed sizes and ligands are gaining popularity for biomedical purposes and ultimately for human imaging and therapeutic applications. Human non-tumor brain cells, astrocytes, are of particular interest because they are abundant and play a role in functional regulation of neurons under physiological and pathological conditions. Human primary astrocytes were treated with AuNCs of varying sizes (Au10, Au15, Au18, Au25) and ligand composition (glutathione, polyethylene glycol, N-acetyl cysteine). Concentration and time-dependent studies showed no significant cell loss with AuNC concentrations &lt;10 μM. AuNC treatment caused marked differential astrocytic responses at the organellar and transcription factor level. The effects were exacerbated under severe oxidative stress induced by menadione. Size-dependent effects were most remarkable with the smallest and largest AuNCs (10, 15 Au atoms versus 25 Au atoms) and might be related to the accessibility of biological targets toward the AuNC core, as demonstrated by QM/MM simulations. In summary, these findings suggest that AuNCs are not inert in primary human astrocytes, and that their sizes play a critical role in modulation of organellar and redox-responsive transcription factor homeostasis.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Hoguin2021,
title = {Genome ‑ wide analysis of allele ‑ specific expression of genes in the model diatom Phaeodactylum tricornutum},
author = {Antoine Hoguin and Achal Rastogi and Chris Bowler and Leila Tirichine},
url = {https://doi.org/10.1038/s41598-021-82529-1},
doi = {10.1038/s41598-021-82529-1},
issn = {2045-2322},
year  = {2021},
date = {2021-01-01},
journal = {Scientific Reports},
pages = {1--10},
publisher = {Nature Publishing Group UK},
abstract = {Recent advances in next generation sequencing technologies have allowed the discovery of widespread autosomal allele-specific expression (aASE) in mammals and plants with potential phenotypic effects. Extensive numbers of genes with allele-specific expression have been described in the diatom Fragilariopsis cylindrus in association with adaptation to external cues, as well as in Fistulifera solaris in the context of natural hybridization. However, the role of aASE and its extent in diatoms remain elusive. In this study, we investigate allele-specific expression in the model diatom Phaeodactylum tricornutum by the re-analysis of previously published whole genome RNA sequencing data and polymorphism calling. We found that 22% of P. tricornutum genes show moderate bias in allelic expression while 1% show nearly complete monoallelic expression. Biallelic expression associates with genes encoding components of protein metabolism while moderately biased genes associate with functions in catabolism and protein transport. We validated candidate genes by pyrosequencing and found that moderate biases in allelic expression were less stable than monoallelically expressed genes that showed consistent bias upon experimental validations at the population level and in subcloning experiments. Our approach provides the basis for the analysis of aASE in P. tricornutum and could be routinely implemented to test for variations in allele expression under different environmental conditions.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{https://doi.org/10.1002/chem.202004672,
title = {Polyvalent Transition-State Analogues of Sialyl Substrates Strongly Inhibit Bacterial Sialidases**},
author = {Coralie Assailly and Clarisse Bridot and Amélie Saumonneau and Paul Lottin and Benoit Roubinet and Eva-Maria Krammer and Francesca François and Federica Vena and Ludovic Landemarre and Dimitri Alvarez Dorta and David Deniaud and Cyrille Grandjean and Charles Tellier and Sagrario Pascual and Véronique Montembault and Laurent Fontaine and Franck Daligault and Julie Bouckaert and Sébastien G Gouin},
url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202004672},
doi = {https://doi.org/10.1002/chem.202004672},
year  = {2021},
date = {2021-01-01},
journal = {Chemistry – A European Journal},
volume = {27},
number = {9},
pages = {3142-3150},
abstract = {Abstract Bacterial sialidases (SA) are validated drug targets expressed by common human pathogens such as Streptococcus pneumoniae, Vibrio cholerae, or Clostridium perfringens. Noncovalent inhibitors of bacterial SA capable of reaching the submicromolar level are rarely reported. In this work, multi- and polyvalent compounds are developed, based on the transition-state analogue 2-deoxy-2,3-didehydro-N-acetylneuraminic (DANA). Poly-DANA inhibits the catalytic activity of SA from S. pneumoniae (NanA) and the symbiotic microorganism B. thetaiotaomicron (BtSA) at the picomolar and low nanomolar levels (expressed in moles of molecules and of DANA, respectively). Each DANA grafted to the polymer surpasses the inhibitory potential of the monovalent analogue by more than four orders of magnitude, which represents the highest multivalent effect reported so far for an enzyme inhibition. The synergistic interaction is shown to operate exclusively in the catalytic domain, and not in the flanked carbohydrate-binding module (CBM). These results offer interesting perspectives for the multivalent inhibition of other SA families lacking a CBM, such as viral, parasitic, or human SA.},
keywords = {d-zyme, enzymes, équipe 2, inhibitors, Multivalency, sialidases, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{ogondacharacterization,
title = {Characterization and engineering of two new GH9 and GH48 cellulases from a Bacillus pumilus isolated from Lake Bogoria},
author = {Lydia A Ogonda and Amélie Saumonneau and Michel Dion and Edward K Muge and Benson M Wamalwa and Francis J Mulaa and Charles Tellier},
doi = {10.1007/s10529-020-03056-z},
year  = {2021},
date = {2021-01-01},
journal = {Biotechnology Letters},
volume = {43},
pages = {691–700},
publisher = {Springer},
abstract = {Objectives. To search for new alkaliphilic cellulases and to improve their efficiency on crystalline cellulose through molecular engineering 
Results. Two novel cellulases, BpGH9 and BpGH48, from a Bacillus pumilus strain were identified, cloned and biochemically characterized. BpGH9 is a modular endocellulase belonging to the glycoside hydrolase 9 family (GH9), which contains a catalytic module (GH) and a carbohydrate-binding module belonging to class 3 and subclass c (CBM3c). This enzyme is extremely tolerant to high alkali pH and remains significantly active at pH 10. BpGH48 is an exocellulase, belonging to the glycoside hydrolase 48 family (GH48) and acts on the reducing end of oligo-β1,4 glucanes. A truncated form of BpGH9 and a chimeric fusion with an additional CBM3a module was constructed. The deletion of the CBM3c module results in a significant decline in the catalytic activity. However, fusion of CBM3a, although in a non native position, enhanced the activity of BpGH9 on crystalline cellulose. 
 Conclusions. A new alkaliphilic endocellulase BpGH9, was cloned and engineered as a fusion protein (CBM3a-BpGH9), which led to an improved activity on crystalline cellulose.},
keywords = {d-zyme, team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{molecules26092759,
title = {Lipase-Catalyzed Production of Sorbitol Laurate in a “2-in-1” Deep Eutectic System: Factors Affecting the Synthesis and Scalability},
author = {André Delavault and Oleksandra Opochenska and Laura Laneque and Hannah Soergel and Claudia Muhle-Goll and Katrin Ochsenreither and Christoph Syldatk},
url = {https://www.mdpi.com/1420-3049/26/9/2759},
doi = {10.3390/molecules26092759},
issn = {1420-3049},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Molecules},
volume = {26},
number = {9},
abstract = {Surfactants, such as glycolipids, are specialty compounds that can be encountered daily in cleaning agents, pharmaceuticals or even in food. Due to their wide range of applications and, more notably, their presence in hygiene products, the demand is continuously increasing worldwide. The established chemical synthesis of glycolipids presents several disadvantages, such as lack of specificity and selectivity. Moreover, the solubility of polyols, such as sugars or sugar alcohols, in organic solvents is rather low. The enzymatic synthesis of these compounds is, however, possible in nearly water-free media using inexpensive and renewable building blocks. Using lipases, ester formation can be achieved under mild conditions. We propose, herein, a “2-in-1” system that overcomes solubility problems, as a Deep Eutectic System (DES) made of sorbitol and choline chloride replaces either a purely organic or aqueous medium. For the first time, 16 commercially available lipase formulations were compared, and the factors affecting the conversion were investigated to optimize this process, owing to a newly developed High-Performance Liquid Chromatography-Evaporative Light Scattering Detector (HPLC-ELSD) method for quantification. Thus, using 50 g/L of lipase formulation Novozym 435® at 50 °C, the optimized synthesis of sorbitol laurate (SL) allowed to achieve 28% molar conversion of 0.5 M of vinyl laurate to its sugar alcohol monoester when the DES contained 5 wt.% water. After 48h, the de novo synthesized glycolipid was separated from the media by liquid–liquid extraction, purified by flash-chromatography and characterized thoroughly by one- and two-dimensional Nuclear Magnetic Resonance (NMR) experiments combined to Mass Spectrometry (MS). In completion, we provide initial proof of scalability for this process. Using a 2.5 L stirred tank reactor (STR) allowed a batch production reaching 25 g/L in a highly viscous two-phase system.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{ijms22031113,
title = {Replication-Coupled Chromatin Remodeling: An Overview of Disassembly and Assembly of Chromatin during Replication},
author = {Céline Duc and Christophe Thiriet},
url = {https://www.mdpi.com/1422-0067/22/3/1113
hal-04210949v1 },
doi = {10.3390/ijms22031113},
issn = {1422-0067},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {International Journal of Molecular Sciences},
volume = {22},
number = {3},
abstract = {The doubling of genomic DNA during the S-phase of the cell cycle involves the global remodeling of chromatin at replication forks. The present review focuses on the eviction of nucleosomes in front of the replication forks to facilitate the passage of replication machinery and the mechanism of replication-coupled chromatin assembly behind the replication forks. The recycling of parental histones as well as the nuclear import and the assembly of newly synthesized histones are also discussed with regard to the epigenetic inheritance.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{rahmani_implication_2021,
title = {Implication of the Type IV Secretion System in the Pathogenicity of Vibrio tapetis, the Etiological Agent of Brown Ring Disease Affecting the Manila Clam Ruditapes philippinarum},
author = {Alexandra Rahmani and François Delavat and Christophe Lambert and Nelly Le Goic and Eric Dabas and Christine Paillard and Vianney Pichereau},
url = {https://www.frontiersin.org/articles/10.3389/fcimb.2021.634427/full},
doi = {10.3389/fcimb.2021.634427},
issn = {2235-2988},
year  = {2021},
date = {2021-01-01},
urldate = {2021-04-29},
journal = {Frontiers in Cellular and Infection Microbiology},
volume = {11},
pages = {634427},
abstract = {Vibrio tapetis is a Gram-negative bacterium that causes infections of mollusk bivalves and ﬁsh. The Brown Ring Disease (BRD) is an infection caused by V. tapetis that primarily affects the Manila clam Ruditapes philippinarum. Recent studies have shown that a type IV secretion system (T4SS) gene cluster is exclusively found in strains of V. tapetis pathogenic to clams. However, whether the T4SS is implicated or not during the infection process remains unknown. The aim of this study was to create and characterize a V. tapetis T4SS null mutant, obtained by a near-complete deletion of the virB4 gene, in order to determine the role of T4SS in the development of BRD. This study demonstrated that the T4SS is neither responsible for the loss of hemocyte adhesion capacities, nor for the decrease of the lysosomal activity during BRD. Nevertheless, we observed a 50% decrease of the BRD prevalence and a decrease of mortality dynamics with the DvirB4 mutant. This work demonstrates that the T4SS of V. tapetis plays an important role in the development of BRD in the Manila clam.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{lapaillerie_silico_2021,
title = {In Silico, In Vitro and In Cellulo Models for Monitoring SARS-CoV-2 Spike/Human ACE2 Complex, Viral Entry and Cell Fusion},
author = {Delphine Lapaillerie and Cathy Charlier and Henrique S Fernandes and Sergio F Sousa and Paul Lesbats and Pierre Weigel and Alexandre Favereaux and Véronique Guyonnet-Duperat and Vincent Parissi},
url = {https://www.mdpi.com/1999-4915/13/3/365},
doi = {10.3390/v13030365},
issn = {1999-4915},
year  = {2021},
date = {2021-01-01},
urldate = {2021-04-30},
journal = {Viruses},
volume = {13},
number = {3},
pages = {365},
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent responsible for the recent coronavirus disease 2019 (COVID-19) pandemic. Productive SARS-CoV-2 infection relies on viral entry into cells expressing angiotensin-converting enzyme 2 (ACE2). Indeed, viral entry into cells is mostly mediated by the early interaction between the viral spike protein S and its ACE2 receptor. The S/ACE2 complex is, thus, the ﬁrst contact point between the incoming virus and its cellular target; consequently, it has been considered an attractive therapeutic target. To further characterize this interaction and the cellular processes engaged in the entry step of the virus, we set up various in silico, in vitro and in cellulo approaches that allowed us to speciﬁcally monitor the S/ACE2 association. We report here a computational model of the SARS-CoV-2 S/ACE2 complex, as well as its biochemical and biophysical monitoring using pulldown, AlphaLISA and biolayer interferometry (BLI) binding assays. This led us to determine the kinetic parameters of the S/ACE2 association and dissociation steps. In parallel to these in vitro approaches, we developed in cellulo transduction assays using SARS-CoV-2 pseudotyped lentiviral vectors and HEK293T-ACE2 cell lines generated in-house. This allowed us to recapitulate the early replication stage of the infection mediated by the S/ACE2 interaction and to detect cell fusion induced by the interaction. Finally, a cell imaging system was set up to directly monitor the S/ACE2 interaction in a cellular context and a ﬂow cytometry assay was developed to quantify this association at the cell surface. Together, these different approaches are available for both basic and clinical research, aiming to characterize the entry step of the original SARS-CoV-2 strain and its variants as well as to investigate the possible chemical modulation of this interaction. All these models will help in identifying new antiviral agents and new chemical tools for dissecting the virus entry step.},
keywords = {impact},
pubstate = {published},
tppubtype = {article}
}
@article{FLOCH2021,
title = {A Review of the Literature Organized Into a New Database: RHeference},
author = {Aline Floch and Stéphane Téletchéa and Christophe Tournamille and Alexandre G de Brevern and France Pirenne},
url = {https://www.sciencedirect.com/science/article/pii/S0887796321000109},
doi = {https://doi.org/10.1016/j.tmrv.2021.04.002},
issn = {0887-7963},
year  = {2021},
date = {2021-01-01},
journal = {Transfusion Medicine Reviews},
abstract = {Hundreds of articles containing heterogeneous data describe D variants or add to the knowledge of known alleles. Data can be difficult to find despite existing online blood group resources and genetic and literature databases. We have developed a modern, elaborate database for D variants, thanks to an extensive literature search with meticulous curation of 387 peer-reviewed articles and 80 abstracts from major conferences and other sources. RHeference contains entries for 710 RHD alleles, 11 RHCE alleles, 30 phenotype descriptions (preventing data loss from historical sources), 35 partly characterized alleles, 3 haplotypes, and 16 miscellaneous entries. The entries include molecular, phenotypic, serological, alloimmunization, haplotype, geographical, and other data, detailed for each source. The main characteristics are summarized for each entry. The sources for all information are included and easily accessible through doi and PMID links. Overall, the database contains more than 10,000 individual pieces of data. We have set up the database architecture based on our previous expertise on database setup and biocuration for other topics, using modern technologies such as the Django framework, BioPython, Bootstrap, and Jquery. This architecture allows an easy access to data and enables simple and complex queries: combining multiple mutations, keywords, or any of the characteristics included in the database. RHeference provides a complement to existing resources and will continue to grow as our knowledge expands and new articles are published. The database url is http://www.rheference.org/.},
keywords = {Database, Immunogenetics, RH blood group, RHD gene, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{prasanna_use_2021,
title = {On the use of adenovirus dodecahedron as a carrier for glycoconjugate vaccines},
author = {Maruthi Prasanna and Malgorzata Podsiadla-Bialoskorska and Damian Mielecki and Nicolas Ruffier and Amina Fateh and Annie Lambert and Mathieu Fanuel and Emilie Camberlein and Ewa Szolajska and Cyrille Grandjean},
url = {https://doi.org/10.1007/s10719-021-09999-3},
doi = {10.1007/s10719-021-09999-3},
issn = {1573-4986},
year  = {2021},
date = {2021-01-01},
urldate = {2021-06-16},
journal = {Glycoconjugate Journal},
abstract = {Virus-Like Particles (VLPs) have been used as immunogenic molecules in numerous recombinant vaccines. VLPs can also serve as vaccine platform to exogenous antigens, usually peptides incorporated within the protein sequences which compose the VLPs or conjugated to them. We herein described the conjugation of a synthetic tetrasaccharide mimicking the Streptococcus pneumoniae serotype 14 capsular polysaccharide to recombinant adenoviral type 3 dodecahedron, formed by the self-assembling of twelve penton bases and investigated the induced immune response when administered subcutaneously (s.c.). Whether formulated in the form of a dodecahedron or disassembled, the glycoconjugate induced an anti-protein response after two and three immunizations equivalent to that observed when the native dodecahedron was administered. On the other hand, the glycoconjugate induced a weak anti-IgM response which diminishes after two doses but no IgM-to-IgG switch was observed in mice against the serotype 14 capsular polysaccharide. In definitive, the whole conjugation process preserved both particulate nature and immunogenicity of the adenoviral dodecahedron. Further studies are needed to fully exploit adenoviral dodecahedron potential in terms of plasticity towards sequence engineering and of its capacity to stimulate the immune system via the intranasal route of administration as well as to shift the response to the carbohydrate antigen by playing both with the carbohydrate to protein ratio and the length of the synthetic carbohydrate antigen.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{gheyouche_structural_2021,
title = {Structural Design and Analysis of the RHOA-ARHGEF1 Binding Mode: Challenges and Applications for Protein-Protein Interface Prediction},
author = {Ennys Gheyouche and Matthias Bagueneau and Gervaise Loirand and Bernard Offmann and Stéphane Téletchéa},
doi = {10.3389/fmolb.2021.643728},
issn = {2296-889X},
year  = {2021},
date = {2021-01-01},
journal = {Frontiers in Molecular Biosciences},
volume = {8},
pages = {643728},
abstract = {The interaction between two proteins may involve local movements, such as small side-chains re-positioning or more global allosteric movements, such as domain rearrangement. We studied how one can build a precise and detailed protein-protein interface using existing protein-protein docking methods, and how it can be possible to enhance the initial structures using molecular dynamics simulations and data-driven human inspection. We present how this strategy was applied to the modeling of RHOA-ARHGEF1 interaction using similar complexes of RHOA bound to other members of the Rho guanine nucleotide exchange factor family for comparative assessment. In parallel, a more crude approach based on structural superimposition and molecular replacement was also assessed. Both models were then successfully refined using molecular dynamics simulations leading to protein structures where the major data from scientific literature could be recovered. We expect that the detailed strategy used in this work will prove useful for other protein-protein interface design. The RHOA-ARHGEF1 interface modeled here will be extremely useful for the design of inhibitors targeting this protein-protein interaction (PPI).},
keywords = {ARHGEF1, molecular dynamics simulation, PPI, protein-protein docking, RHOA, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{10.1093/nargab/lqab107,
title = {Identification and characterization of histones in Physarum polycephalum evidence a phylogenetic vicinity of Mycetozoans to the animal kingdom},
author = {Axel Poulet and Laxmi Narayan Mishra and Stéphane Téletchéa and Jeffrey J Hayes and Yannick Jacob and Christophe Thiriet and Céline Duc},
url = {https://doi.org/10.1093/nargab/lqab107
hal-03595485v1 },
doi = {10.1093/nargab/lqab107},
issn = {2631-9268},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {NAR Genomics and Bioinformatics},
volume = {3},
number = {4},
abstract = {Physarum polycephalum belongs to Mycetozoans, a phylogenetic clade apart from the animal, plant and fungus kingdoms. Histones are nuclear proteins involved in genome organization and regulation and are among the most evolutionary conserved proteins within eukaryotes. Therefore, this raises the question of their conservation in Physarum and the position of this organism within the eukaryotic phylogenic tree based on histone sequences. We carried out a comprehensive study of histones in Physarum polycephalum using genomic, transcriptomic and molecular data. Our results allowed to identify the different isoforms of the core histones H2A, H2B, H3 and H4 which exhibit strong conservation of amino acid residues previously identified as subject to post-translational modifications. Furthermore, we also identified the linker histone H1, the most divergent histone, and characterized a large number of its PTMs by mass spectrometry. We also performed an in-depth investigation of histone genes and transcript structures. Histone proteins are highly conserved in Physarum and their characterization will contribute to a better understanding of the polyphyletic Mycetozoan group. Our data reinforce that P. polycephalum is evolutionary closer to animals than plants and located at the crown of the eukaryotic tree. Our study provides new insights in the evolutionary history of Physarum and eukaryote lineages.},
note = {lqab107},
keywords = {team 1, team 5},
pubstate = {published},
tppubtype = {article}
}
@article{RN8,
title = {Molecular actors of seed germination and haustoriogenesis in parasitic weeds},
author = {Guillaume Brun and Thomas Spallek and Philippe Simier and Philippe Delavault},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133557/pdf/kiaa041.pdf},
doi = {10.1093/plphys/kiaa041},
issn = {0032-0889 (Print) 0032-0889},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Plant Physiol},
volume = {185},
number = {4},
pages = {1270-1281},
abstract = {One-sentence summary Recent advances provide insight into the molecular mechanisms underlying host-dependent seed germination and haustorium formation in parasitic plants.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{RN13,
title = {A Phelipanche ramosa KAI2 protein perceives strigolactones and isothiocyanates enzymatically},
author = {Alexandre Saint Germain and Anse Jacobs and Guillaume Brun and Jean-Bernard Pouvreau and Lukas Braem and David Cornu and Guillaume Clavé and Emmanuelle Baudu and Vincent Steinmetz and Vincent Servajean and Susann Wicke and Kris Gevaert and Philippe Simier and Sophie Goormachtig and Philippe Delavault and François-Didier Boyer},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553955/pdf/main.pdf},
doi = {10.1016/j.xplc.2021.100166},
issn = {2590-3462},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Plant Commun},
volume = {2},
number = {5},
pages = {100166},
abstract = {Phelipanche ramosa is an obligate root-parasitic weed that threatens major crops in central Europe. In order to germinate, it must perceive various structurally divergent host-exuded signals, including isothiocyanates (ITCs) and strigolactones (SLs). However, the receptors involved are still uncharacterized. Here, we identify five putative SL receptors in P. ramosa and show that PrKAI2d3 is involved in the stimulation of seed germination. We demonstrate the high plasticity of PrKAI2d3, which allows it to interact with different chemicals, including ITCs. The SL perception mechanism of PrKAI2d3 is similar to that of endogenous SLs in non-parasitic plants. We provide evidence that PrKAI2d3 enzymatic activity confers hypersensitivity to SLs. Additionally, we demonstrate that methylbutenolide-OH binds PrKAI2d3 and stimulates P. ramosa germination with bioactivity comparable to that of ITCs. This study demonstrates that P. ramosa has extended its signal perception system during evolution, a fact that should be considered for the development of specific and efficient biocontrol methods.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{RN27,
title = {The Physcomitrium (Physcomitrella) patens PpKAI2L receptors for strigolactones and related compounds function via MAX2-dependent and -independent pathways},
author = {Mauricio Lopez-Obando and Ambre Guillory and François-Didier Boyer and David Cornu and Beate Hoffmann and Philippe Le Bris and Jean-Bernard Pouvreau and Philippe Delavault and Catherine Rameau and Alexandre Saint Germain and Sandrine Bonhomme},
url = {https://academic.oup.com/plcell/article-abstract/33/11/3487/6359828?redirectedFrom=fulltext},
doi = {10.1093/plcell/koab217},
issn = {1040-4651 (Print) 1040-4651},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Plant Cell},
volume = {33},
number = {11},
pages = {3487-3512},
abstract = {In angiosperms, the α/β hydrolase DWARF14 (D14), along with the F-box protein MORE AXILLARY GROWTH2 (MAX2), perceives strigolactones (SL) to regulate developmental processes. The key SL biosynthetic enzyme CAROTENOID CLEAVAGE DIOXYGENASE8 (CCD8) is present in the moss Physcomitrium patens, and PpCCD8-derived compounds regulate moss extension. The PpMAX2 homolog is not involved in the SL response, but 13 PpKAI2LIKE (PpKAI2L) genes homologous to the D14 ancestral paralog KARRIKIN INSENSITIVE2 (KAI2) encode candidate SL receptors. In Arabidopsis thaliana, AtKAI2 perceives karrikins and the elusive endogenous KAI2-Ligand (KL). Here, germination assays of the parasitic plant Phelipanche ramosa suggested that PpCCD8-derived compounds are likely noncanonical SLs. (+)-GR24 SL analog is a good mimic for PpCCD8-derived compounds in P. patens, while the effects of its enantiomer (-)-GR24, a KL mimic in angiosperms, are minimal. Interaction and binding assays of seven PpKAI2L proteins pointed to the stereoselectivity toward (-)-GR24 for a single clade of PpKAI2L (eu-KAI2). Enzyme assays highlighted the peculiar behavior of PpKAI2L-H. Phenotypic characterization of Ppkai2l mutants showed that eu-KAI2 genes are not involved in the perception of PpCCD8-derived compounds but act in a PpMAX2-dependent pathway. In contrast, mutations in PpKAI2L-G, and -J genes abolished the response to the (+)-GR24 enantiomer, suggesting that PpKAI2L-G, and -J proteins are receptors for moss SLs.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34028679b,
title = {Strigolactone-Like Bioactivity via Parasitic Plant Germination Bioassay},
author = {Jean-Bernard Pouvreau and Lucie Poulin and Sarah Huet and Philippe Delavault},
doi = {10.1007/978-1-0716-1429-7_6},
issn = {1940-6029},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Methods Mol Biol},
volume = {2309},
pages = {59--73},
abstract = {Strigolactones are a class of plant hormones involved in shoot branching, growth of symbiotic arbuscular mycorrhizal fungi, and germination of parasitic plant seeds. Assaying new molecules or compound exhibiting strigolactone-like activities is therefore important but unfortunately time-consuming and hard to implement because of the extremely low concentrations at which they are active. Seeds of parasite plants are natural integrator of these hormones since they can perceive molecule concentrations in the picomolar to nanomolar range stimulating their germination. Here we describe a simple and inexpensive method to evaluate the activity of these molecules by scoring the germination of parasitic plant seeds upon treatment with these molecules. Up to four molecules can be assayed from a single 96-well plate by this method. A comparison of SL-like bioactivities between molecules is done by determining the EC50 and the maximum percentage of germination.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34517085,
title = {The intratumoral microbiome: Characterization methods and functional impact},
author = {Clément J F Heymann and Jean-Marie Bard and Marie-Françoise Heymann and Dominique Heymann and Christine Bobin-Dubigeon},
doi = {10.1016/j.canlet.2021.09.009},
issn = {1872-7980},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Cancer Lett},
volume = {522},
pages = {63--79},
abstract = {Live-pathogenic bacteria, which were identified inside tumors hundreds year ago, are key elements in modern cancer research. As they have a relatively accessible genome, they offer a multitude of metabolic engineering opportunities, useful in several clinical fields. Better understanding of the tumor microenvironment and its associated microbiome would help conceptualize new metabolically engineered species, triggering efficient therapeutic responses against cancer. Unfortunately, given the low microbial biomass nature of tumors, characterizing the tumor microbiome remains a challenge. Tumors have a high host versus bacterial DNA ratio, making it extremely complex to identify tumor-associated bacteria. Nevertheless, with the improvements in next-generation analytic tools, recent studies demonstrated the existence of intratumor bacteria inside defined tumors. It is now proven that each cancer subtype has a unique microbiome, characterized by bacterial communities with specific metabolic functions. This review provides a brief overview of the main approaches used to characterize the tumor microbiome, and of the recently proposed functions of intracellular bacteria identified in oncological entities. The therapeutic aspects of live-pathogenic microbes are also discussed, regarding the tumor microenvironment of each cancer type.},
keywords = {Microbial diversity, microbiome, out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33408768,
title = {The twin cytokines interleukin-34 and CSF-1: masterful conductors of macrophage homeostasis},
author = {Javier Muñoz-Garcia and Denis Cochonneau and Stéphane Télétchéa and Emilie Moranton and Didier Lanoe and Régis Brion and Frédéric Lézot and Marie-Françoise Heymann and Dominique Heymann},
doi = {10.7150/thno.50683},
issn = {1838-7640},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Theranostics},
volume = {11},
number = {4},
pages = {1568--1593},
abstract = {Macrophages are specialized cells that control tissue homeostasis. They include non-resident and tissue-resident macrophage populations which are characterized by the expression of particular cell surface markers and the secretion of molecules with a wide range of biological functions. The differentiation and polarization of macrophages relies on specific growth factors and their receptors. Macrophage-colony stimulating factor (CSF-1) and interleukine-34 (IL-34), also known as "twin" cytokines, are part of this regluatory landscape. CSF-1 and IL-34 share a common receptor, the macrophage-colony stimulating factor receptor (CSF-1R), which is activated in a similar way by both factors and turns on identical signaling pathways. However, there is some discrete differential activation leading to specific activities. In this review, we disscuss recent progress in understanding of the role of the twin cytokines in macrophage differentiation, from their interaction with CSF-1R and the activation of signaling pathways, to their implication in macrophage polarization of non-resident and tissue-resident macrophages. A special focus on IL-34, its involvement in pathophsyiological contexts, and its potential as a theranostic target for macrophage therapy will be proposed.},
keywords = {team 1, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Zhao2020b,
title = {Genome wide natural variation of H3K27me3 selectively marks genes predicted to be important for cell differentiation in Phaeodactylum tricornutum},
author = {Xue Zhao and Achal Rastogi and Anne Flore {Deton Cabanillas} and Ouardia {Ait Mohamed} and Catherine Cantrel and Berangère Lombard and Omer Murik and Auguste Genovesio and Chris Bowler and Daniel Bouyer and Damarys Loew and Xin Lin and Alaguraj Veluchamy and Fabio Rocha Jimenez Vieira and Leila Tirichine},
url = {https://onlinelibrary.wiley.com/doi/10.1111/nph.17129},
doi = {10.1111/nph.17129},
issn = {0028-646X},
year  = {2021},
date = {2021-01-01},
urldate = {2020-12-01},
journal = {New Phytologist},
pages = {nph.17129},
publisher = {Blackwell Publishing Ltd},
abstract = {In multicellular organisms, Polycomb Repressive Complex2 (PRC2) is known to deposit tri-methylation of lysine 27 of histone H3 (H3K27me3) to establish and maintain gene silencing, critical for developmentally regulated processes. The PRC2 complex is absent in both widely studied model yeasts, which initially suggested that PRC2 arose with the emergence of multicellularity. However, its discovery in several unicellular species including microalgae questions its role in unicellular eukaryotes. Here, we use Phaeodactylum tricornutum enhancer of zeste E(z) knockouts and show that P. tricornutum E(z) is responsible for di- and tri-methylation of lysine 27 of histone H3. H3K27me3 depletion abolishes cell morphology in P. tricornutum providing evidence for its role in cell differentiation. Genome-wide profiling of H3K27me3 in fusiform and triradiate cells further revealed genes that may specify cell identity. These results suggest a role for PRC2 and its associated mark in cell differentiation in unicellular species, and highlight their ancestral function in a broader evolutionary context than currently is appreciated.},
keywords = {cell differentiation, H3K27me3, microalgae, Phaeodactylum tricornutum, polycomb, team 5, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34595122,
title = {Interaction Between Modern Radiotherapy and Immunotherapy for Metastatic Prostate Cancer},
author = {Luc Ollivier and Maureen Labbé and Delphine Fradin and Vincent Potiron and Stéphane Supiot},
doi = {10.3389/fonc.2021.744679},
issn = {2234-943X},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Front Oncol},
volume = {11},
pages = {744679},
abstract = {Prostate cancer is the most frequently diagnosed cancer in men and a leading cause of cancer-related death. In recent decades, the development of immunotherapies has resulted in great promise to cure metastatic disease. However, prostate cancer has failed to show any significant response, presumably due to its immunosuppressive microenvironment. There is therefore growing interest in combining immunotherapy with other therapies able to relieve the immunosuppressive microenvironment. Radiation therapy remains the mainstay treatment for prostate cancer patients, is known to exhibit immunomodulatory effects, depending on the dose, and is a potent inducer of immunogenic tumor cell death. Optimal doses of radiotherapy are thus expected to unleash the full potential of immunotherapy, improving primary target destruction with further hope of inducing immune-cell-mediated elimination of metastases at distance from the irradiated site. In this review, we summarize the current knowledge on both the tumor immune microenvironment in prostate cancer and the effects of radiotherapy on it, as well as on the use of immunotherapy. In addition, we discuss the utility to combine immunotherapy and radiotherapy to treat oligometastatic metastatic prostate cancer.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34118357,
title = {Recommendations for planning and delivery of radical radiotherapy for localized urothelial carcinoma of the bladder},
author = {Jonathan Khalifa and Stéphane Supiot and Géraldine Pignot and Christophe Hennequin and Pierre Blanchard and David Pasquier and Nicolas Magné and Renaud de Crevoisier and Pierre Graff-Cailleaud and Olivier Riou and Morgane Cabaillé and David Azria and Igor Latorzeff and Gilles Créhange and Olivier Chapet and Morgan Rouprêt and Sarah Belhomme and Arnaud Mejean and Stéphane Culine and Paul Sargos},
doi = {10.1016/j.radonc.2021.06.011},
issn = {1879-0887},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Radiother Oncol},
volume = {161},
pages = {95--114},
abstract = {PURPOSE: Curative radio-chemotherapy is recognized as a standard treatment option for muscle-invasive bladder cancer (MIBC). Nevertheless, the technical aspects for MIBC radiotherapy are heterogeneous with a lack of practical recommendations.

METHODS AND MATERIALS: In 2018, a workshop identified the need for two cooperative groups to develop consistent, evidence-based guidelines for irradiation technique in the delivery of curative radiotherapy. Two radiation oncologists performed a review of the literature addressing several topics relative to radical bladder radiotherapy: planning computed tomography acquisition, target volume delineation, radiation schedules (total dose and fractionation) and dose delivery (including radiotherapy techniques, image-guided radiotherapy (IGRT) and adaptive treatment modalities). Searches for original and review articles in the PubMed and Google Scholar databases were conducted from January 1990 until March 2020. During a meeting conducted in October 2020, results on 32 topics were presented and discussed with a working group involving 15 radiation oncologists, 3 urologists and one medical oncologist. We applied the American Urological Association guideline development's method to define a consensus strategy.

RESULTS: A consensus was obtained for all 34 except 4 items. The group did not obtain an agreement on CT enhancement added value for planning, PTV margins definition for empty bladder and full bladder protocols, and for pelvic lymph-nodes irradiation. High quality evidence was shown in 6 items; 8 items were considered as low quality of evidence.

CONCLUSION: The current recommendations propose a homogenized modality of treatment both for routine clinical practice and for future clinical trials, following the best evidence to date, analyzed with a robust methodology. The XXX group formulates practical guidelines for the implementation of innovative techniques such as adaptive radiotherapy.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34016489,
title = {Discontinuous stereotactic body radiotherapy schedule increases overall survival in early-stage non-small cell lung cancer},
author = {L Duvergé and P-Y Bondiau and L Claude and S Supiot and L Vaugier and F Thillays and J Doyen and C Ricordel and H Léna and J Bellec and E Chajon and R de Crevoisier and J Castelli},
doi = {10.1016/j.lungcan.2021.05.016},
issn = {1872-8332},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Lung Cancer},
volume = {157},
pages = {100--108},
abstract = {OBJECTIVES: The duration of stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) may affect patient outcomes. We aimed to determine the impact of a continuous versus discontinuous SBRT schedule on local control (LC) and overall survival (OS) in NSCLC patients.

MATERIALS AND METHODS: Consecutive NSCLC stage I patients (475) treated with SBRT in four centers were retrospectively analyzed. The delivered dose ranged from 48 to 75 Gy in 3-10 fractions. Based on the ratio between the treatment duration (TD) and number of fractions (n), patients were divided into two groups: continuous schedule (CS) (TD ≤ 1.6n; 239 patients) and discontinuous schedule (DS) (TD &gt; 1.6n; 236 patients). LC and OS were compared using Cox regression analyses after propensity score matching (216 pairs).

RESULTS: The median follow-up period was 41 months. Multivariate analysis showed that the DS (hazard ratio (HR): 0.42; 95 % confidence interval (CI): 0.22-0.78) and number of fractions (HR: 1.24; 95 % CI: 1.07-1.43) were significantly associated with LC. The DS (HR: 0.67; 95 % CI: 0.51-0.89), age (HR: 1.02; 95 % CI: 1-1.03), WHO performance status (HR: 2.27; 95 % CI: 1.39-3.7), and T stage (HR: 1.4; 95 % CI: 1.03-1.87) were significantly associated with OS. The 3-year LC and OS were 92 % and 64 % and 81 % and 53 % for DS and CS treatments, respectively (p &lt; 0.01). Cox analysis confirmed that the discontinuous SBRT schedule significantly increased LC and OS.

CONCLUSION: DS is associated with significantly improved LC and OS in early-stage NSCLC patients treated with SBRT.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33358745,
title = {[Stereotactic radiotherapy in urologic cancers: Reports from the 3rd international meeting of the Groupe Francophone de Radiothérapie Urologique (GFRU)]},
author = {Tanguy Perennec and Stéphane Supiot},
doi = {10.1016/j.bulcan.2020.10.015},
issn = {1769-6917},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Bull Cancer},
volume = {108},
number = {1},
pages = {125--128},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33303195,
title = {[Innovation in radiotherapy in 2021]},
author = {Ingrid Masson and Marie Dutreix and Stéphane Supiot},
doi = {10.1016/j.bulcan.2020.10.005},
issn = {1769-6917},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Bull Cancer},
volume = {108},
number = {1},
pages = {42--49},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid34247896,
title = {OLIGOPELVIS GETUG P07, a Multicenter Phase II Trial of Combined High-dose Salvage Radiotherapy and Hormone Therapy in Oligorecurrent Pelvic Node Relapses in Prostate Cancer},
author = {Stéphane Supiot and Loig Vaugier and David Pasquier and Xavier Buthaud and Nicolas Magné and Didier Peiffert and Paul Sargos and Gilles Crehange and Pascal Pommier and Genevieve Loos and Ali Hasbini and Igor Latorzeff and Marlon Silva and Fabrice Denis and Jean-Léon Lagrange and Cyrille Morvan and Loic Campion and Audrey Blanc-Lapierre},
doi = {10.1016/j.eururo.2021.06.010},
issn = {1873-7560},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Eur Urol},
volume = {80},
number = {4},
pages = {405--414},
abstract = {BACKGROUND: Oligorecurrent pelvic nodal relapse in prostatic cancer is a challenge for regional salvage treatments. Androgen depriving therapies (ADTs) are a mainstay in metastatic prostate cancer, and salvage pelvic radiotherapy may offer long ADT-free intervals for patients harboring regional nodal relapses.

OBJECTIVE: To assess the efficacy of the combination of ADT and salvage radiotherapy in men with oligorecurrent pelvic node relapses of prostate cancer.

DESIGN, SETTING, AND PARTICIPANTS: We performed an open-label, phase II trial of combined high-dose intensity-modulated radiotherapy and ADT (6 mo) in oligorecurrent (five or fewer) pelvic node relapses in prostate cancer, detected by fluorocholine positron-emission tomography computed tomography imaging.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was 2-yr progression-free survival defined as two consecutive prostate-specific antigen levels above the level at inclusion and/or clinical evidence of progression as per RECIST 1.1 and/or death from any cause.

RESULTS AND LIMITATIONS: Between August 2014 and July 2016, 67 patients were recruited in 15 centers. Half of the patients had received prior prostatic irradiation. The median age was 67.7 yr. After a median follow-up of 49.4 mo, 2- and 3-yr progression-free survival rates were 81% and 58%, respectively. Median progression-free survival was 45.3 mo. The median biochemical relapse-free survival (BRFS) was 25.9 mo. At 2 and 3 yr, the BRFS rates were 58% and 46%, respectively. Grade 2 + 2-yr genitourinary and gastrointestinal toxicities were 10% and 2%, respectively.

CONCLUSIONS: Combined high-dose salvage pelvic radiotherapy and ADT appeared to prolong tumor control in oligorecurrent pelvic node relapses in prostate cancer with limited toxicity. After 3 yr, nearly half of patients were in complete remission. Our study showed initial evidence of benefit, but a randomized trial is required to confirm this result.

PATIENT SUMMARY: In this report, we looked at the outcomes of combined high-dose salvage pelvic radiotherapy and 6-mo-long hormone therapy in oligorecurrent pelvic nodal relapse in prostatic cancer. We found that 46% of patients presenting with oligorecurrent pelvic node relapses in prostate cancer were in complete remission after 3 yr following combined treatment at the cost of limited toxicity.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Hoguin2021.06.11.447926,
title = {Evolutionary analysis of DNA methyltransferases in microeukaryotes: Insights from the model diatom Phaeodactylum tricornutum},
author = {Antoine Hoguin and Ouardia Ait Mohamed and Chris Bowler and Auguste Genovesio and Fabio Rocha Jimenez Vieira and Leila Tirichine},
url = {https://www.biorxiv.org/content/early/2021/06/11/2021.06.11.447926},
doi = {10.1101/2021.06.11.447926},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {bioRxiv},
publisher = {Cold Spring Harbor Laboratory},
abstract = {Cytosine DNA methylation is an important epigenetic mark in eukaryotes that is involved in the transcriptional control of mainly transposable elements in mammals, plants, and fungi. Eukaryotes encode a diverse set of DNA methyltransferases that were iteratively acquired and lost during evolution. The Stramenopiles-Alveolate-Rhizaria (SAR) lineages are a major group of ecologically important marine microeukaryotes that include the main phytoplankton classes such as diatoms and dinoflagellates. However, little is known about the diversity of DNA methyltransferases and their role in the deposition and maintenance of DNA methylation in microalgae. We performed a phylogenetic analysis of DNA methyltransferase families found in marine microeukaryotes and show that they encode divergent DNMT3, DNMT4, DNMT5 and DNMT6 enzymes family revisiting previously established phylogenies. Furthermore, we reveal a novel group of DNMTs with three classes of enzymes within the DNMT5 family. Using a CRISPR/Cas9 strategy we demonstrate that the loss of the DNMT5 gene correlates with a global depletion of DNA methylation and overexpression of transposable elements in the model diatom Phaeodactylum tricornutum. The study provides a pioneering view of the structure and function of a DNMT family in the SAR supergroup.Competing Interest StatementThe authors have declared no competing interest.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{armbrecht2021paleo,
title = {Paleo-diatom composition from Santa Barbara Basin deep-sea sediments: a comparison of 18S-V9 and diat-rbcL metabarcoding vs shotgun metagenomics},
author = {Linda Armbrecht and Raphael Eisenhofer and José Utge and Elizabeth C Sibert and Fabio Rocha and Ryan Ward and Juan José Pierella Karlusich and Leila Tirichine and Richard Norris and Mindi Summers and Chris Bowler},
year  = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {ISME Communications},
volume = {1},
number = {1},
pages = {1--10},
publisher = {Nature Publishing Group},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@misc{sanejouand2020framework,
title = {A framework for the next generation of stationary cosmological models},
author = {Yves-Henri Sanejouand},
url = {https://arxiv.org/abs/2005.07931},
year  = {2020},
date = {2020-12-28},
abstract = {According to a tired-light cosmological model where H(z) = H(0) (1 + z), the number density of galaxies has been nearly constant over the last 10 Gyr, at least, meaning that, as far as galaxies are concerned, the Universe has been stationary. On the other hand, an analysis of the luminosity distances of quasars and supernovae Ia shows that the Universe is far from being as transparent as assumed nowadays, the photon lifetime along the line-of-sight being one third of the Hubble time. The tired-light model advocated in the present study would be falsified if, for instance, the time-dilation of remote events were shown to have a general character, that is, if it were observed for phenomenons other than the light-curves of supernovae Ia.},
howpublished = {arxiv:2005.07931},
note = {working paper or preprint},
keywords = {out_lab},
pubstate = {published},
tppubtype = {misc}
}
@article{pmid33311449,
title = {Anti-PD1 therapy induces lymphocyte-derived exosomal miRNA-4315 release inhibiting Bim-mediated apoptosis of tumor cells},
author = {Nina Guyon and Delphine Garnier and Joséphine Briand and Arulraj Nadaradjane and Gwenola Bougras-Cartron and Judith Raimbourg and Mario Campone and Dominique Heymann and François M Vallette and Jean-Sébastien Frenel and Pierre-François Cartron},
doi = {10.1038/s41419-020-03224-z},
issn = {2041-4889},
year  = {2020},
date = {2020-12-11},
urldate = {2020-12-11},
journal = {Cell Death Dis},
volume = {11},
number = {12},
pages = {1048},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{10.1093/neuonc/noaa222.321,
title = {HGG-40. Exceptional synchronous occurence of a BRAF V600E mutant glioblastoma and a H3.3K27M mutant diffuse intrinsic Pontine glioma: a case report},
author = {Emilie De Carli and Blandine Boisselier and Luc Le Fournier and Stéphane Supiot and Coralie Mallebranche and Stéphanie Proust-Houdemont and Mylène Duplan and Isabelle Pellier and Audrey Rousseau},
url = {https://doi.org/10.1093/neuonc/noaa222.321},
doi = {10.1093/neuonc/noaa222.321},
issn = {1522-8517},
year  = {2020},
date = {2020-12-04},
urldate = {2020-01-01},
journal = {Neuro-Oncology},
volume = {22},
number = {Supplement_3},
pages = {iii351-iii351},
abstract = {We report herein the case of a 17-year-old female who presented with intracranial hypertension and diplopia. Magnetic resonance imaging showed a large left cystic and solid temporoparietal lesion, associated with an infiltrating lesion of the brainstem, hypointense in T1 and hyperintense in FLAIR sequences, without enhancement after injection of gadolinium. Complete resection of the parietal mass and biopsy of the brainstem lesion were performed. Histopathological analysis of the parietal mass showed glioblastoma (WHO grade IV) with no IDH1/2 or H3.3/H3.1 gene mutation detected by Sanger sequencing. Immunohistochemistry found the expression of the proteins of mismatch repair system. Whole exome and RNA sequencing identified a BRAF-V600E mutation. The brainstem lesion was a diffuse midline glioma, H3K27M-mutant (grade IV) according to the 2016 WHO classification. Pan-genomic SNP arrays of the 2 tumors showed distinct genetic alterations. The parietal glioblastoma displayed complex genomic alterations whereas the brainstem glioma harbored chromosome 7q gain, chromosome 9p and 10 losses, and RB, TP53 and CDKN2A homozygous deletions. The patient was treated by concomitant radiochemotherapy (according to Stupp protocol). After 12 cycles of temozolomide, there was complete remission persistant in the parietal lobe. The brainstem tumor was stable but progressed after 3 months of temozolomide discontinuation. Treatment with mTOR inhibitors was initiated. At 21-month follow-up, the patient remains with few symptoms. No predisposition syndrome was identified in the patient or her family. Concurrent glioblastomas with distinct driver gene mutations are exceptional.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{BELKACEMI2020892,
title = {Patterns of practice of androgen deprivation therapy combined to radiotherapy in favorable and unfavorable intermediate risk prostate cancer. Results of The PROACT Survey from the French GETUG Radiation Oncology group},
author = {Y Belkacemi and I Latorzeff and A Hasbini and G Coraggio and D Pasquier and A Toledano and C Hennequin and A Bossi and O Chapet and G Crehange and S Guerif and T Duberge and N Allouache and P Clavere and E Gross and S Supiot and D Azria and M Bolla and P Sargos},
url = {https://www.sciencedirect.com/science/article/pii/S1278321820302924},
doi = {https://doi.org/10.1016/j.canrad.2020.03.014},
issn = {1278-3218},
year  = {2020},
date = {2020-12-01},
urldate = {2020-12-01},
journal = {Cancer/Radiothérapie},
volume = {24},
number = {8},
pages = {892-897},
abstract = {Summary 
Purpose 
The intermediate-risk (IR) prostate cancer (PCa) group is heterogeneous in terms of prognosis. For unfavorable or favorable IR PCa treated by radiotherapy, the optimal strategy remains to be defined. In routine practice, the physician's decision to propose hormonal therapy (HT) is controversial. The PROACT survey aimed to evaluate pattern and preferences of daily practice in France in this IR population. 
Materials and methods 
A web questionnaire was distributed to French radiotherapy members of 91 centers of the Groupe d’Etude des Tumeurs Uro-Genitales (GETUG). The questionnaire included four sections concerning: (i) the specialists who prescribe treatments and multidisciplinary decisions (MTD) validation; (ii) the definition of IR subsets of patients; (iii) radiotherapy parameters; (iv) the pattern of practice regarding cardiovascular (CV) and (iv) metabolic evaluation. A descriptive presentation of the results was used. 
Results 
Among the 82 responses (90% of the centers), HT schedules and irradiation techniques were validated by specific board meetings in 54% and 45% of the centers, respectively. Three-fourths (76%) of the centers identified a subset of IR patients for a dedicated strategy. The majority of centers consider PSA&gt;15 (77%) and/or Gleason 7 (4+3) (87%) for an unfavorable IR definition. Overall, 41% of the centers performed systematically a CV evaluation before HT prescription while 61% consider only CV history/status in defining the type of HT. LHRH agonists are more frequently prescribed in both favorable (70%) and unfavorable (98%) IR patients. Finally, weight (80%), metabolic profile (70%) and CV status (77%) of patients are considered for follow-up under HT. 
Conclusion 
To the best of our knowledge, this is the first survey on HT practice in IR PCa. The PROACT survey indicates that three-quarters of the respondents identify subsets of IR-patients in tailoring therapy. The CV status of the patient is considered in guiding the HT decision, its duration and type of drug. 
Résumé 
Objectif de l’étude 
Le cancer de la prostate de risque intermédiaire est hétérogène en termes de pronostic. La stratégie optimale pour le cancer de la prostate de risque intermédiaire favorable ou défavorable n’est pas encore bien définie. Dans la pratique quotidienne, la décision médicale de proposer l’hormonothérapie reste controversée. L’enquête PROACT avait pour objectif d’évaluer les pratiques en France sur les indications de l’hormonothérapie associée à la radiothérapie. 
Matériel et méthodes 
Un questionnaire électronique a été distribué à 91 centres français membres du Groupe d’étude des tumeurs uro-génitales (GETUG). Le questionnaire incluait quatre sections : choix de l’hormonothérapie, pratiques de la radiothérapie, évaluation cardiovasculaire et métabolique avant l’hormonothérapie. Les résultats sont présentés de façon descriptive. 
Résultats 
Parmi les 82 réponses (90 % de centres), le schéma d’hormonothérapie et la technique d’irradiation sont validés lors de réunions de concertation pluridisciplinaires (RCP) dans respectuvement 54 % et 45 % des centrest. Trois-quarts (76 %) des centres ont déclaré identifier des sous-groupes de patients atteints de cancer de risque intermédiaire pour des stratégies dédiées. La plupart des centres considèrent une concentration de PSA de plus de 15ng/mL (77 %) et/ou un score de Gleason de 7 (4+3) (87 %) pour la définition du risque intermédiaire défavorable. Quarante et un pour cent des centres ont déclaré réaliser une évaluation cardiovasculaire systématique avant la prescription de l’hormonothérapie alors que 61 % ne considèrent que l’évaluation cardiovasculaire pour définir le type d’hormonothérapie. Les agonistes de la LHRH sont la forme la plus prescrite chez les patients atteints de cancer de risque intermédiaire favorable (70 %) ou défavorable (98 %). Le poids (80 %), le profil métabolique (70 %) et l’évaluation cardiovasculaire (77 %) des patients sont pris en compte pour le suivi des patients sous hormonothérapie. 
Conclusion 
À notre connaissance, PROACT est la première enquête sur les critères pratiques de la prescription de l’hormonothérapie dans le cancer de la prostate de risque intermédiaire. L’enquête montre que trois-quarts des centres français identifient les sous groupes de patients atteints de cancer de risque intermédiaire pour adapter le traitement. L’évaluation cardiovasculaire est prise en compte pour décider de l’indication, du type et de la durée de l’hormonothérapie.},
keywords = {Cancer prostatique, Hormone therapy, Intermediate risk, out_lab, PROACT, Prostate cancer, Radiothérapie, radiotherapy, Risque intermédiaire, Thérapie Hormonale},
pubstate = {published},
tppubtype = {article}
}
@article{MYLONA20201189,
title = {Rectal and Urethro-Vesical Subregions for Toxicity Prediction After Prostate Cancer Radiation Therapy: Validation of Voxel-Based Models in an Independent Population},
author = {Eugenia Mylona and Martin Ebert and Angel Kennedy and David Joseph and James Denham and Allison Steigler and Stephane Supiot and Oscar Acosta and Renaud Crevoisier},
url = {https://www.sciencedirect.com/science/article/pii/S0360301620314176},
doi = {https://doi.org/10.1016/j.ijrobp.2020.07.019},
issn = {0360-3016},
year  = {2020},
date = {2020-12-01},
urldate = {2020-01-01},
journal = {International Journal of Radiation Oncology*Biology*Physics},
volume = {108},
number = {5},
pages = {1189-1195},
abstract = {Purpose 
Recent voxel-based studies have shown that the dose to specific rectal and urethro-vesical subregions is predictive of toxicities after prostate cancer intensity modulated radiation therapy. The objective of this study was to validate the discriminatory power of these subregions with respect to the whole organs in a large independent population. 
Methods and Materials 
The validation cohort consisted of 450 patients from the TROG03.04-RADAR trial treated with 3-dimensional conformal radiation therapy at 66 to 74 Gy. Previous voxel-based analyses identified an inferoanterior rectal subregion as predictive of rectal bleeding and 5 subregions in the urethra and the posterior and superior part of the bladder as predictive of urinary incontinence, dysuria, retention, and hematuria. In the validation cohort, these subregions were segmented in each patient’s anatomy. Dose-volume histograms (DVHs) of the whole organs and the 6 subregions were compared bin-wise between patients with and without toxicities. The discriminatory power of DVHs for grade ≥2 toxicity endpoints was assessed using the area under the receiver operating characteristic curve (AUC). 
Results Subregion DVHs were significantly different between patients with and without toxicities for late rectal bleeding (V44-V74), acute urinary incontinence (V68-V72), late dysuria (V56-V68), and late retention (V14-V64). The dose to the rectal subregion and the whole rectum were equally predictive of rectal bleeding (V68; AUC = 0.61). The doses to 3 out of the 5 urethro-vesical subregions were found to be more predictive than the dose to the whole bladder: in the urethra for acute incontinence (V71 AUC = 0.69 vs V71 AUC = 0.66), in the posterior part of the bladder for late dysuria (V65 AUC = 0.66 vs V68 AUC = 0.59), and late retention (V39 AUC = 0.74 vs no significant AUC). 
Conclusions 
Three subregions located in the urethra and the bladder were successfully validated as more predictive of urinary toxicity than the whole bladder for urinary incontinence, retention, and dysuria. Sparing the posterior part of the bladder in particular in treatment planning may reduce the risk of late urinary retention.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{CARRIE20201204,
title = {Exclusive Hyperfractionated Radiation Therapy and Reduced Boost Volume for Standard-Risk Medulloblastoma: Pooled Analysis of the 2 French Multicentric Studies MSFOP98 and MSFOP 2007 and Correlation With Molecular Subgroups},
author = {Christian Carrie and Virginie Kieffer and Dominique Figarella-Branger and Julien Masliah-Planchon and Stéphanie Bolle and Valérie Bernier and Anne Laprie and Stéphane Supiot and Julie Leseur and Jean-Louis Habrand and Claire Alapetite and Christine Kerr and Christelle Dufour and Line Claude and Sophie Chapet and Aymeri Huchet and Pierre-Yves Bondiau and Alexandre Escande and Gilles Truc and Tan Dat Nguyen and Caroline Pasteuris and Céline Vigneron and Xavier Muracciole and Franck Bourdeaut and Romain Appay and Bernard Dubray and Carole Colin and Céline Ferlay and Sophie Dussart and Sylvie Chabaud and Laetitia Padovani},
url = {https://www.sciencedirect.com/science/article/pii/S0360301620337433},
doi = {https://doi.org/10.1016/j.ijrobp.2020.07.2324},
issn = {0360-3016},
year  = {2020},
date = {2020-12-01},
urldate = {2020-01-01},
journal = {International Journal of Radiation Oncology*Biology*Physics},
volume = {108},
number = {5},
pages = {1204-1217},
abstract = {Purpose 
Medulloblastoma has recently been characterized as a heterogeneous disease with 4 distinct molecular subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4, with a new definition of risk stratification. We report progression-free survival, overall survival, and long-term cognitive effects in children with standard–risk medulloblastoma exclusively treated with hyperfractionated radiation therapy (HFRT), reduced boost volume, and online quality control, and we explore the prognostic value of biological characteristics in this chemotherapy-naïve population. 
Methods and Materials 
Patients with standard–risk medulloblastoma were enrolled in 2 successive prospective multicentric studies, MSFOP 98 and MSFOP 2007, and received exclusive HFRT (36 Gy, 1 Gy/fraction twice daily) to the craniospinal axis followed by a boost at 68 Gy restricted to the tumor bed (1.5 cm margin), with online quality assurance before treatment. Patients with MYC or MYCN amplification were not excluded at the time of the study. We report progression-free survival and overall survival in the global population, and according to molecular subgroups as per World Health Organization 2016 molecular classification, and we present cognitive evaluations based on the Wechsler scale. 
Results Data from 114 patients included in the MSFOP 98 trial from December 1998 to October 2001 (n = 48) and in the MSFOP 2007 from October 2008 to July 2013 (n = 66) were analyzed. With a median follow-up of 16.2 (range, 6.4-19.6) years for the MSFOP 98 cohort and 6.5 (1.6-9.6) years for the MSFOP 2007 cohort, 5-year overall survival and progression-free survival in the global population were 84% (74%-89%) and 74% (65%-81%), respectively. Molecular classification was determined for 91 patients (WNT [n = 19], SHH [n = 12], and non-WNT/non-SHH [n = 60]—including group 3 [n = 9], group 4 [n = 29], and not specified [n = 22]). Our results showed more favorable outcome for the WNT-activated subgroup and a worse prognosis for SHH-activated patients. Three patients had isolated extra–central nervous system relapse. The slope of neurocognitive decline in the global population was shallower than that observed in patients with a normofractionated regimen combined with chemotherapy. 
Conclusions 
HFRT led to a 5-year survival rate similar to other treatments combined with chemotherapy, with a reduced treatment duration of only 6 weeks. We confirm the MSFOP 98 results and the prognostic value of molecular status in patients with medulloblastoma, even in the absence of chemotherapy. Intelligence quotient was more preserved in children with medulloblastoma who received exclusive HFRT and reduced local boost, and intelligence quotient decline was delayed compared with patients receiving standard regimen. HFRT may be appropriate for patients who do not consent to or are not eligible for prospective clinical trials; for patients from developing countries for whom aplasia or ileus may be difficult to manage in a context of high cost/effectiveness constraints; and for whom shortened duration of RT may be easier to implement.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Chabot2020,
title = {Relationships between DNA repair and RTK-mediated signaling pathways},
author = {Thomas Chabot and Yvonnick Cheraud and Fabrice Fleury},
url = {https://linkinghub.elsevier.com/retrieve/pii/S0304419X20302146},
doi = {10.1016/j.bbcan.2020.188495},
issn = {0304419X},
year  = {2020},
date = {2020-12-01},
journal = {Biochimica et Biophysica Acta (BBA) - Reviews on Cancer},
pages = {188495},
publisher = {Elsevier},
keywords = {team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Meresse2020,
title = {Fucoxanthin, a Marine-Derived Carotenoid from Brown Seaweeds and Microalgae: A Promising Bioactive Compound for Cancer Therapy},
author = {Sarah Méresse and Mostefa Fodil and Fabrice Fleury and Benoît Chénais},
url = {https://www.mdpi.com/1422-0067/21/23/9273},
doi = {10.3390/ijms21239273},
issn = {1422-0067},
year  = {2020},
date = {2020-12-01},
journal = {International Journal of Molecular Sciences},
volume = {21},
number = {23},
pages = {9273},
publisher = {Multidisciplinary Digital Publishing Institute},
abstract = {Fucoxanthin is a well-known carotenoid of the xanthophyll family, mainly produced by marine organisms such as the macroalgae of the fucus genus or microalgae such as Phaeodactylum tricornutum. Fucoxanthin has antioxidant and anti-inflammatory properties but also several anticancer effects. Fucoxanthin induces cell growth arrest, apoptosis, and/or autophagy in several cancer cell lines as well as in animal models of cancer. Fucoxanthin treatment leads to the inhibition of metastasis-related migration, invasion, epithelial–mesenchymal transition, and angiogenesis. Fucoxanthin also affects the DNA repair pathways, which could be involved in the resistance phenotype of tumor cells. Moreover, combined treatments of fucoxanthin, or its metabolite fucoxanthinol, with usual anticancer treatments can support conventional therapeutic strategies by reducing drug resistance. This review focuses on the current knowledge of fucoxanthin with its potential anticancer properties, showing that fucoxanthin could be a promising compound for cancer therapy by acting on most of the classical hallmarks of tumor cells.},
keywords = {angiogenesis, apoptosis, cancer, cell growth arrest, DNA repair, EMT, fucoxanthin, inflammation, invasion, migration, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{biomedicines8120548,
title = {Targeting Stereotactic Body Radiotherapy on Metabolic PET- and Immuno-PET-Positive Vertebral Metastases},
author = {Baptiste Pichon and Caroline Rousseau and Audrey Blanc-Lapierre and Gregory Delpon and Ludovic Ferrer and Vincent Libois and Matthieu Le Turnier and Cédric Lenoble and Caroline Bodet-Milin and David M. Goldenberg and Françoise Kraeber-Bodere and Stéphane Supiot},
url = {https://www.mdpi.com/2227-9059/8/12/548},
doi = {10.3390/biomedicines8120548},
issn = {2227-9059},
year  = {2020},
date = {2020-11-28},
urldate = {2020-01-01},
journal = {Biomedicines},
volume = {8},
number = {12},
abstract = {(1) Background: Stereotactic body radiotherapy (SBRT) for vertebral metastases (VM) allows the delivery of high radiation doses to tumors while sparing the spinal cord. We report a new approach to clinical target volume (CTV) delineation based on anti-carcinoembryonic antigen (CEA) positron emission tomography (pretargeted immuno-PET; “iPET”) in patients with metastatic breast cancer (BC) or medullary thyroid cancer (MTC). (2) Methods: All patients underwent iPET, spine magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) using 18F-deoxyglucose (FDG) for BC or 18F-dihydroxy-phenylalanine (F-DOPA) for MTC. Vertebrae locations and vertebral segments of lesions were recorded and the impact on CTV delineation was evaluated. (3) Results: Forty-six VM eligible for SBRT following iPET were evaluated in eight patients (five BC, three MTC). Eighty-one vertebral segments were detected using MRI, 26 with FDG or F-DOPA PET/CT, and 70 using iPET. iPET was able to detect more lesions than MRI for vertebral bodies (44 vs. 34). iPET-based delineation modified MRI-based CTV in 70% (32/46) of cases. (4) Conclusion: iPET allows a precise mapping of affected VM segments, and adds complementary information to MRI in the definition of candidate volumes for VM SBRT. iPET may facilitate determining target volumes for treatment with stereotactic body radiotherapy in metastatic vertebral disease.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{SARGOS2020S17,
title = {A Phase III Randomized Trial Comparing Adjuvant versus Early Salvage Radiotherapy, Both Combined with Short-term Androgen Deprivation Therapy, following a Radical Prostatectomy: Initial Results of the GETUG-AFU 17 Study [NCT00667069]},
author = {P Sargos and S Chabaud and I Latorzeff and N Magne and A Benyoucef and S Supiot and D Pasquier and S Abdiche and O Gilliot and P Graff and M Silva and P Bergerot and P Baumann and Y Belkacemi and D Azria and S Nenan and PM Richaud},
url = {https://www.sciencedirect.com/science/article/pii/S0360301620335197},
doi = {https://doi.org/10.1016/j.ijrobp.2020.07.2100},
issn = {0360-3016},
year  = {2020},
date = {2020-11-01},
urldate = {2020-01-01},
journal = {International Journal of Radiation Oncology*Biology*Physics},
volume = {108},
number = {3, Supplement},
pages = {S17-S18},
note = {Proceedings of the American Society for Radiation Oncology},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{THUREAU2020e195,
title = {French randomized phase III study between: Standard Treatment with or without SBRT in Solid Tumors Patients with Between 1 and 3 Bone-only Metastases (STEREO-OS)},
author = {S Thureau and N Bonnet and V Marchesi and A Lisbona and S Supiot and JC Faivre},
url = {https://www.sciencedirect.com/science/article/pii/S0360301620328431},
doi = {https://doi.org/10.1016/j.ijrobp.2020.07.1424},
issn = {0360-3016},
year  = {2020},
date = {2020-11-01},
urldate = {2020-01-01},
journal = {International Journal of Radiation Oncology*Biology*Physics},
volume = {108},
number = {3, Supplement},
pages = {e195},
note = {Proceedings of the American Society for Radiation Oncology},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
@article{SARGOS2020733,
title = {GETUG-AFU 17 : étude de phase III randomisée comparant la radiothérapie adjuvante à la radiothérapie de rattrapage précoce, combinées à l’hormonothérapie courte, pour les patients présentant un cancer de la prostate traité par prostatectomie radicale},
author = {P Sargos and S Chabaud and I Latorzeff and N Magné and A Benyoucef and S Supiot and D Pasquier and S Abdiche and O Gilliot and P Graff-Cailleaud and M Silva and P Bergerot and P Baumann and Y Belkacemi and D Azria and M Brihou and M Soulié and P Richaud},
url = {https://www.sciencedirect.com/science/article/pii/S1166708720303079},
doi = {https://doi.org/10.1016/j.purol.2020.07.071},
issn = {1166-7087},
year  = {2020},
date = {2020-11-01},
urldate = {2020-01-01},
journal = {Progrès en Urologie},
volume = {30},
number = {13},
pages = {733-734},
abstract = {Objectifs 
La radiothérapie adjuvante (aRT) réduit le risque de rechute biochimique chez les patients atteints d’un cancer de la prostate traités par une prostatectomie radicale (RP). L’étude GETUG-AFU 17 a comparé l’efficacité et la toxicité de l’aRT par rapport à la radiothérapie de rattrapage précoce (sRT), associée à un traitement hormonal. 
Méthodes 
Cette étude multicentrique, de phase III, randomisée et contrôlée, a été réalisée dans 46 centres français. Les patients devaient être âgés de plus de 18 ans, avec un statut Eastern Cooperative Oncology Group ≤1, une maladie classée pT3-4 et marges positives, pNx ou pN0, avec PSA postopératoire ≤0,1ng/mL. Les patients ont été randomisés (par minimisation ; 1 : 1) après RP, entre aRT ou observation avec sRT, combiné avec 6 mois de triptoréline. Le critère principal était la survie sans événement (EFS). Les critères d’évaluation secondaires étaient la survie globale (SG), la survie sans métastase (MFS), l’incidence des toxicités aiguës et tardives (CTCAE v3.0) et la qualité de vie (QoL) (échelles QLQ-C30 et PR-25). Cet essai est enregistré sous le numéro ClinicalTrials.gov NCT00667069. 
Résultats Entre le 7 mars 2008 et le 23 juin 2016, 424 patients ont été inclus. Nous avions prévu d’inclure 718 patients. Les inclusions ont été interrompues prématurément en raison de taux d’événements étonnamment bas. Les caractéristiques initiales des patients et de leur tumeur étaient bien équilibrées entre les bras. Le suivi médian était de 75, 3 mois (IQR : 50–100). Lors de l’analyse, 115/212 patients (54 %) du bras sRT avaient commencé le traitement. Avec 58 événements, l’EFS à 5 ans était de 92 % (IC95 % : 86–95) dans le bras aRT et de 90 % (IC95 % : 85–94) dans le bras sRT (HR=0,81 [IC95 % : 0,48–1,36] ; test du log-rank p=0,42). Le taux de SG à 5 ans était de 96 % (IC95 % : 92–98) dans le bras aRT et de 99 % (IC95 % : 96–100) dans le bras sRT (HR=1,60 [IC95 % : 0,71–3,60] ; p=0,25). Les toxicités génito-urinaires de grade ≥2 étaient plus importantes dans le bras aRT (27 % vs 7 % ; p&lt;0,0001). La dysfonction érectile de grade ≥2 était majorée dans le bras aRT (p&lt;0,0001). Les changements dans tous les domaines du QLQ-C30 étaient similaires dans les deux bras (p=0,11). 
Conclusion 
L’étude GETUG-AFU 17 n’a montré aucun bénéfice en EFS pour l’aRT par rapport à la sRT. L’aRT a augmenté le risque de toxicité génito-urinaire et de dysfonction érectile. Une stratégie de sRT précoce pourrait épargner aux hommes la RT et la toxicité associée.},
note = {114e congrès français d’urologie},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{2512c408dbd041e2a96bc992f35deff9,
title = {Current radiotherapy practice for children with metastases from solid tumors: SIOPE survey analysis},
author = {S Huijskens and P Kroon and C Demiroz Abakay and B Timmermann and J Giralt and M Gaze and S Harrabi and G Scarzello and A Alexopoulou and L Padovani and A Escande and L Gandola and S Supiot and M Chojnacka and J Bokun and A Napieralska and B Rombi and J H Maduro and S Bolle and A Mussano and H Mandeville and L Claude and E Seravalli and GO Janssens},
url = {https://www.sciencedirect.com/science/article/pii/S016781402100476X},
doi = {10.1016/S0167-8140(21)00476-X},
issn = {0167-8140},
year  = {2020},
date = {2020-11-01},
urldate = {2020-11-01},
journal = {Radiotherapy and Oncology},
volume = {152},
pages = {S251--S253},
publisher = {ELSEVIER IRELAND LTD},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{SUPIOT2020S105,
title = {OC-0210: Salvage radiotherapy in oligorecurrent pelvic node relapses of prostate cancer : a phase 2 trial},
author = {S Supiot and D Pasquier and X Buthaud and N Magne and V Becckendorf and G Crehange and P Pommier and G Loos and A Hasbini and I Latorzeff and M Silva and F Denis and L Campion and L Vaugier and A Blanc-Lapierre},
url = {https://www.sciencedirect.com/science/article/pii/S0167814021002346},
doi = {https://doi.org/10.1016/S0167-8140(21)00234-6},
issn = {0167-8140},
year  = {2020},
date = {2020-11-01},
urldate = {2020-01-01},
journal = {Radiotherapy and Oncology},
volume = {152},
pages = {S105},
note = {ESTRO 2020 - Online Congress, 28 November to 1 December 2020},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{HUIJSKENS2020S251,
title = {OC-0454: Current radiotherapy practice for children with metastases from solid tumors: SIOPE survey analysis},
author = {S Huijskens and P Kroon and C Demiroz Abakay and B Timmermann and J Giralt and M Gaze and S Harrabi and G Scarzello and A Alexopoulou and L Padovani and A Escande and L Gandola and S Supiot and M Chojnacka and J Bokun and A Napieralska and B Rombi and JH Maduro and S Bolle and A Mussano and H Mandeville and L Claude and E Seravalli and GO Janssens},
url = {https://www.sciencedirect.com/science/article/pii/S016781402100476X},
doi = {https://doi.org/10.1016/S0167-8140(21)00476-X},
issn = {0167-8140},
year  = {2020},
date = {2020-11-01},
urldate = {2020-01-01},
journal = {Radiotherapy and Oncology},
volume = {152},
pages = {S251-S253},
note = {ESTRO 2020 - Online Congress, 28 November to 1 December 2020},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{MYLONA2020S829,
title = {PO-1535: Machine Learning and Oversampling techniques to predict urinary toxicity after prostate cancer RT},
author = {E Mylona and F Filias and M Ibrahim and S Supiot and N Magne and G Crehange and M Hatt and O Acosta and R De Crevoisier},
url = {https://www.sciencedirect.com/science/article/pii/S016781402101553X},
doi = {https://doi.org/10.1016/S0167-8140(21)01553-X},
issn = {0167-8140},
year  = {2020},
date = {2020-11-01},
urldate = {2020-01-01},
journal = {Radiotherapy and Oncology},
volume = {152},
pages = {S829},
note = {ESTRO 2020 - Online Congress, 28 November to 1 December 2020},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@inproceedings{9288124,
title = {Ensemble Learning for Prediction of Toxicity in Prostate Cancer Radiotherapy: Comparison Between Stacking and Genetic Algorithm Weighted Voting},
author = {Filippos Filias and Eugenia Mylona and Kostas Blekos and Stephane Supiot and Renaud Crevoisier and Oscar Acosta},
doi = {10.1109/BIBE50027.2020.00150},
year  = {2020},
date = {2020-10-26},
urldate = {2020-10-26},
booktitle = {2020 IEEE 20th International Conference on Bioinformatics and Bioengineering (BIBE)},
pages = {884-889},
abstract = {Prediction of urinary toxicity after prostate cancer radiotherapy (RT) is remarkably challenging. Not only it is a multifaceted phenomenon, encompassing different symptoms (retention, dysuria, haematuria, etc.), but also a multifactorial problem, as it depends on both patient-specific clinical factors, individual biological parameters, and dosimetric patterns. Thus, there are a plethora of potential predictors compared to the paucity of available symptom-specific toxicity data. On top of that, in elder patients, urinary complications are not necessarily treatment-related which introduces important noise to the urinary toxicity assessment. In recent years, a growing interest in machine learning (ML) appears within the radiotherapy community. The goal of ML algorithms is to learn from existing data to recognize patterns in the population and make informed decisions. The purpose of this study was to implement two advanced heterogeneous ensemble methods, namely Stacking and Genetic Algorithm-based Weighted Average Voting for improving urinary toxicity prediction in the case of prostate cancer radiotherapy. Our analysis demonstrated that both GA-based Voting (AUC =0.66) and Stacking (AUC =0.80) outperformed the standard Weighted Voting classifier (AUC =0.66). In conclusion, Genetic Algorithm-based Weighted Average Voting may improve prediction performance compared to individual classifiers or conventional voting ensembles but at high computational cost. Stacking, on the other hand, appears significantly more powerful for predicting urinary toxicity at less computational cost.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {inproceedings}
}
@inproceedings{desrousseaux2020treatmentb,
title = {Current Radiotherapy Practice With Curative Intent for Children With Metastases From Solid Tumors Across SIOPE Affiliated Countries: A Multicenter Survey Analysis},
author = {S Huijskens and P Kroon-Van Loon and L Gandola and S Bolle and M Gaze and S Supiot and C Demiroz Abakay and A Alexopoulou and J Bokun and M Chojnacka and A Escande and J Giralt and S Harrabi and J Maduro and H Mandeville and A Mussano and A Napieralska and L Padovani and G Scarzello and B Timmermann and L Claude and E Seravalli and G Janssens},
year  = {2020},
date = {2020-10-23},
urldate = {2020-10-23},
booktitle = {PEDIATRIC BLOOD & CANCER},
volume = {67},
pages = {S300--S301},
organization = {WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
@inproceedings{desrousseaux2020treatment,
title = {Treatment for Recurrent Ependymoma: A Retrospective Study Frome the Societe Francaise De Lutte Contre LEs Cancers Et Leucemies De L'enfant Et De L'adolescent (SFCE)},
author = {J Desrousseaux and A Ducassou and L Chaltiel and L Padovani and S Bolle and J-L Habrand and L Claude and C Carrie and X Muracciole and A Escande and C Alapetite and S Supiot and V Bernier-Chastagner and A Huchet and J Leseur and C Kerr and G Truc and S Servagi-Vernat and P Leblond and A-I Bertozzi-Salomon and S Boetto and A Sevely and F Tensaouti and A Laprie},
year  = {2020},
date = {2020-10-13},
urldate = {2020-01-01},
booktitle = {PEDIATRIC BLOOD & CANCER},
volume = {67},
pages = {S48--S49},
organization = {WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA},
keywords = {out_lab},
pubstate = {published},
tppubtype = {inproceedings}
}
@article{Bertorelle_2020,
title = {Covalent anchoring of atomically precise glutathione-protected gold nanoclusters on graphene oxide nanosheets},
author = {Franck Bertorelle and Srestha Basu and Hussein Fakhouri and Martina Peri{ć} Bakuli ć and Pierre Mignon and Isabelle Russier-Antoine and Pierre-Fran ç and Sabu Thomas and Nandakumar Kalarikkal and Rodolphe Antoine},
url = {https://doi.org/10.1088/2632-959x/abbe31},
doi = {10.1088/2632-959x/abbe31},
year  = {2020},
date = {2020-10-01},
journal = {Nano Express},
volume = {1},
number = {3},
pages = {030005},
publisher = {IOP Publishing},
abstract = {This paper describes the development of a novel method of producing nanocomposites consisting of gold nanoclusters anchored on graphene oxide nanosheets in a cost-effective and reproducible manner. The novelty of the technique hinges on the covalent functionalization of atomically precise subnanometer gold clusters protected by glutathione (Au15SG13 and Au25SG18) on to graphene oxide (GO) nanosheets according to the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride crosslinking method, using the existing carboxylic groups present both at the surfaces of the nanoclusters and the GO nanosheets. The atomic precision of glutathione-protected gold nanoclusters was evidenced by electrospray ionization mass spectrometry. The formed hybrid nanocomposites were characterized by TEM measurements and exhibit nonlinear optical properties characteristic of GO, in particular a strong second harmonic scattering response as well as a multi-photon excited fluorescence spectrum characterized by a broad band in the visible range between 350 and 700 nm. Atomically precise nanoclusters covalently linked to GO nanosheets are therefore promising for new applications in the areas of optoelectronics and photovoltaics.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{JOUGLAR2020594,
title = {Faut-il moduler les contraintes de dose dans les organes à risque lors d’une irradiation en association avec un traitement anticancéreux systémique ?},
author = {E Jouglar and J Doyen and S Supiot},
url = {https://www.sciencedirect.com/science/article/pii/S1278321820301712},
doi = {https://doi.org/10.1016/j.canrad.2020.05.010},
issn = {1278-3218},
year  = {2020},
date = {2020-10-01},
urldate = {2020-01-01},
journal = {Cancer/Radiothérapie},
volume = {24},
number = {6},
pages = {594-601},
abstract = {Résumé 
Les stratégies thérapeutiques anticancéreuses associant une radiothérapie et un traitement systémique incluant chimiothérapie, hormonothérapie mais aussi plus récemment immunothérapie et thérapie ciblée sont de pratique courante. Pourtant les traitements combinés concomitants ou séquentiels sont souvent à l’origine d’une augmentation de la toxicité. Pour augmenter le bénéfice d’une combinaison thérapeutique, la question d’une modulation de la dose délivrée aux organes à risque se pose afin de diminuer les effets indésirables. Une revue de la littérature sur les toxicités limitantes en lien avec les stratégies associant radiothérapie et traitements systémiques a été menée. Cette étude a permis de caractériser quatre situations parmi lesquelles 1) des contre-indications de certaines associations en raison de toxicité inacceptable ou recommandations de prudence avec limitations des indications, de la dose prescrite ou l’application de contraintes aux organes à risque plus sévères, 2) des traitements combinés sans toxicité surajoutée ne plaidant pas en faveur d’une modulation des contraintes de dose habituelles, 3) des associations semblant augmenter le risque de toxicité en faveur d’une modulation de la dose aux organe à risque, 4) des traitements combinés avec données de tolérance limitées ou inconnues, raison pour laquelle l’association n’est recommandée que dans le cadre d’un essai thérapeutique. 
Therapeutic strategies combining irradiation and drugs including chemotherapy, hormonotherapy, but also more recently targeted therapy and immunotherapy are routinely used for cancer treatment. Nevertheless, combined treatments usually lead to a rise in toxicity. In order to increase the therapeutic ratio in favour of a multimodality treatment, adapting dose constraints to organs at risk may be the key to lower the risk of toxicity. A review of the literature was conducted, focusing on the toxicity in dose-limiting organs at risk when radiation therapy is associated with drugs. Four situations were differentiated, including : 1) some contraindicated combinations due to an inacceptable increased of toxicity, or recommendations of careful use with restricted indications, reduction in prescribed dose, or severe dose constraints to organs at risk, 2) combined treatments without increased toxicity with no arguments for adjusted dose constraints, 3) associations with higher risk of toxicity, for which dose constraints could be adapted, 4) combined therapies with limited tolerance data, prohibiting their use out of clinical trials.},
note = {31e Congrès national de la Société française de radiothérapie oncologique},
keywords = {Contraintes de dose, Dose constraints, Drugs, Organe à risque, Organs at risk, out_lab, Radiothérapie, radiotherapy, Traitement systémique},
pubstate = {published},
tppubtype = {article}
}
@article{CHARGARI2020602,
title = {Traitement des effets tardifs après la radiothérapie : quoi de neuf ?},
author = {C Chargari and S Supiot and C Hennequin and A Chapel and J-M. Simon},
url = {https://www.sciencedirect.com/science/article/pii/S1278321820301773},
doi = {https://doi.org/10.1016/j.canrad.2020.06.007},
issn = {1278-3218},
year  = {2020},
date = {2020-10-01},
urldate = {2020-01-01},
journal = {Cancer/Radiothérapie},
volume = {24},
number = {6},
pages = {602-611},
abstract = {Résumé 
Les mécanismes des lésions radio-induites tardives sont la résultante de phénomènes multiples et complexes, avec de nombreux acteurs cellulaires et tissulaires intriqués. Le continuum biologique entre effets aigus et effets tardifs après irradiation sera décrit, avec en premier lieu une rupture d’homéostasie qui conduit à des redistributions cellulaires. De nouveaux éclairages sur la toxicité tardive seront enfin abordés. La radiosensibilité individuelle est un facteur primordial dans le développement de toxicité tardive, et les cliniciens ont un besoin urgent de disposer de tests prédictifs qui permettraient de proposer une radiothérapie réellement personnalisée. La mise au point est faite sur les différents tests fonctionnels et génétiques en cours de validation. La prise en charge des effets secondaires de la radiothérapie reste un problème fréquent pour l’oncologue radiothérapeute, et un point est fait sur les traitements qui peuvent être proposés dans certaines situations cliniques particulières. Enfin, une prise en charge innovante est développée pour les patients atteints d’effets secondaires importants après radiothérapie pelvienne, la greffe de cellules souches mésenchymateuses, avec la présentation du protocole « Prisme » actuellement ouvert au recrutement des patients. 
Mechanisms of late radio-induced lesions are the result of multiple and complex phenomena, with many entangled cellular and tissue factors. The biological continuum between acute and late radio-induced effects will be described, with firstly a break in homeostasis that leads to cellular redistributions. New insights into late toxicity will finally be addressed. Individual radiosensitivity is a primary factor for the development of late toxicity, and clinicians urgently need predictive tests to offer truly personalized radiation therapy. An update will be made on the various functional and genetic tests currently being validated. The management of radio-induced side effects remains a frequent issue for radiation oncologists, and an update will be made for certain specific clinical situations. Finally, an innovative management for patients with significant side effects after pelvic radiotherapy will be developed, involved mesenchymal stem cell transplantation, with the presentation of the “PRISME” protocol currently open to patients recruitment.},
note = {31e Congrès national de la Société française de radiothérapie oncologique},
keywords = {Cellules souches mésenchymateuses, Effets secondaires de la radiothérapie, Mesenchymal stem cells, out_lab, Radiation-induced toxicity, Radiosensibilité, Radiosensitivity, Radiothérapie, radiotherapy, Side effects of radiation therapy, Toxicité radio-induite},
pubstate = {published},
tppubtype = {article}
}
@article{DORE2020769,
title = {Prise en charge d’une tachycardie ventriculaire par radiothérapie en conditions stéréotaxiques : première expérience},
author = {M Doré and S Josset and E Mervoyer and J-B Gourraud and M Bonnin and P Cadot and S Chiavassa and G Kerdanet and J Lebreton and H Lorand and T Marsac and M Raimond and S Rousset and J-M Serfaty and G Delpon and S Supiot},
url = {https://www.sciencedirect.com/science/article/pii/S1278321820302031},
doi = {https://doi.org/10.1016/j.canrad.2020.08.004},
issn = {1278-3218},
year  = {2020},
date = {2020-10-01},
urldate = {2020-01-01},
journal = {Cancer/Radiothérapie},
volume = {24},
number = {6},
pages = {769-770},
abstract = {Introduction et but de l’étude 
Le traitement non invasif de la tachycardie ventriculaire par irradiation en conditions stéréotaxiques est une technique émergente. Nous présentons le premier cas pris en charge dans notre institut. 
Matériel et méthodes 
Il s’agit d’un homme de 68 ans pris en charge pour une hyperexcitabilité ventriculaire sévère à un mois d’un syndrome coronarien antérieur étendu, persistante malgré un traitement médical intense. L’ablation par radiofréquence a été récusée par la présence d’un thrombus intraventriculaire gauche. La pose d’un défibrillateur automatique implantable à double chambre a été réalisée. Devant la persistance d’accès de tachycardie ventriculaire soutenue devenant réfractaire aux chocs électriques internes, une de radiothérapie en conditions stéréotaxiques a été proposée. Après fabrication d’une contention thoracique thermoformée, une scanographie dosimétrique quadridimensionnelle et une scanographie en apnée expiratoire ont été réalisées. Les images ont été recalées avec celles de la coroscanographie diagnostique réalisée avant la pose du défibrillateur automatique implantable. La cible a été définie de manière consensuelle (radiothérapeute, cardiologue, radiologue) d’après les données morphologiques et électriques correspondant à deux volumes distincts en périphérie de la zone de myocarde infarcie et après identification de deux trajets de tachycardie ventriculaire antérieur et postérieur. Les mouvements respiratoires et cardiaques ont été pris en compte. Il a ensuite été appliqué une marge isotropique de 5mm afin de tenir compte des incertitudes de repositionnement, portant le volume cible prévisionnel à 75 cm3. La planification a utilisé une technique d’arcthérapie conformationnelle dynamique par photons de 6 MV du Novalis TrueBeam™. 
Résultats et analyse statistique 
La prescription a été de 25Gy à la périphérie du volume cible prévisionnel. L’indice de conformation était de 2,0 et l’indice de gradient de 8,4. La dose moyenne au cœur était de 8,8Gy, et la dose maximale dans l’artère coronaire droite et la circonflexe était respectivement de 7,5Gy et 15,1Gy. Après désactivation du défibrillateur automatique implantable et mise en place d’une surveillance cardiaque, le repositionnement du patient a été ajusté à l’aide d’une tomographie conique et de la scopie, avec recalage sur l’extrémité de la sonde ventriculaire droite du défibrillateur automatique implantable. La tolérance immédiate a été correcte, en dehors de nausées de grade 2. Un sevrage progressif des antiarythmiques a pu être réalisé. Une hyperexcitabilité sous forme d’extrasystoles ventriculaires isolées a persisté, sans récidive de troubles ventriculaires soutenus. 
Conclusion 
Cette expérience confirme la faisabilité et l’efficacité à court terme du traitement de la tachycardie ventriculaire réfractaire par irradiation en conditions stéréotaxiques. Un travail est à mener pour une meilleure définition de la cible à partir d’imagerie morphologique et électrophysiologique additionnelles et sur une faisabilité en technique de traitement modulée en intensité (VMAT). L’objectif thérapeutique doit être démontré dans une étude de phase II.},
note = {31e Congrès national de la Société française de radiothérapie oncologique},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{SARGOS20201341,
title = {Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial},
author = {Paul Sargos and Sylvie Chabaud and Igor Latorzeff and Nicolas Magné and Ahmed Benyoucef and Stéphane Supiot and David Pasquier and Menouar Samir Abdiche and Olivier Gilliot and Pierre Graff-Cailleaud and Marlon Silva and Philippe Bergerot and Pierre Baumann and Yazid Belkacemi and David Azria and Meryem Brihoum and Michel Soulié and Pierre Richaud},
url = {https://www.sciencedirect.com/science/article/pii/S147020452030454X},
doi = {https://doi.org/10.1016/S1470-2045(20)30454-X},
issn = {1470-2045},
year  = {2020},
date = {2020-10-01},
urldate = {2020-01-01},
journal = {The Lancet Oncology},
volume = {21},
number = {10},
pages = {1341-1352},
abstract = {Summary 
Background 
Adjuvant radiotherapy reduces the risk of biochemical progression in prostate cancer patients after radical prostatectomy. We aimed to compare adjuvant versus early salvage radiotherapy after radical prostatectomy, combined with short-term hormonal therapy, in terms of oncological outcomes and tolerance. 
Methods 
GETUG-AFU 17 was a randomised, open-label, multicentre, phase 3 trial done at 46 French hospitals. Men aged at least 18 years who had an Eastern Cooperative Oncology Group performance status of 1 or less, localised adenocarcinoma of the prostate treated with radical prostatectomy, who had pathologically-staged pT3a, pT3b, or pT4a (with bladder neck invasion), pNx (without pelvic lymph nodes dissection), or pN0 (with negative lymph nodes dissection) disease, and who had positive surgical margins were eligible for inclusion in the study. Eligible patients were randomly assigned (1:1) to either immediate adjuvant radiotherapy or delayed salvage radiotherapy at the time of biochemical relapse. Random assignment, by minimisation, was done using web-based software and stratified by Gleason score, pT stage, and centre. All patients received 6 months of triptorelin (intramuscular injection every 3 months). The primary endpoint was event-free survival. Efficacy and safety analyses were done on the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT00667069. 
Findings Between March 7, 2008, and June 23, 2016, 424 patients were enrolled. We planned to enrol 718 patients, with 359 in each study group. However, on May 20, 2016, the independent data monitoring committee recommended early termination of enrolment because of unexpectedly low event rates. At database lock on Dec 19, 2019, the overall median follow-up time from random assignment was 75 months (IQR 50–100), 74 months (47–100) in the adjuvant radiotherapy group and 78 months (52–101) in the salvage radiotherapy group. In the salvage radiotherapy group, 115 (54%) of 212 patients initiated study treatment after biochemical relapse. 205 (97%) of 212 patients started treatment in the adjuvant group. 5-year event-free survival was 92% (95% CI 86–95) in the adjuvant radiotherapy group and 90% (85–94) in the salvage radiotherapy group (HR 0·81, 95% CI 0·48–1·36; log-rank p=0·42). Acute grade 3 or worse toxic effects occurred in six (3%) of 212 patients in the adjuvant radiotherapy group and in four (2%) of 212 patients in the salvage radiotherapy group. Late grade 2 or worse genitourinary toxicities were reported in 125 (59%) of 212 patients in the adjuvant radiotherapy group and 46 (22%) of 212 patients in the salvage radiotherapy group. Late genitourinary adverse events of grade 2 or worse were reported in 58 (27%) of 212 patients in the adjuvant radiotherapy group versus 14 (7%) of 212 patients in the salvage radiotherapy group (p&lt;0·0001). Late erectile dysfunction was grade 2 or worse in 60 (28%) of 212 in the adjuvant radiotherapy group and 17 (8%) of 212 in the salvage radiotherapy group (p&lt;0·0001). 
Interpretation 
Although our analysis lacked statistical power, we found no benefit for event-free survival in patients assigned to adjuvant radiotherapy compared with patients assigned to salvage radiotherapy. Adjuvant radiotherapy increased the risk of genitourinary toxicity and erectile dysfunction. A policy of early salvage radiotherapy could spare men from overtreatment with radiotherapy and the associated adverse events. 
Funding 
French Health Ministry and Ipsen.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@phdthesis{chabot2020modulation,
title = {Modulation de l'activité du Rad51 par le récepteur tyrosine kinase c-Met dans la réparation des cassures double-brin de l'ADN},
author = {Thomas Chabot},
url = {https://www.theses.fr/2020NANT1013},
year  = {2020},
date = {2020-10-01},
school = {Université de Nantes},
abstract = {L'instabilité génomique due à la dérégulation des voies de réparation de l'ADN peut être à l’initiation de cancer et entraîner par la suite une résistance à la chimiothérapie et à la radiothérapie. La compréhension de ces mécanismes biologiques est donc essentielle dans la lutte contre le cancer. RAD51 est la protéine centrale de la voie de réparation des cassures double-brin de l'ADN par recombinaison homologue. Cette réparation conduit à une réparation fidèle de l'ADN. L'activité recombinase de la protéine RAD51 est finement régulée par des modifications post- traductionnelles telles que la phosphorylation. Au cours de la dernière décennie, de plus en plus d’études, suggèrent l'existence d'une relation entre les récepteurs à activité tyrosine kinases, souvent suractivés et impliqués dans l’agressivité et la prolifération cancéreuse, et la réparation de l'ADN. Parmi ces récepteurs à activité tyrosine kinases, le duo c-Met/HGF-SF est souvent muté, sur exprimé ou activé constitutivement dans de nombreux cancers et son inhibition a été montrée comme induisant une diminution de la réparation par recombinaison homologue. Au travers de cette thèse, nous montrons pour la première fois que c-Met est capable de phosphoryler la protéine RAD51 sur quatre résidus tyrosine localisés principalement dans l'interface monomère- monomère du nucléofilament de la recombinase humaine. Nous montrons l’implication de ces phosphorylations sur l’activité de RAD51 dans les différentes étapes de la recombinaison homologue. L'ensemble des résultats obtenus suggère le rôle possible de ces modifications dans la régulation de RAD51 et souligne l'importance de c-Met dans la réponse aux lésions de l'ADN.},
note = {294 pages},
keywords = {team 3, thesis},
pubstate = {published},
tppubtype = {phdthesis}
}
@article{Ait-Mohamed2020,
title = {PhaeoNet: A Holistic RNAseq-Based Portrait of Transcriptional Coordination in the Model Diatom Phaeodactylum tricornutum},
author = {Ouardia Ait-Mohamed and Anna M G {Novák Vanclová} and Nathalie Joli and Yue Liang and Xue Zhao and Auguste Genovesio and Leila Tirichine and Chris Bowler and Richard G Dorrell},
url = {https://pubmed.ncbi.nlm.nih.gov/33178253/},
doi = {10.3389/fpls.2020.590949},
issn = {1664462X},
year  = {2020},
date = {2020-10-01},
journal = {Frontiers in Plant Science},
volume = {11},
publisher = {Frontiers Media S.A.},
abstract = {Transcriptional coordination is a fundamental component of prokaryotic and eukaryotic cell biology, underpinning the cell cycle, physiological transitions, and facilitating holistic responses to environmental stress, but its overall dynamics in eukaryotic algae remain poorly understood. Better understanding of transcriptional partitioning may provide key insights into the primary metabolism pathways of eukaryotic algae, which frequently depend on intricate metabolic associations between the chloroplasts and mitochondria that are not found in plants. Here, we exploit 187 publically available RNAseq datasets generated under varying nitrogen, iron and phosphate growth conditions to understand the co-regulatory principles underpinning transcription in the model diatom Phaeodactylum tricornutum. Using WGCNA (Weighted Gene Correlation Network Analysis), we identify 28 merged modules of co-expressed genes in the P. tricornutum genome, which show high connectivity and correlate well with previous microarray-based surveys of gene co-regulation in this species. We use combined functional, subcellular localization and evolutionary annotations to reveal the fundamental principles underpinning the transcriptional co-regulation of genes implicated in P. tricornutum chloroplast and mitochondrial metabolism, as well as the functions of diverse transcription factors underpinning this co-regulation. The resource is publically available as PhaeoNet, an advanced tool to understand diatom gene co-regulation.},
keywords = {aureochromes, chloroplast-mitochondria, epigenetics, sigma factors, stramenopile, team 5, thesis, transcriptomics},
pubstate = {published},
tppubtype = {article}
}
@proceedings{pmid33506142,
title = {Radiation Therapy in a Perineal Squamous Cell Carcinoma in a Patient With Fanconi Anemia: A Case Report and Review of Literature},
author = {Tanguy Perennec and Stéphane Supiot and Marc-André Mahe and Juliette Podevin and Emmanuel Rio and Caroline Abadie},
doi = {10.1016/j.adro.2020.08.003},
issn = {2452-1094},
year  = {2020},
date = {2020-08-20},
journal = {Adv Radiat Oncol},
volume = {6},
number = {1},
pages = {100546},
keywords = {out_lab},
pubstate = {published},
tppubtype = {proceedings}
}
@article{oliver2020drug,
title = {Drug resistance in glioblastoma: are persisters the key to therapy?},
author = {Lisa Oliver and Lisenn Lalier and Céline Salaud and Dominique Heymann and Pierre François Cartron and François M Vallette},
doi = {10.20517/cdr.2020.29},
year  = {2020},
date = {2020-08-07},
urldate = {2020-01-01},
journal = {Cancer Drug Resistance},
volume = {3},
number = {3},
pages = {287--301},
abstract = {Glioblastoma (GBM) represents the main form of brain tumors in adults, and one of the most aggressive cancers overall. The treatment of GBM is a combination of surgery (when possible), chemotherapy (usually Temozolomide, TMZ) and radiotherapy (RT). However, despite this heavy treatment, GBM invariably recur and the median length of survival following diagnosis is 12 to 15 months, with less than 10% of people surviving longer than five years. GBM is extremely resistant to most treatments because of its heterogeneous nature, which is associated with extreme clonal plasticity and the presence of cancer stem cells, refractory to TMZ- and RT-induced cell death. In this review, we explore the mechanisms by which cancer cells, and especially GBM, can acquire resistance to treatment. We describe and discuss the concept of persister/tolerant cells that precede and/or accompany the acquisition of resistance. Persister/tolerant cells are cancer cells that are not eliminated by treatment(s) because of different mechanisms ranging from dormancy/quiescence to senescence. We discuss the possibility of targeting these mechanisms in new therapeutic regimen.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid32916600,
title = {N6-Adenosine Methylation of miRNA-200b-3p Influences Its Functionality and Is a Theranostic Tool},
author = {Joséphine Briand and Aurélien A Sérandour and Arulraj Nadaradjane and Gwenola Bougras-Cartron and Dominique Heymann and Benjamin Ory and François M Vallette and Pierre-François Cartron},
doi = {10.1016/j.omtn.2020.08.010},
issn = {2162-2531},
year  = {2020},
date = {2020-08-01},
urldate = {2020-08-01},
journal = {Mol Ther Nucleic Acids},
volume = {22},
pages = {72--83},
abstract = {MicroRNAs (miRNAs or miRs) play crucial roles in biological and pathological processes. Some miRNAs also appear as promising biomarkers and therapeutic tools. However, the epitranscriptomic regulation of miRNAs is not yet fully elucidated in all of their fields of application. We report that adenosine methylation of miR-200b-3p inhibits its repressive function toward its mRNA targets such as XIAP by blocking the formation of the miRNA/3' UTR duplex. Our data indicate that the adenosine methylation of miR-200b-3p is associated with the survival of glioblastoma patients. Collectively, our data support the idea that the adenosine methylation of miR-200b-3p can be used as a prodrug having a selective cytotoxicity against cancer cells (while being harmless to peripheral blood mononuclear cells [PBMCs], astrocytes, neurons, and hepatocytes).},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid32916600b,
title = {N6-Adenosine Methylation of miRNA-200b-3p Influences Its Functionality and Is a Theranostic Tool},
author = {Joséphine Briand and Aurélien A Sérandour and Arulraj Nadaradjane and Gwenola Bougras-Cartron and Dominique Heymann and Benjamin Ory and François M Vallette and Pierre-François Cartron},
doi = {10.1016/j.omtn.2020.08.010},
issn = {2162-2531},
year  = {2020},
date = {2020-08-01},
urldate = {2020-08-01},
journal = {Mol Ther Nucleic Acids},
volume = {22},
pages = {72--83},
abstract = {MicroRNAs (miRNAs or miRs) play crucial roles in biological and pathological processes. Some miRNAs also appear as promising biomarkers and therapeutic tools. However, the epitranscriptomic regulation of miRNAs is not yet fully elucidated in all of their fields of application. We report that adenosine methylation of miR-200b-3p inhibits its repressive function toward its mRNA targets such as XIAP by blocking the formation of the miRNA/3' UTR duplex. Our data indicate that the adenosine methylation of miR-200b-3p is associated with the survival of glioblastoma patients. Collectively, our data support the idea that the adenosine methylation of miR-200b-3p can be used as a prodrug having a selective cytotoxicity against cancer cells (while being harmless to peripheral blood mononuclear cells [PBMCs], astrocytes, neurons, and hepatocytes).},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{EQ5:GROISILLIER:2020,
title = {The genome of Ectocarpus subulatus - A highly stress-tolerant brown alga},
author = {Simon M Dittami and Erwan Corre and Loraine Brillet-Guéguen and Agnieszka P Lipinska and Noé Pontoizeau and Meziane Aite and Komlan Avia and Christophe Caron and Chung Hyun Cho and Jonas Collén and Alexandre Cormier and Ludovic Delage and Sylvie Doubleau and Clémence Frioux and Angélique Gobet and Irene González-Navarrete and Agnès Groisillier and Cécile Hervé and Didier Jollivet and Hetty KleinJan and Catherine Leblanc and Xi Liu and Dominique Marie and Gabriel V Markov and André E Minoche and Misharl Monsoor and Pierre Pericard and Marie-Mathilde Perrineau and Akira F Peters and Anne Siegel and Amandine Siméon and Camille Trottier and Hwan Su Yoon and Heinz Himmelbauer and Catherine Boyen and Thierry Tonon},
url = {http://www.sciencedirect.com/science/article/pii/S1874778720300015},
doi = {https://doi.org/10.1016/j.margen.2020.100740},
issn = {1874-7787},
year  = {2020},
date = {2020-08-01},
journal = {Marine Genomics},
volume = {52},
pages = {100740},
abstract = {Brown algae are multicellular photosynthetic stramenopiles that colonize marine rocky shores worldwide. Ectocarpus sp. Ec32 has been established as a genomic model for brown algae. Here we present the genome and metabolic network of the closely related species, Ectocarpus subulatus KÛtzing, which is characterized by high abiotic stress tolerance. Since their separation, both strains show new traces of viral sequences and the activity of large retrotransposons, which may also be related to the expansion of a family of chlorophyll-binding proteins. Further features suspected to contribute to stress tolerance include an expanded family of heat shock proteins, the reduction of genes involved in the production of halogenated defence compounds, and the presence of fewer cell wall polysaccharide-modifying enzymes. Overall, E. subulatus has mainly lost members of gene families down-regulated in low salinities, and conserved those that were up-regulated in the same condition. However, 96% of genes that differed between the two examined Ectocarpus species, as well as all genes under positive selection, were found to encode proteins of unknown function. This underlines the uniqueness of brown algal stress tolerance mechanisms as well as the significance of establishing E. subulatus as a comparative model for future functional studies.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid32622877,
title = {Bisphosphonates in common pediatric and adult bone sarcomas},
author = {Marie-Francoise Heymann and Frederic Lezot and Dominique Heymann},
doi = {10.1016/j.bone.2020.115523},
issn = {1873-2763},
year  = {2020},
date = {2020-07-03},
urldate = {2020-01-01},
journal = {Bone},
volume = {139},
pages = {115523},
abstract = {The therapeutic strategies proposed currently for bone sarcomas are based on neo-adjuvant chemotherapy, delayed en-bloc wide resection, and adjuvant chemotherapy. Unfortunately, bone sarcomas are characterized by high rates of poor drug response, with a high risk of drug resistance, local recurrence and/or a high propensity for induced metastases. The pathogenesis of bone sarcomas is strongly associated with dysregulation of local bone remodeling and increased osteolysis that plays a part in tumor development. In this context, bisphosphonates (BPs) have been proposed as a single agent or in combination with conventional drugs to block bone resorption and the vicious cycle established between bone and sarcoma cells. Pre-clinical in vitro studies revealed the potential "anti-tumor" activities of nitrogen-bisphosphonates (N-BPs). In pre-clinical models, N-BPs reduced significantly primary tumor growth in osteosarcoma and Ewing sarcoma, and the installation of lung metastases. In chondrosarcoma, N-BPs reduced the recurrence of local tumors after intralesional curettage, and increased overall survival. In pediatric and adult osteosarcoma patients, N-BPs have been assessed in combination with conventional chemotherapy and surgery in randomized phase 3 studies with no improvement in clinical outcome. The lack of benefit may potentially be explained by the biological impact of N-BPs on macrophage differentiation/recruitment which may alter CD8-T lymphocyte infiltration. Thanks to their considerable affinity for the mineralized extracellular matrix, BPs are an excellent platform for drug delivery in malignant bone sites with reduced systemic toxicity, which opens up new opportunities for their future use.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Carraro2020,
title = {An analog to digital converter controls bistable transfer competence development of a widespread bacterial integrative and conjugative element},
author = {Nicolas Carraro and Xavier Richard and Sandra Sulser and François Delavat and Christian Mazza and Jan Roelof van der Meer},
url = {hal-04202217v1 },
doi = {10.7554/eLife.57915},
issn = {2050084X},
year  = {2020},
date = {2020-07-01},
urldate = {2020-07-01},
journal = {eLife},
volume = {9},
pages = {1--40},
publisher = {eLife Sciences Publications Ltd},
abstract = {Conjugative transfer of the integrative and conjugative element ICEclc in Pseudomonas requires development of a transfer competence state in stationary phase, which arises only in 3-5% of individual cells. The mechanisms controlling this bistable switch between non-active and transfer competent cells have long remained enigmatic. Using a variety of genetic tools and epistasis experiments in P. putida, we uncovered an ‘upstream&#039; cascade of three consecutive transcription factor-nodes, which controls transfer competence initiation. One of the uncovered transcription factors (named BisR) is representative for a new regulator family. Initiation activates a feedback loop, controlled by a second hitherto unrecognized heteromeric transcription factor named BisDC. Stochastic modeling and experimental data demonstrated the feedback loop to act as a scalable converter of unimodal (population-wide or ‘analog&#039;) input to bistable (subpopulation-specific or ‘digital&#039;) output. The feedback loop further enables prolonged production of BisDC, which ensures expression of the ‘downstream&#039; functions mediating ICE transfer competence in activated cells. Phylogenetic analyses showed that the ICEclc regulatory constellation with BisR and BisDC is widespread among Gamma-and Beta-proteobacteria, including various pathogenic strains, highlighting its evolutionary conservation and prime importance to control the behaviour of this wide family of conjugative elements.},
keywords = {Adaptation, Bistability, Feedback control, Horizontal gene transfer, ICEclc, Pseudomonas putida, Regulation, Stochastic modeling, team 5},
pubstate = {published},
tppubtype = {article}
}
@article{pmid32292693,
title = {Adapting palliative radiation therapy for bone metastases during the Covid-19 pandemic: GEMO position paper},
author = {Sébastien Thureau and Jean Christophe Faivre and Richard Assaker and Emmanuel Biver and Cyrille B Confavreux and Françoise Debiais and Martine Duterque-Coquillaud and Francesco Giammarile and Dominique Heymann and Frédéric E Lecouvet and Laetitia Morardet and Frederic Paycha and Jean-Jacques Body and Marie-Hélène Vieillard},
doi = {10.1016/j.jbo.2020.100291},
issn = {2212-1366},
year  = {2020},
date = {2020-06-01},
urldate = {2020-06-01},
journal = {J Bone Oncol},
volume = {22},
pages = {100291},
abstract = {The current health crisis caused by COVID-19 is a challenge for oncology treatment, especially when it comes to radiotherapy. Cancer patients are already known to be very fragile and COVID-19 brings about the risk of severe respiratory complications. In order to treat patients safely while protecting medical teams, the entire health care system must optimize the way it approaches prevention and treatment at a time when social distancing is key to stemming this pandemic. All indications and treatment modalities must be re-discussed. This is particularly the case for radiotherapy of bone metastases for which it is possible to reduce the number of sessions, the frequency of transport and the complexity of treatments. These changes will have to be discussed according to the organization of each radiotherapy department and the health situation, while medical teams must remain vigilant about the risks of complications of bone metastases, particularly spinal metastases. In this short piece, the members of the GEMO (the European Study Group of Bone Metastases) offer a number of recommendations to achieve the above objectives, both in general and in relation to five of the most common situations on radiation therapy for bone metastases.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@patent{demeyer2020,
title = {Disulfonate stilbenes for use in the treatment of proliferative diseases},
author = {Fabrice Fleury and Alexandre Demeyer and Pierre Weigel and Benoit Chenais and Monique Mathé and Jacques Lebreton},
url = {https://worldwide.espacenet.com/patent/search/family/064564793/publication/WO2020104634A1?q=pn%3DWO2020104634A1},
year  = {2020},
date = {2020-05-28},
number = {WO2020104634A1},
abstract = {This invention relates to compounds of general formula: wherein R0A and R0B are independently selected from hydrogen and pharmaceutically acceptable cations; and RA and RB are identical and selected from amide, carbamate, sulphonamide, azido, cyano and halide. The invention also relates to a pharmaceutical composition comprising a compound according to the invention. According to an embodiment, the composition further comprises another active ingredient, especially an antineoplastic agent. The invention also relates to a compound or a composition according to the invention for use as a medicament, especially a compound or a composition for use in the treatment of a proliferative disease such as for example cancer.},
keywords = {team 3, thesis},
pubstate = {published},
tppubtype = {patent}
}
@article{Dhingra2020,
title = {Customised fragment libraries for ab initio protein structure prediction using a structural alphabet},
author = {Surbhi Dhingra and Ramanathan Sowdhamini and Yves-Henri Sanejouand and Frédéric Cadet and Bernard Offmann},
url = {https://arxiv.org/pdf/2005.01696.pdf},
year  = {2020},
date = {2020-05-01},
journal = {arXiv:2005.01696},
abstract = {Motivation: Computational protein structure prediction has taken over the structural community in past few decades, mostly focusing on the development of Template-Free modelling (TFM) or ab initio modelling protocols. Fragment-based assembly (FBA), falls under this category and is by far the most popular approach to solve the spatial arrangements of proteins. FBA approaches usually rely on sequence based profile comparison to generate fragments from a representative structural database. Here we report the use of Protein Blocks (PBs), a structural alphabet (SA) to perform such sequence comparison and to build customised fragment libraries for TFM. Results: We demonstrate that predicted PB sequences for a query protein can be used to search for high quality fragments that overall cover above 90% of the query. The fragments generated are of minimum length of 11 residues, and fragments that cover more than 30% of the query length were often obtained. Our work shows that PBs can serve as a good way to extract structurally similar fragments from a database of representatives of non-homologous structures and of the proteins that contain less ordered regions.},
keywords = {team 1, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1259/bjrcr.20190118,
title = {Report of a unique case of gemcitabine-induced radiation recall myelitis following spinal cord irradiation},
author = {Ingrid Masson and Stéphane Supiot and Isabelle Doutriaux-Dumoulin and François Thillays},
url = {https://doi.org/10.1259/bjrcr.20190118},
doi = {10.1259/bjrcr.20190118},
year  = {2020},
date = {2020-04-23},
urldate = {2020-04-23},
journal = {BJR|case reports},
volume = {6},
number = {3},
pages = {20190118},
abstract = {Radiation recall is a rare phenomenon, defined as an acute inflammatory reaction in a previously irradiated area, after administration of anti-tumor agents, including chemotherapy. It is most commonly reported to trigger skin reactions but internal organ involvement is possible, particularly with gemcitabine. We report here a unique case of a gemcitabine-induced radiation recall myelitis following spinal irradiation.A 53-year-old patient received analgesic irradiation of the seventh thoracic vertebra (T7) in the context of metastatic non-small cell lung cancer, at conventional radiotherapy dose and fractionation. She was subsequently treated with gemcitabine and developed myelitis whose chronology is compatible with a radiation recall reaction. Spinal MRI confirmed a T6–T7 spinal cord enhancement, with an associated spinal cord oedema. Corticosteroids and supportive care did not improve myelitis symptoms. The patient died within a year of the radiation recall, due to a metastatic progression of lung cancer.This is, to our knowledge, the first reported case of gemcitabine-induced radiation recall myelitis and only the third case involving the spinal cord. Radiation recall is a rare and poorly understood phenomenon and all cases should be reported.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid32267172,
title = {Radiotherapy-induced overexpression of exosomal miRNA-378a-3p in cancer cells limits natural killer cells cytotoxicity},
author = {Joséphine Briand and Delphine Garnier and Arulraj Nadaradjane and Karen Clément-Colmou and Vincent Potiron and Stéphane Supiot and Gwenola Bougras-Cartron and Jean-Sébastien Frenel and Dominique Heymann and François M Vallette and Pierre-François Cartron},
doi = {10.2217/epi-2019-0193},
issn = {1750-192X},
year  = {2020},
date = {2020-04-08},
urldate = {2020-01-01},
journal = {Epigenomics},
volume = {12},
number = {5},
pages = {397--408},
abstract = { We here hypothesized that tumor-derived exosomal miRNA (TexomiR) released from irradiated tumors may play a role in the tumor cells escape to natural killer (NK) cells.  Our study included the use of different cancer cell lines, blood biopsies of xenograph mice model and patients treated with radiotherapy.  The irradiation of cancer cells promotes the TET2-mediated demethylation of miR-378 promoter, miR-378a-3p overexpression and its loading in exosomes, inducing the decrease of granzyme-B (GZMB) secretion by NK cells. An inverse correlation between TexomiR-378a-3p and GZMB was observed in murine and human blood samples.  Our work identifies TexomiR-378a-3p as a molecular signature associated with the loss of NK cells cytotoxicity via the decrease of GZMB expression upon radiotherapy.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{heymann2020centre,
title = {Centre de ressources Biologiques-Tumorothèque: bioresources and associated clinical data dedicated to translational research in oncology at the institut de cancérologie de l’Ouest, France},
author = {Dominique Heymann and Estelle Verhille and Vanessa Veron and Marie Vitre and Florian Delmas and Cécile Henry and Yann Gouy and Marie Amiand and Jean-Marie Bard},
doi = {10.5334/ojb.62},
year  = {2020},
date = {2020-04-07},
urldate = {2020-01-01},
journal = {Open Journal of Bioresources},
volume = {7},
pages = {5},
abstract = {The Centre de Ressources Biologiques-Tumorothèque ICO is a biobank integrated in a clinical cancer center (ICO, Institut de Cancérologie de l’Ouest, Saint-Herblain, FR) that collects tissues (snap frozen, FFPE, TMA) and biological (serum, plasma, DNA, RNA, stools, etc) samples from oncology patients and dedicated to translational research. The biobank started its activities in 2002 and is certified NF S 96 900. Activities are framed by a quality management system with established and validated SOPs for all work procedures. Samples stored into the biobank are available for both academic as well as commercial researchers, through a defined access procedure. Currently the bioresources consist in more than 99.500 samples with informed consent and associated clinical data.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@inbook{cEQ3:ayadi_FLEURY:2020,
title = {Comparative Advantages and Limitations of Quantum Dots in Protein Array Applications},
author = {Nizar Ayadi and Florian Lafont and Cathy Charlier and Houda Benhelli-Mokrani and Pavel Sokolov and Alyona Sukhanova and Fabrice Fleury and Igor Nabiev},
year  = {2020},
date = {2020-04-01},
booktitle = {Quantum Dots},
volume = {2135},
pages = {259--273},
publisher = {Springer},
address = {New York, NY},
edition = {Humana},
series = {Methods in Molecular Biology},
keywords = {impact, team 3, thesis},
pubstate = {published},
tppubtype = {inbook}
}
@inbook{cEQ5:ZHAO_TIRICHINE:2020,
title = {Epigenetic control of diatom genomes: An overview from in Silico characterisation to functional studies},
author = {Xue Zhao and Antoine Hoguin and Timothée Chaumier and Leila Tirichine},
year  = {2020},
date = {2020-04-01},
booktitle = {The molecular life of diatoms},
publisher = {Springer Nature Switzerland AG},
keywords = {team 5, thesis},
pubstate = {published},
tppubtype = {inbook}
}
@article{pmid32218136,
title = {Primary Retention of Molars and RANKL Signaling Alteration during Craniofacial Growth},
author = {Andrea Gama and Laura Maman and Jorge William Vargas-Franco and Rana Omar and Bénédicte Brounais-Le Royer and Hideo Yagita and Sylvie Babajko and Ariane Berdal and Ana Carolina Acevedo and Dominique Heymann and Frédéric Lézot and Beatriz Castaneda},
doi = {10.3390/jcm9040898},
issn = {2077-0383},
year  = {2020},
date = {2020-03-25},
urldate = {2020-03-01},
journal = {J Clin Med},
volume = {9},
number = {4},
abstract = {The primary retention of molars observed in clinic corresponds to a still-unexplained absence of molar eruption despite the presence of an eruption pathway, resembling the experimental transient inhibition of RANKL signaling in mice. The aim of the present study was to confront the hypothesis according to which the primary retention of molars is associated with transitory perturbations to RANKL signaling during growth as part of a wider craniofacial skeleton pattern. The experimental strategy was based on combining a clinical study and an animal study corresponding to the characterization of the craniofacial phenotypes of patients with primary retention of molars and analyses in mice of the consequences of transient inhibition of RANKL signaling on molar eruption and craniofacial growth. The clinical study validated the existence of a particular craniofacial phenotype in patients with primary retention of molars: a retromandibular skeletal class II typology with reduced mandibular dimensions which manifests itself at the dental level by a class II/2 with palatoversion of the upper incisors and anterior overbite. The animal study demonstrated that transient invalidation of RANKL signaling had an impact on the molar eruption process, the severity of which was dependent on the period of inhibition and was associated with a reduction in two craniofacial morphometric parameters: total skull length and craniofacial vault length. In conclusion, primary retention of molars may be proposed as part of the craniofacial skeleton phenotype associated with a transitory alteration in RANKL signaling during growth.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid32209985,
title = {Origins of Alterations to  Null Mutant Mouse Dental Root Development},
author = {Andrea Gama and Jorge William Vargas-Franco and Diana Carolina Sánchez Mesa and Elizabeth Restrepo Bedoya and Jérome Amiaud and Sylvie Babajko and Ariane Berdal and Ana Carolina Acevedo and Dominique Heymann and Frédéric Lézot and Beatriz Castaneda},
doi = {10.3390/ijms21062201},
issn = {1422-0067},
year  = {2020},
date = {2020-03-23},
urldate = {2020-03-01},
journal = {Int J Mol Sci},
volume = {21},
number = {6},
abstract = {The purpose of the present study was to assess the early stages of development of mouse first molar roots in the osteopetrotic context of RANKL invalidation in order to demonstrate that the radicular phenotype observed resulted not only from defective osteoclasts, but also from loss of cell-to-cell communication among dental, periodontium and alveolar bone cells involving RANKL signaling. Two experimental models were used in this study:  mutants with permanent RANKL invalidation, and C57BL/6J mice injected during the first postnatal week with a RANKL neutralizing antibody corresponding to a transient RANKL invalidation. The dento-alveolar complex was systematically analyzed using micro-CT, and histological and immunohistochemical approaches. These experiments showed that the root elongation alterations observed in the  mice were associated with reduced proliferation of the RANK-expressing HERS cells with a significant decrease in proliferating cell nuclear antigen (PCNA) expression and a significant increase in P21 expression. The phenotypic comparison of the adult first molar root at 35 days between permanent and transitory invalidations of RANKL made it possible to demonstrate that alterations in dental root development have at least two origins, one intrinsic and linked to proliferation/differentiation perturbations in dental-root-forming cells, the other extrinsic and corresponding to disturbances of bone cell differentiation/function.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid32293453,
title = {microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation},
author = {Maureen Labbé and Christianne Hoey and Jessica Ray and Vincent Potiron and Stéphane Supiot and Stanley K Liu and Delphine Fradin},
doi = {10.1186/s12943-020-01186-6},
issn = {1476-4598},
year  = {2020},
date = {2020-03-23},
urldate = {2020-01-01},
journal = {Mol Cancer},
volume = {19},
number = {1},
pages = {63},
abstract = {As the most frequently diagnosed non-skin cancer in men and a leading cause of cancer-related death, understanding the molecular mechanisms that drive treatment resistance in prostate cancer poses a significant clinical need. Radiotherapy is one of the most widely used treatments for prostate cancer, along with surgery, hormone therapy, and chemotherapy. However, inherent radioresistance of tumor cells can reduce local control and ultimately lead to poor patient outcomes, such as recurrence, metastasis and death. The underlying mechanisms of radioresistance have not been fully elucidated, but it has been suggested that miRNAs play a critical role. miRNAs are small non-coding RNAs that regulate gene expression in every signaling pathway of the cell, with one miRNA often having multiple targets. By fine-tuning gene expression, miRNAs are important players in modulating DNA damage response, cell death, tumor aggression and the tumor microenvironment, and can ultimately affect a tumor's response to radiotherapy. Furthermore, much interest has focused on miRNAs found in biofluids and their potential utility in various clinical applications. In this review, we summarize the current knowledge on miRNA deregulation after irradiation and the associated functional outcomes, with a focus on prostate cancer. In addition, we discuss the utility of circulating miRNAs as non-invasive biomarkers to diagnose, predict response to treatment, and prognosticate patient outcomes.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Yaremenko2020b,
title = {Synthetic Peroxides Promote Apoptosis of Cancer Cells by Inhibiting P-Glycoprotein ABCB5},
author = {Ivan A Yaremenko and Paolo Coghi and Parichat Prommana and Congling Qiu and Peter S Radulov and Yuanqing Qu and Yulia Yu Belyakova and Enrico Zanforlin and Vladimir A Kokorekin and Yuki Yu Jun Wu and Fabrice Fleury and Chairat Uthaipibull and Vincent Kam Wai Wong and Alexander O Terent'ev},
doi = {10.1002/cmdc.202000042},
issn = {18607187},
year  = {2020},
date = {2020-03-10},
journal = {ChemMedChem},
volume = {15},
number = {13},
pages = {1118--1127},
abstract = {This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells: in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5‐tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively).
In some instances, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin and artenusic acid.
Annexin V flow‐cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P‐glycoprotein (P‐gp/ABCB5)‐overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug‐resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine‐sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC50=5.81 vs 65.18 μm). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug‐resistant hepatocellular carcinoma.},
keywords = {apoptosis, cancer, cytotoxicity, HepG2, malaria, ozonide, Peroxides, team 3, tetraoxane},
pubstate = {published},
tppubtype = {article}
}
@article{pmid32151797,
title = {TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model},
author = {Brice Moukengue and Hannah K Brown and Céline Charrier and Séverine Battaglia and Marc Baud'huin and Thibaut Quillard and Therese M Pham and Ioannis S Pateras and Vassilis G Gorgoulis and Thomas Helleday and Dominique Heymann and Ulrika Warpman Berglund and Benjamin Ory and Francois Lamoureux},
doi = {10.1016/j.ebiom.2020.102704},
issn = {2352-3964},
year  = {2020},
date = {2020-03-07},
urldate = {2020-03-07},
journal = {EBioMedicine},
volume = {53},
pages = {102704},
abstract = {BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumour. Unfortunately, no new treatments are approved and over the last 30 years the survival rate remains only 30% at 5 years for poor responders justifying an urgent need of new therapies. The Mutt homolog 1 (MTH1) enzyme prevents incorporation of oxidized nucleotides into DNA and recently developed MTH1 inhibitors may offer therapeutic potential as MTH1 is overexpressed in various cancers.

METHODS: The aim of this study was to evaluate the therapeutic benefits of targeting MTH1 with two chemical inhibitors, TH588 and TH1579 on human osteosarcoma cells. Preclinical efficacy of TH1579 was assessed in human osteosarcoma xenograft model on tumour growth and development of pulmonary metastases.

FINDINGS: MTH1 is overexpressed in OS patients and tumour cell lines, compared to mesenchymal stem cells. In vitro, chemical inhibition of MTH1 by TH588 and TH1579 decreases OS cells viability, impairs their cell cycle and increases apoptosis in OS cells. TH1579 was confirmed to bind MTH1 by CETSA in OS model. Moreover, 90 mg/kg of TH1579 reduces in vivo tumour growth by 80.5% compared to non-treated group at day 48. This result was associated with the increase in 8-oxo-dG integration into tumour cells DNA and the increase of apoptosis. Additionally, TH1579 also reduces the number of pulmonary metastases.

INTERPRETATION: All these results strongly provide a pre-clinical proof-of-principle that TH1579 could be a therapeutic option for patients with osteosarcoma.

FUNDING: This study was supported by La Ligue Contre le Cancer, la SFCE and Enfants Cancers Santé.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Dussouy2020,
title = {Linear triazole-linked pseudo oligogalactosides as scaffolds for galectin inhibitor development.},
author = {Christophe Dussouy and Chandan Kishor and Annie Lambert and Clément Lamoureux and Helen Blanchard and Cyrille Grandjean},
doi = {10.1111/cbdd.13683},
issn = {1747-0285 (Electronic)},
year  = {2020},
date = {2020-03-01},
journal = {Chemical biology & drug design},
abstract = {Galectins play key roles in numerous biological processes. Their mode of action depends on their localization which can be extracellular, cytoplasmic or nuclear, and is partly mediated through interactions with β-galactose containing glycans. Galectins have emerged as novel therapeutic targets notably for the treatment of inflammatory disorders and cancers. This has stimulated the design of carbohydrate-based inhibitors targeting the carbohydrate recognition domains (CRDs) of the galectins. Pursuing this approach, we reasoned that linear oligo-galactosides obtained by straightforward iterative click-chemistry could mimic poly-lactosamine motifs expressed at eukaryote cell surfaces which the extracellular form of galectin-3, a prominent member of the galectin family, specifically recognizes. Affinities towards galectin-3 consistently increased with the length of the representative oligogalactosides but without reaching that of oligo-lactosamines. Elucidation of the X-ray crystal structures of the galectin-3 CRD in complex with a synthesized di- and tri-galactoside confirmed that the compounds bind within the carbohydrate-binding site. The atomic structures revealed that binding interactions mainly occur with the galactose moiety at the non-reducing end, primarily with subsites C and D of the CRD, differing from oligo-lactosamine which bind more consistently across the whole groove formed by the five subsites (A-E) of the galectin-3 CRD.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{Aganyants2020,
title = {Rational engineering of the substrate specificity of a thermostable d-hydantoinase (Dihydropyrimidinase)},
author = {Hovsep Aganyants and Pierre Weigel and Yeranuhi Hovhannisyan and Michèle Lecocq and Haykanush Koloyan and Artur Hambardzumyan and Anichka Hovsepyan and Jean Noël Hallet and Vehary Sakanyan},
doi = {10.3390/ht9010005},
issn = {25715135},
year  = {2020},
date = {2020-03-01},
journal = {High-Throughput},
volume = {9},
number = {1},
publisher = {MDPI AG},
abstract = {D-hydantoinases catalyze an enantioselective opening of 5-and 6-membered cyclic structures and therefore can be used for the production of optically pure precursors for biomedical applications. The thermostable D-hydantoinase from Geobacillus stearothermophilus ATCC 31783 is a manganese-dependent enzyme and exhibits low activity towards bulky hydantoin derivatives. Homology modeling with a known 3D structure (PDB code: 1K1D) allowed us to identify the amino acids to be mutated at the substrate binding site and in its immediate vicinity to modulate the substrate specificity. Both single and double substituted mutants were generated by site-directed mutagenesis at appropriate sites located inside and outside of the stereochemistry gate loops (SGL) involved in the substrate binding. Substrate specificity and kinetic constant data demonstrate that the replacement of Phe159 and Trp287 with alanine leads to an increase in the enzyme activity towards D,L-5-benzyl and D,L-5-indolylmethyl hydantoins. The length of the side chain and the hydrophobicity of substrates are essential parameters to consider when designing the substrate binding pocket for bulky hydantoins. Our data highlight that D-hydantoinase is the authentic dihydropyrimidinase involved in the pyrimidine reductive catabolic pathway in moderate thermophiles.},
keywords = {Biocatalyst, D-hydantoinase, Dihydropyrimidinase, Long inverse PCR, Manganese-dependence, Site-directed mutagenesis, Substrate specificity, team 3, Thermophilic bacteria},
pubstate = {published},
tppubtype = {article}
}
@article{EQ2:LAMBERT:2020,
title = {Glutathione Deficiency in Sinorhizobium meliloti Does Not Impair Bacteroid Differentiation But Induces Early Senescence in the Interaction With Medicago truncatula},
author = {Li Yang and Sarra El Msehli and Sofiane Benyamina and Annie Lambert and Julie Hopkins and Julie Cazareth and Olivier Pierre and Didier Hérouart and Samira Achi-Smiti and Eric Boncompagni and Pierre Frendo},
url = {https://doi.org/10.3389%2Ffpls.2020.00137},
doi = {10.3389/fpls.2020.00137},
year  = {2020},
date = {2020-03-01},
journal = {Frontiers in Plant Science},
volume = {11},
publisher = {Frontiers Media SA},
abstract = {Under nitrogen-limiting conditions, legumes are able to interact symbiotically with bacteria of the Rhizobiaceae family. This interaction gives rise to a new organ, named a root nodule. Root nodules are characterized by an increased glutathione (GSH) and homoglutathione (hGSH) content compared to roots. These low molecular thiols are very important in the biological nitrogen fixation. In order to characterize the modification of nodule activity induced by the microsymbiont glutathione deficiency, physiological, biochemical, and gene expression modifications were analyzed in nodules after the inoculation of Medicago truncatula with the SmgshB mutant of Sinorhizobium meliloti which is deficient in GSH production. The decline in nitrogen fixation efficiency was correlated to the reduction in plant shoot biomass. Flow cytometry analysis showed that SmgshB bacteroids present a higher DNA content than free living bacteria. Live/dead microscopic analysis showed an early bacteroid degradation in SmgshB nodules compared to control nodules which is correlated to a lower bacteroid content at 20 dpi. Finally, the expression of two marker genes involved in nitrogen fixation metabolism, Leghemoglobin and Nodule Cysteine Rich Peptide 001, decreased significantly in mutant nodules at 20 dpi. In contrast, the expression of two marker genes involved in the nodule senescence, Cysteine Protease 6 and Purple Acid Protease, increased significantly in mutant nodules at 10 dpi strengthening the idea that an early senescence process occurs in SmgshB nodules. In conclusion, our results showed that bacterial GSH deficiency does not impair bacterial differentiation but induces an early nodule senescence.
},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid32098627,
title = {Cytosine methylation of mature microRNAs inhibits their functions and is associated with poor prognosis in glioblastoma multiforme},
author = {Mathilde Cheray and Amandine Etcheverry and Camille Jacques and Romain Pacaud and Gwenola Bougras-Cartron and Marc Aubry and Florent Denoual and Pierre Peterlongo and Arulraj Nadaradjane and Joséphine Briand and Farida Akcha and Dominique Heymann and François M Vallette and Jean Mosser and Benjamin Ory and Pierre-François Cartron},
doi = {10.1186/s12943-020-01155-z},
issn = {1476-4598},
year  = {2020},
date = {2020-02-25},
urldate = {2020-01-01},
journal = {Mol Cancer},
volume = {19},
number = {1},
pages = {36},
abstract = {BACKGROUND: Literature reports that mature microRNA (miRNA) can be methylated at adenosine, guanosine and cytosine. However, the molecular mechanisms involved in cytosine methylation of miRNAs have not yet been fully elucidated. Here we investigated the biological role and underlying mechanism of cytosine methylation in miRNAs in glioblastoma multiforme (GBM).

METHODS: RNA immunoprecipitation with the anti-5methylcytosine (5mC) antibody followed by Array, ELISA, dot blot, incorporation of a radio-labelled methyl group in miRNA, and miRNA bisulfite sequencing were perfomred to detect the cytosine methylation in mature miRNA. Cross-Linking immunoprecipiation qPCR, transfection with methylation/unmethylated mimic miRNA, luciferase promoter reporter plasmid, Biotin-tagged 3'UTR/mRNA or miRNA experiments and in vivo assays were used to investigate the role of methylated miRNAs. Finally, the prognostic value of methylated miRNAs was analyzed in a cohorte of GBM pateints.

RESULTS: Our study reveals that a significant fraction of miRNAs contains 5mC. Cellular experiments show that DNMT3A/AGO4 methylated miRNAs at cytosine residues inhibit the formation of miRNA/mRNA duplex and leading to the loss of their repressive function towards gene expression. In vivo experiments show that cytosine-methylation of miRNA abolishes the tumor suppressor function of miRNA-181a-5p miRNA for example. Our study also reveals that cytosine-methylation of miRNA-181a-5p results is associated a poor prognosis in GBM patients.

CONCLUSION: Together, our results indicate that the DNMT3A/AGO4-mediated cytosine methylation of miRNA negatively.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Belcour2020,
title = {Inferring Biochemical Reactions and Metabolite Structures to Understand Metabolic Pathway Drift},
author = {Arnaud Belcour and Jean Girard and Méziane Aite and Ludovic Delage and Camille Trottier and Charlotte Marteau and Cédric Leroux and Simon M Dittami and Pierre Sauleau and Erwan Corre and Jacques Nicolas and Catherine Boyen and Catherine Leblanc and Jonas Collén and Anne Siegel and Gabriel V Markov},
url = {https://www.sciencedirect.com/science/article/pii/S2589004220300328},
doi = {10.1016/J.ISCI.2020.100849},
issn = {2589-0042},
year  = {2020},
date = {2020-02-01},
journal = {iScience},
volume = {23},
number = {2},
pages = {100849},
publisher = {Elsevier},
abstract = {Inferring genome-scale metabolic networks in emerging model organisms is challenged by incomplete biochemical knowledge and partial conservation of biochemical pathways during evolution. Therefore, specific bioinformatic tools are necessary to infer biochemical reactions and metabolic structures that can be checked experimentally. Using an integrative approach combining genomic and metabolomic data in the red algal model Chondrus crispus, we show that, even metabolic pathways considered as conserved, like sterols or mycosporine-like amino acid synthesis pathways, undergo substantial turnover. This phenomenon, here formally defined as “metabolic pathway drift,” is consistent with findings from other areas of evolutionary biology, indicating that a given phenotype can be conserved even if the underlying molecular mechanisms are changing. We present a proof of concept with a methodological approach to formalize the logical reasoning necessary to infer reactions and molecular structures, abstracting molecular transformations based on previous biochemical knowledge.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid31916450,
title = {Cell-free circulating epimarks in cancer monitoring},
author = {Manon Duforestel and Joséphine Briand and Gwenola Bougras-Cartron and Dominique Heymann and Jean-Sébastien Frenel and François M Vallette and Pierre-François Cartron},
doi = {10.2217/epi-2019-0170},
issn = {1750-192X},
year  = {2020},
date = {2020-01-09},
urldate = {2020-01-01},
journal = {Epigenomics},
volume = {12},
number = {2},
pages = {145--155},
abstract = {Cancer numbers increasing, cases heterogeneity and the drug resistance emergence have pushed scientists to search for innovative solutions for patients and epimutations can be one. Methylated DNA, modified nucleosomes and noncoding RNAs are found in all cells, including tumor cells. They are intracellular actors but also have intercellular communication roles, being released in extracellular environment and in different body fluids. Here, we reviewed current literature on the use of these blood circulating epimarks in cancer monitoring. What stands out is that epimarkers must be considered as 'real time' images of the tumor, and can be isolated without invasive methods. In the future, the real challenge lies in the development of specific, sensitive, fast and clinically applicable detection and analysis methods of epimarkers.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{martinet2020performances,
title = {Performances of the Lamb Model to Describe the Vibrations of Gold Quantum-Sized Clusters},
author = {Quentin Martinet and Alice Berthelot and Adrien Girard and Baira Donoeva and Clothilde Comby-Zerbino and {É}lodie Romeo and Franck Bertorelle and Marte van der Linden and Nathalie Tarrat and Nicolas Combe and others},
doi = {10.1021/acs.jpcc.0c04722},
year  = {2020},
date = {2020-01-01},
journal = {The Journal of Physical Chemistry C},
volume = {124},
number = {35},
pages = {19324--19332},
publisher = {ACS Publications},
abstract = {Lamb modes describe the vibrations of an object as a whole from the stellar scale to the nanometer one. Lamb description has been built from the linear elasticity theory and considers a homogeneous elastic sphere. Our work tries to determine the minimum scale where this description remains valid by studying the vibration of quantum-sized gold clusters (Au6, Au9, and Au25) stabilized by organic molecules. First, our work shows that experimental frequencies of small-functionalized gold clusters obtained by low-frequency Raman spectroscopy can be interpreted with density functional theory calculations. Moreover, the Lamb model broadly succeeds in predicting these Raman acoustic modes only if a correction considering the mass of the surrounding ligands is added. Ligands affect vibrational modes of the core by their mass but also by their covalent bond with the core. The unexpected consequence of this electronic stabilization by the ligands is the sustainability of the Lamb description for clusters as small as six atoms. Finally, the limit of the Lamb model can be reached out at low temperature where the vibration mode spectrum presents a substructuration that the Lamb description, developed for a homogeneous sphere, is unable to predict.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1200/JCO.2020.38.6_suppl.93,
title = {Oligopelvis-GETUG P07: A multicenter phase II trial of combined salvage radiotherapy and hormone therapy in oligorecurrent pelvic node relapses of prostate cancer.},
author = {Stephane Supiot and David Pasquier and Xavier Buthaud and Nicolas Magné and Veronique Beckendorf and Paul Sargos and Gilles Crehange and Pascal Pommier and Genevieve Loos and Ali Hasbini and Igor Latorzeff and Marlon Silva and Fabrice Denis and Jean-Leon Lagrange and Loic Campion and Loig Vaugier and Audrey Blanc-Lapierre},
url = {https://doi.org/10.1200/JCO.2020.38.6_suppl.93},
doi = {10.1200/JCO.2020.38.6_suppl.93},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Journal of Clinical Oncology},
volume = {38},
number = {6_suppl},
pages = {93-93},
abstract = {Background: Oligorecurrent pelvic nodal relapse of prostatic cancer is a challenge for regional salvage treatments. We conducted OLIGOPELVIS – GETUG P07, a phase II trial of combined salvage radiotherapy and hormone therapy in oligorecurrent pelvic node relapses of prostate cancer (NCT02274779). Methods: OLIGOPELVIS–GETUG P07 was a prospective multi-center phase II trial investigating high-dose salvage pelvic irradiation with an additional dose to the fluorocholine-based positron-emission-tomography (FCH- PET)-positive pelvic lymph nodes (PLN), combined with six-month androgen blockade (LH-RH agonist or antagonist injections). The prescribed dose was 54 Gy in 1.8 Gy fractions with up to 66 Gy in 2.2 Gy fractions to the pathological PLN. Toxicity (CTCAE v4) and complete response rates (PSA &lt; 0.20 ng/ml) were analyzed. The main objective was to assess biochemical-clinical failure defined by a cluster of events including PSA progression (≥25 % and ≥ 2 ng/ml above the nadir) or clinical evidence of local or metastatic progression or post- treatment initiation of hormonal therapy or prostate cancer-related death. We hypothesized that salvage treatment would achieve a 2-year relapse-free survival of 70 %. Results: Seventy-four patients were recruited in fifteen French radiation oncology departments between August 2014 and July 2016. Seven were excluded before treatment because of violation of the inclusion criteria. The intention-to-treat analysis therefore included sixty-seven patients. Half of them had received prior prostatic/prostate bed irradiation. Median age was 67.7. Grade 2+ two-year urinary and intestinal toxicity were 10% and 2% respectively. At 2 and 3 years, 73.1 and 45.9% of patients achieved a persisting complete response respectively. After a median follow-up of 34 months, the 2-year progression-free survival rate was 77.6%. Median progression-free survival was 40.1 months. Conclusions: Combined pelvic salvage radiotherapy and hormone therapy allowed for prolonged tumor control in oligorecurrent pelvic node relapses of prostate cancer with limited toxicity. Clinical trial information: NCT02274779.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1200/JCO.2020.38.6_suppl.331,
title = {Late toxicity and quality of life from GETUG-AFU 22 study.},
author = {Igor Latorzeff and Stephane Guerif and Sandra Pelissier and Emmanuel Meyer and Julien Fraisse and Stephane Supiot and Gilles Crehange and Edouard Lagneau and Philippe Ronchin and Ahmed Benyoucef and Ali Hasbini and Pascal Pommier and Guy De Laroche and Laurent Salomon and Paul Sargos},
url = {https://doi.org/10.1200/JCO.2020.38.6_suppl.331},
doi = {10.1200/JCO.2020.38.6_suppl.331},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Journal of Clinical Oncology},
volume = {38},
number = {6_suppl},
pages = {331-331},
abstract = {331Background: Radical prostatectomy (RP) is recommended as a standard treatment for localized prostate cancer. However no recommendations exist for pts with immediate detectable PSA after RP. Methods: Pts with localized prostate cancer, treated by RP (R0 or R1), with a PSA level post-RP ≥0.2 ng/mL and ≤2 ng/mL at randomization and N0 M0 on imaging were included. Pts were randomized (1:1) to radiotherapy (RT) alone (RT arm) or 6 months degarelix hormone therapy (HT) with RT (RT+HT arm). RT consisted of pelvic irradiation (46 Gy in 23 Fr) with a boost on the prostate bed (66 Gy in 33 Fr). The primary endpoint was event-free survival (EFS). Acute and late toxicities were evaluated as secondary endpoints and scored using CTCAE V4.0 scale. Quality of life (QOL) was assessed with QLQ-C30 and QLQ-PR25 questionnaires at 12 and 24 months. Late toxicity was reported at 24 months. Results: From Jan-2013 to Sept-2015, 125 pts were included (RT arm: 64 pts; RT+HT arm: 61). Median follow up is 38 months (31.4; 44). The baseline characteristics are well-balanced between two arms: median age was 66 yrs (50-77), all men having an ECOG ≤1 (ECOG 0 in 92%), a median Gleason score of 7 (3-9), a median PSA of 0.3 ng/mL (0.09-1.82) post-RP and 0.6 ng/mL (0.12-3.65) at randomization. All pts received 33 Fr of RT. In the RT+HT arm 98.4% of pts received the 6 months of HT planned. All pts were eligible for safety analysis. At 24 months, no difference in late genitourinary (GU) or gastrointestinal (GI)toxicity was observed between the two arms (p=0.145) Grade 3 late toxicities were reported for 15/125 pts (12%): 8/64 pts (6.5%) in the RT arm and 7/61 pts (5.5%) in RT+HT arm (NS) and no toxicity grade &gt;3 was observed. Evaluation of QOL was assessable at 12 and 24 months of FU for 80%/89% pts and 59%/77% pts in RT/RT-HT arms respectively. At 12 months QLQ-PR25 HT related symptoms was significantly more important in the RT-HT arm (p=0.04). At 24 months no significant difference in QLQC-30 or QLQ-PR25 analysis was reported. Conclusions:, At 24 months in this phase II trial no significant difference in GI/GU toxicity and.QOL was observed between the two arms. GETUG-AFU 22 efficacy analysis is still pending. Clinical trial information: NCT01994239.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{cancers12030635,
title = {Can Comprehensive Geriatric Assessment Predict Tolerance of Radiotherapy for Localized Prostate Cancer in Men Aged 75 Years or Older?},
author = {Aurore Goineau and Loïc Campion and Jean-Marie Commer and Brigitte Vié and Agnès Ghesquière and Guillaume Béra and Didier Jaffres and Nicolas Magné and Xavier Artignan and Jérôme Chamois and Philippe Bergerot and Gilles Créhange and Elisabeth Deniaud-Alexandre and Xavier Buthaud and Yazid Belkacémi and Mélanie Doré and Laure De Decker and Stéphane Supiot},
url = {https://www.mdpi.com/2072-6694/12/3/635},
doi = {10.3390/cancers12030635},
issn = {2072-6694},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Cancers},
volume = {12},
number = {3},
abstract = {Curative radiotherapy for prostate cancer is common in the elderly. However, concerns about potential toxicity have inhibited access to radiotherapy for this population, for whom preserving quality of life (QoL) is crucial. The primary endpoint was to identify predictors of impaired QoL in men aged 75 years or older treated with curative intent radiotherapy with or without androgen deprivation therapy (ADT) for localized prostate cancer. We prospectively performed comprehensive geriatric assessment (CGA) and administered QoL questionnaires to 208 elderly (&gt;75 years) patients prior to, plus two and six months after, radiotherapy (NCT 02876237). The median age of the patients was 77 years (range 75-89). At the start of the study, comorbidities were highlighted in 65% of patients: 23% were depressed, 23% had cognitive impairment, and 16% had reduced independence. At six months, 9% of patients had a consistently decreased QoL (&gt;20 points), and a further 16% had a more moderate reduction (10 to 20 points) in QoL. None of the parameters studied (tumor characteristic, treatment, or oncogeriatric parameters) were predictive of a reduced QoL following radiotherapy. Though co-existing geriatric impairment was common, QoL was maintained for 75% of patients six months after radiotherapy. CGA was poorly predictive of tolerance of prostatic radiotherapy. Geriatric assessments dedicated to quality of life following radiotherapy need to be developed.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{LATORZEFF2020143,
title = {Indications et perspectives de l’hormonoradiothérapie des cancers de prostate à haut risque},
author = {I Latorzeff and P Sargos and G Créhange and Y Belkacémi and D Azria and A Hasbini and T Dubergé and A Toledano and P Graff-Cailleaud and O Chapet and C Hennequin and R Crevoisier and S Supiot and D Pasquier},
url = {https://www.sciencedirect.com/science/article/pii/S1278321820300160},
doi = {https://doi.org/10.1016/j.canrad.2019.06.018},
issn = {1278-3218},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Cancer/Radiothérapie},
volume = {24},
number = {2},
pages = {143-152},
abstract = {Résumé 
Le cancer de la prostate est un adénocarcinome sensible, dans plus de 80 % des cas, à la castration chimique, en raison de son hormonodépendance. Le cancer localement évolué et/ou à haut risque est défini en fonction du stade clinique, de la valeur initiale de la concentration sérique d’antigène spécifique de la prostate ou du score de Gleason élevé. L’hormonothérapie associée à la radiothérapie est le standard de la prise en charge et améliore le contrôle local, diminue le risque de métastase à distance et améliore les probabilités de survie spécifique et globale. La durée d’hormonothérapie, le niveau de dose de radiothérapie seule ou associée à la curiethérapie sont des données controversées dans la littérature. Le choix thérapeutique, pluridisciplinaire, dépend de l’âge et des maladies associées du patient, des critères pronostiques de la pathologie et de la fonction urinaire du patient. La recherche actuelle est orientée sur l’optimisation du contrôle local et à distance de ces formes agressives et intègre la chimiothérapie néoadjuvante ou adjuvante de même que les nouvelles hormonothérapies. 
Prostate cancer is a sensitive adenocarcinoma, in more than 80% of cases, to chemical castration, due to its hormone dependence. Locally advanced and/or high-risk cancer is defined based on clinical stage, initial prostate specific antigen serum concentration value or high Gleason score. Hormone therapy associated with radiation therapy is the standard of management and improves local control, reduces the risk of distant metastasis and improves specific and overall survival. Duration of hormone therapy, dose level of radiation therapy alone or associated with brachytherapy are controversial data in the literature. The therapeutic choice, multidisciplinary, depends on the age and comorbidity of the patient, the prognostic criteria of the pathology and the urinary function of the patient. Current research focuses on optimizing local and distant control of these aggressive forms and incorporates neoadjuvant or adjuvant chemotherapy and also new hormone therapies.},
keywords = {cancer, Cancer de la prostate de haut risque, Chemotherapy, Chimiothérapie, High-risk, Hormone therapy, Hormonothérapie, out_lab, Prostate, Radiothérapie, radiotherapy},
pubstate = {published},
tppubtype = {article}
}
@article{cancers12040944,
title = {Haute Couture or Ready-To-Wear? Tailored Pelvic Radiotherapy for Prostate Cancer Based on Individualized Sentinel Lymph Node Detection},
author = {Anne-Victoire Michaud and Benoit Samain and Ludovic Ferrer and Vincent Fleury and Melanie Dore and Mathilde Colombie and Claire Dupuy and Emmanuel Rio and Valentine Guimas and Thierry Rousseau and Maelle Le Thiec and Gregory Delpon and Caroline Rousseau and Stéphane Supiot},
url = {https://www.mdpi.com/2072-6694/12/4/944},
doi = {10.3390/cancers12040944},
issn = {2072-6694},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Cancers},
volume = {12},
number = {4},
abstract = {Prostate cancer (PCa) pelvic radiotherapy fields are defined by guidelines that do not consider individual variations in lymphatic drainage. We examined the feasibility of personalized sentinel lymph node (SLN)-based pelvic irradiation in PCa. Among a SLN study of 202 patients, we retrospectively selected 57 patients with a high risk of lymph node involvement. Each single SLN clinical target volume (CTV) was individually segmented and pelvic CTVs were contoured according to Radiation Therapy Oncology Group (RTOG) guidelines. We simulated a radiotherapy plan delivering 46 Gy and calculated the dose received by each SLN. Among a total of 332 abdominal SLNs, 305 pelvic SLNs (beyond the aortic bifurcation) were contoured (mean 5.4/patient). Based on standard guidelines, CTV missed 67 SLNs (22%), mostly at the common iliac level (40 SLNs). The mean distance between iliac vessels and the SLN was 11mm, and despite a 15mm margin around the iliac vessels, 9% of SLNs were not encompassed by the CTV. Moreover, 42 SLNs (63%) did not receive 95% of the prescribed dose. Despite a consensus on contouring guidelines, a significant proportion of SLNs were not included in the pelvic CTV and did not receive the prescribed dose. A tailored approach based on individual SLN detection would avoid underdosing pelvic lymph nodes that potentially contain tumor cells.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{MYLONA202040,
title = {Local dose analysis to predict acute and late urinary toxicities after prostate cancer radiotherapy: Assessment of cohort and method effects},
author = {Eugenia Mylona and Alessandro Cicchetti and Tiziana Rancati and Federica Palorini and Claudio Fiorino and Stéphane Supiot and Nicolas Magne and Gilles Crehange and Riccardo Valdagni and Oscar Acosta and Renaud Crevoisier},
url = {https://www.sciencedirect.com/science/article/pii/S0167814020301134},
doi = {https://doi.org/10.1016/j.radonc.2020.02.028},
issn = {0167-8140},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Radiotherapy and Oncology},
volume = {147},
pages = {40-49},
abstract = {Purpose 
To perform bladder dose-surface map (DSM) analysis for (1) identifying symptom-related sub-surfaces (Ssurf) and evaluating their prediction capability of urinary toxicity, (2) comparing DSM with dose-volume map (DVM) (method effect), and (3) assessing the reproducibility of DSM (cohort effect). 
Methods and materials 
Urinary toxicities were prospectively analyzed for 254 prostate cancer patients treated with IMRT/IGRT at 78/80 Gy. DSMs were generated by unfolding bladder surfaces in a 2D plane. Pixel-by-pixel analysis was performed to identify symptom-related Ssurf. Likewise, voxel-by-voxel DVM analysis was performed to identify sub-volumes (Svol). The prediction capability of Ssurf and Svol DVHs was assessed by logistic/Cox regression using the area under the ROC curve (AUC). The Ssurf localization and prediction capability were compared to (1) the Svol obtained by DVM analysis in the same cohort and (2) the Ssurf obtained from other DSM studies. 
Results Three Ssurf were identified in the bladder: posterior for acute retention (AUC = 0.64), posterior–superior for late retention (AUC = 0.68), and inferior–anterior–lateral for late dysuria (AUC = 0.73). Five Svol were identified: one in the urethra for acute incontinence and four in the posterior bladder part for acute and late retention, late dysuria, and hematuria. The overlap between Ssurf and Svol was moderate for acute retention, good for late retention, and bad for late dysuria, and AUCs ranged from 0.62 to 0.81. The prediction capabilities of Ssurf and Svol models were not significantly different. Among five symptoms comparable between cohorts, common Ssurf was found only for late dysuria, with a good spatial agreement. 
Conclusion 
Spatial agreement between methods is relatively good although DVM identified more sub-regions. Reproducibility of identified Ssurf between cohorts is low.},
keywords = {Dose–response relationship, out_lab, Predictive model, Prostate cancer, radiotherapy, Urinary toxicity},
pubstate = {published},
tppubtype = {article}
}
@article{LOUBERSAC2020S35,
title = {Prise en charge des rechutes oligométastatiques des cancers de prostate : actualités et perspectives},
author = {Thomas Loubersac and Valentine Guimas and Emmanuel Rio and Vincent Libois and Jérome Rigaud and Stéphane Supiot},
url = {https://www.sciencedirect.com/science/article/pii/S0007455120302769},
doi = {https://doi.org/10.1016/S0007-4551(20)30276-9},
issn = {0007-4551},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Bulletin du Cancer},
volume = {107},
number = {5, Supplement},
pages = {S35-S40},
abstract = {Résumé 
Le cancer de la prostate oligométastatique est une notion récente et polymorphe. Son émergence est concomitante du développement d’examens d’imagerie de plus en plus sensibles, notamment les tomographies par émission de positions (TEP) à la fluorocholine (18FCH) et au 68gallium-prostate-specific membrane antigen (Ga-PSMA). Chez des patients hormono-naïfs présentant un cancer de la prostate oligorécurrent (généralement moins de cinq métastases avec site primitif contrôlé), plusieurs études rétrospectives ont montré un bénéfice du traitement local des métastases soit par radiothérapie stéréotaxique, soit par curage ganglionnaire de rattrapage, au prix d’une faible toxicité. Des études de phase 2 randomisées ont montré que la radiothérapie stéréotaxique des méta stases permet de retarder l’introduction d’une hormonothérapie et d’améliorer la survie sans récidive biochimique, voire la survie globale. À la suite de ces résultats, les recommandations de l’european association of urology et de l’American Society for Radiation Oncology recommandent à présent le traitement direct de métastases par rapport à la surveillance. Nettement moins de données sont disponibles chez les patients en oligoprogression, définis comme des patients non ou peu symptomatiques porteurs d’un cancer de la prostate métastatique résistant à la castration présentant une augmentation de quelques métastases ganglionnaires ou osseuses. De nombreux essais en France et à l’international sont en cours pour confirmer la place du traitement direct des métastases. 
Summary 
Oligometastatic prostate cancer (PCa) is an intense area of research thanks to the development of novel PET tracers such as 18F-choline or 68Ga-PSMA. Several retrospective studies in patients with hormone-sensitive oligorecurrent PCa (usually up to 5 metastases with a controlled primary tumor) showed PSA response and a low toxicity profile of metastasis-directed therapies (MDT) such as Stereotactic Body Radiation Therapy (SBRT) or salvage lymph node dissection. More recently, randomized phase 2 studies showed that SBRT can delay the introduction of androgen deprivation, decrease biochemical relapses and increase overall survival. Regarding oligoprogressive metastatic castration-resistant PCa, limited data is however available. Based on these studies the European Association of Urology and the American Society of Radiotherapy EAU now recommend using MDT instead of observation. Several studies are undergoing in France and worldwide in order to confirm the exact role of MDT.},
note = {Questions d’actualités en Onco-Urologie},
keywords = {Cancer de prostate, Choline PET, Oligometastatic, oligométastatique, Oligoprogression, Oligoprogressive, Oligorécurrence, Oligorecurrent, out_lab, Prostate cancer, PSMA, Radiothérapie, SBRT, stéréotaxique, TEP-FCH},
pubstate = {published},
tppubtype = {article}
}
@article{plants9111508,
title = {Low Mannitol Concentrations in Arabidopsis thaliana Expressing Ectocarpus Genes Improve Salt Tolerance},
author = {Pramod Rathor and Tudor Borza and Yanhui Liu and Yuan Qin and Sophia Stone and Junzeng Zhang and Joseph P M Hui and Fabrice Berrue and Agnès Groisillier and Thierry Tonon and Svetlana Yurgel and Philippe Potin and Balakrishnan Prithiviraj},
url = {https://www.mdpi.com/2223-7747/9/11/1508},
doi = {10.3390/plants9111508},
issn = {2223-7747},
year  = {2020},
date = {2020-01-01},
journal = {Plants},
volume = {9},
number = {11},
abstract = {Mannitol is abundant in a wide range of organisms, playing important roles in biotic and abiotic stress responses. Nonetheless, mannitol is not produced by a vast majority of plants, including many important crop plants. Mannitol-producing transgenic plants displayed improved tolerance to salt stresses though mannitol production was rather low, in the &micro;M range, compared to mM range found in plants that innately produce mannitol. Little is known about the molecular mechanisms underlying salt tolerance triggered by low concentrations of mannitol. Reported here is the production of mannitol in Arabidopsis thaliana, by expressing two mannitol biosynthesis genes from the brown alga Ectocarpus sp. strain Ec32. To date, no brown algal genes have been successfully expressed in land plants. Expression of mannitol-1-phosphate dehydrogenase and mannitol-1-phosphatase genes was associated with the production of 42.3-52.7 nmol g&minus;1 fresh weight of mannitol, which was sufficient to impart salinity and temperature stress tolerance. Transcriptomics revealed significant differences in the expression of numerous genes, in standard and salinity stress conditions, including genes involved in K+ homeostasis, ROS signaling, plant development, photosynthesis, ABA signaling and secondary metabolism. These results suggest that the improved tolerance to salinity stress observed in transgenic plants producing mannitol in &micro;M range is achieved by the activation of a significant number of genes, many of which are involved in priming and modulating the expression of genes involved in a variety of functions including hormone signaling, osmotic and oxidative stress, and ion homeostasis.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{Storozhylova2020,
title = {An In Situ Hyaluronic Acid-Fibrin Hydrogel Containing Drug-Loaded Nanocapsules for Intra-Articular Treatment of Inflammatory Joint Diseases},
author = {Nataliya Storozhylova and José Crecente-Campo and David Cabaleiro and Luis Lugo and Christophe Dussouy and Sandra Sim{õ}es and Madalena Monteiro and Cyrille Grandjean and María J Alonso},
doi = {10.1007/s40883-020-00154-2},
issn = {23644141},
year  = {2020},
date = {2020-01-01},
journal = {Regenerative Engineering and Translational Medicine},
volume = {6},
number = {2},
pages = {201--216},
publisher = {Regenerative Engineering and Translational Medicine},
abstract = {Abstract: Intra-articular (IA) administration of drugs is an appealing route for the effective treatment of large-joint diseases. However, a key limitation of this route is the premature elimination of the injected drugs from the synovial cavity. The objective of this work was to develop an easily injectable controlled release system intended to prolong the activity of anti-inflammatory drugs in the articular cavity. The system was an in situ forming hydrogel, made of fibrin and hyaluronic acid (HA), loaded with nanocapsules (NCs). The NCs, consisting of an olive oil core surrounded by a HA shell, were loaded with two different drugs, dexamethasone (DMX) and a galectin-3 inhibitor. They presented a particle size in the range of 122–135 nm and a surface charge of − 29/− 31 mV. The gelation time, rheological properties and porosity of the system could be adjusted by different parameters, such as addition of fibrin crosslinkers factor XIII and α2-antiplasmin. The non-crosslinked HA-fibrin hydrogels containing 30% (v/v) NCs showed the capacity to control the release of the encapsulated drug, DMX, for 72 h in simulated synovial fluid. The preliminary in vivo evaluation of the system containing a galectin-3 inhibitor in an acute synovitis rat model showed a suppression of inflammation after IA administration compared with the non-treated control. In brief, this work shows the possibility to combine an in situ forming hydrogel and NCs as a drug delivery strategy for IA administration and suggests its potential for the treatment of arthropathies. Lay Summary: This work describes the development and characterization of a new in situ forming hydrogel adapted for intra-articular administration of anti-inflammatory drugs. The prolonged local delivery of these drugs is expected to improve the treatment of large-joint arthropathies. To achieve this objective, the hydrogel, made of biodegradable materials, was loaded with nanodeposits of drugs, named nanocapsules. The efficacy of the system, containing a new galectin-3 inhibitor as a drug candidate, was tested in a rat model of acute synovial inflammation. These results represent the first insights on the in vivo activity of a new galectin-3 inhibitor on a potential galectin-3 immunotherapeutic target for inflammatory joints diseases. [Figure not available: see fulltext.]},
keywords = {Arthropathies, Galectin-3 inhibitor, In situ hydrogel, Intra-articular drug delivery, Nanocapsules, team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Sato2020,
title = {Genome-enabled phylogenetic and functional reconstruction of an araphid pennate diatom Plagiostriata sp. CCMP470, previously assigned as a radial centric diatom, and its bacterial commensal},
author = {Shinya Sato and Deepak Nanjappa and Richard G Dorrell and Fabio Rocha Jimenez Vieira and Elena Kazamia and Leila Tirichine and Alaguraj Veluchamy and Roland Heilig and Jean Marc Aury and Olivier Jaillon and Patrick Wincker and Zoltan Fussy and Miroslav Obornik and Sergio A Mu{ñ}oz-Gómez and David G Mann and Chris Bowler and Adriana Zingone},
doi = {10.1038/s41598-020-65941-x},
issn = {20452322},
year  = {2020},
date = {2020-01-01},
journal = {Scientific Reports},
volume = {10},
number = {1},
pages = {1--12},
abstract = {Diatoms are an ecologically fundamental and highly diverse group of algae, dominating marine primary production in both open-water and coastal communities. The diatoms include both centric species, which may have radial or polar symmetry, and the pennates, which include raphid and araphid species and arose within the centric lineage. Here, we use combined microscopic and molecular information to reclassify a diatom strain CCMP470, previously annotated as a radial centric species related to Leptocylindrus danicus, as an araphid pennate species in the staurosiroid lineage, within the genus Plagiostriata. CCMP470 shares key ultrastructural features with Plagiostriata taxa, such as the presence of a sternum with parallel striae, and the presence of a highly reduced labiate process on its valve; and this evolutionary position is robustly supported by multigene phylogenetic analysis. We additionally present a draft genome of CCMP470, which is the first genome available for a staurosiroid lineage. 270 Pfams (19%) found in the CCMP470 genome are not known in other diatom genomes, which otherwise does not hold big novelties compared to genomes of non-staurosiroid diatoms. Notably, our DNA library contains the genome of a bacterium within the Rhodobacterales, an alpha-proteobacterial lineage known frequently to associate with algae. We demonstrate the presence of commensal alpha-proteobacterial sequences in other published algal genome and transcriptome datasets, which may indicate widespread and persistent co-occurrence.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{rastogi2020genomics,
title = {A genomics approach reveals the global genetic polymorphism, structure, and functional diversity of ten accessions of the marine model diatom Phaeodactylum tricornutum},
author = {Achal Rastogi and Fabio Rocha Jimenez Vieira and Anne-Flore Deton-Cabanillas and Alaguraj Veluchamy and Catherine Cantrel and Gaohong Wang and Pieter Vanormelingen and Chris Bowler and Gwenael Piganeau and Hanhua Hu and Others},
doi = {https://doi.org/10.1038/s41396-019-0528-3},
year  = {2020},
date = {2020-01-01},
journal = {The ISME journal},
volume = {14},
number = {2},
pages = {347--363},
publisher = {Nature Publishing Group},
abstract = {Diatoms emerged in the Mesozoic period and presently constitute one of the main primary producers in the world's ocean and are of a major economic importance. In the current study, using whole genome sequencing of ten accessions of the model diatom Phaeodactylum tricornutum, sampled at broad geospatial and temporal scales, we draw a comprehensive landscape of the genomic diversity within the species. We describe strong genetic subdivisions of the accessions into four genetic clades (A–D) with constituent populations of each clade possessing a conserved genetic and functional makeup, likely a consequence of the limited dispersal of P. tricornutum in the open ocean. We further suggest dominance of asexual reproduction across all the populations, as implied by high linkage disequilibrium. Finally, we show limited yet compelling signatures of genetic and functional convergence inducing changes in the selection pressure on many genes and metabolic pathways. We propose these findings to have significant implications for understanding the genetic structure of diatom populations in nature and provide a framework to assess the genomic underpinnings of their ecological success and impact on aquatic ecosystems where they play a major role. Our work provides valuable resources for functional genomics and for exploiting the biotechnological potential of this model diatom species.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{Fan2020,
title = {Single-base methylome profiling of the giant kelp Saccharina japonica reveals significant differences in DNA methylation to microalgae and plants},
author = {Xiao Fan and Wentao Han and Linhong Teng and Peng Jiang and Xiaowen Zhang and Dong Xu and Chang Li and Matteo Pellegrini and Chunhui Wu and Yitao Wang and Michelle Joyce Slade Kaczurowski and Xin Lin and Leila Tirichine and Thomas Mock and Naihao Ye},
doi = {10.1111/nph.16125},
issn = {14698137},
year  = {2020},
date = {2020-01-01},
journal = {New Phytologist},
volume = {225},
number = {1},
pages = {234--249},
abstract = {Brown algae have convergently evolved plant-like body plans and reproductive cycles, which in plants are controlled by differential DNA methylation. This contribution provides the first single-base methylome profiles of haploid gametophytes and diploid sporophytes of a multicellular alga. Although only c. 1.4% of cytosines in Saccharina japonica were methylated mainly at CHH sites and characterized by 5-methylcytosine (5mC), there were significant differences between life-cycle stages. DNA methyltransferase 2 (DNMT2), known to efficiently catalyze tRNA methylation, is assumed to methylate the genome of S. japonica in the structural context of tRNAs as the genome does not encode any other DNA methyltransferases. Circular and long noncoding RNA genes were the most strongly methylated regulatory elements in S. japonica. Differential expression of genes was negatively correlated with DNA methylation with the highest methylation levels measured in both haploid gametophytes. Hypomethylated and highly expressed genes in diploid sporophytes included genes involved in morphogenesis and halogen metabolism. The data herein provide evidence that cytosine methylation, although occurring at a low level, is significantly contributing to the formation of different life-cycle stages, tissue differentiation and metabolism in brown algae.},
keywords = {brown algae, BS-PCR, DNA methylation, DNMT2, gene expression, life-cycle stages, MeDIP-seq, team 5, WGBS-seq},
pubstate = {published},
tppubtype = {article}
}
@article{10.3389/fmars.2020.00189,
title = {Probing the Diversity of Polycomb and Trithorax Proteins in Cultured and Environmentally Sampled Microalgae},
author = {Xue Zhao and Anne Flore {Deton Cabanillas} and Alaguraj Veluchamy and Chris Bowler and Fabio Rocha Jimenez Vieira and Leila Tirichine},
url = {https://www.frontiersin.org/article/10.3389/fmars.2020.00189},
doi = {10.3389/fmars.2020.00189},
issn = {2296-7745},
year  = {2020},
date = {2020-01-01},
journal = {Frontiers in Marine Science},
volume = {7},
pages = {189},
abstract = {Polycomb (PcG) and Trithorax (TrxG) complexes are two evolutionarily conserved epigenetic regulatory components that act antagonistically to regulate the expression of genes involved in cell differentiation and development in multicellular organisms. The absence of PcG in both yeast models Saccharomyces cerevisiae and Schizosaccharomyces pombe suggested that polycomb proteins might have evolved together with the emergence of multicellular organisms. However, high throughput sequencing of several microalgal genomes and transcriptomes reveals an unprecedented abundance and diversity of genes encoding the components of these complexes. We report here the diversity of genes encoding PcG and TrxG proteins in microalgae from the Marine Microbial Eukaryote Transcriptome Sequencing Project database (MMETSP) and detected at broad scale in Tara Oceans genomics datasets using a highly sensitive method called eDAF (enhanced Domain Architecture Filtering). Further, we explored the correlation between environmental factors measured during the Tara Oceans expedition and transcript levels of PcG and TrxG components. PcG and TrxG are responsible for the deposition of a number of histone marks among which a TrxG associated mark, H3K4me3 which we profiled genome wide in the model diatom Phaeodactylum tricornutum to understand its role in microalgae and revisited the previously published histone code and co-occurrence with other histone marks including the antagonizing Polycomb deposited mark H3K27me3.},
keywords = {team 5, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Yaremenko2020a,
title = {Catalyst Development for the Synthesis of Ozonides and Tetraoxanes Under Heterogeneous Conditions: Disclosure of an Unprecedented Class of Fungicides for Agricultural Application},
author = {Ivan A Yaremenko and Peter S Radulov and Yulia Yu Belyakova and Arina A Demina and Dmitriy I Fomenkov and Denis V Barsukov and Irina R Subbotina and Fabrice Fleury and Alexander O Terent'ev},
doi = {10.1002/chem.201904555},
issn = {15213765},
year  = {2020},
date = {2020-01-01},
journal = {Chemistry - A European Journal},
volume = {26},
number = {21},
pages = {4734--4751},
abstract = {The catalyst H3+xPMo12−x+6Mox+5O40 supported on SiO2 was developed for peroxidation of 1,3- and 1,5-diketones with hydrogen peroxide with the formation of bridged 1,2,4,5-tetraoxanes and bridged 1,2,4-trioxolanes (ozonides) with high yield based on isolated products (up to 86 and 90 %, respectively) under heterogeneous conditions. Synthesis of peroxides under heterogeneous conditions is a rare process and represents a challenge for this field of chemistry, because peroxides tend to decompose on the surface of a catalyst. A new class of antifungal agents for crop protection, that is, cyclic peroxides: bridged 1,2,4,5-tetraoxanes and bridged ozonides, was discovered. Some ozonides and tetraoxanes exhibit a very high antifungal activity and are superior to commercial fungicides, such as Triadimefon and Kresoxim-methyl. It is important to note that none of the fungicides used in agricultural chemistry contains a peroxide fragment.},
keywords = {fungicides, heterogeneous catalysis, heteropolyacids, ozonides, Peroxides, team 3, tetraoxanes},
pubstate = {published},
tppubtype = {article}
}
@article{LAFONT2020129705,
title = {DNA-PKcs Ser2056 auto-phosphorylation is affected by an O-GlcNAcylation/phosphorylation interplay},
author = {Florian Lafont and Fabrice Fleury and Houda Benhelli-Mokrani},
url = {http://www.sciencedirect.com/science/article/pii/S0304416520302178},
doi = {https://doi.org/10.1016/j.bbagen.2020.129705},
issn = {0304-4165},
year  = {2020},
date = {2020-01-01},
journal = {Biochimica et Biophysica Acta (BBA) - General Subjects},
volume = {1864},
number = {12},
pages = {129705},
abstract = {Background DNA dependent Protein Kinase (DNA-PK) is an heterotrimeric complex regulating the Non Homologous End Joining (NHEJ) double strand break (DSB) repair pathway. The activity of its catalytic subunit (DNA-PKcs) is regulated by multiple phosphorylations, like the Ser2056 one that impacts DSB end processing and telomeres integrity. O-GlcNAcylation is a post translational modification (PTM) closely related to phosphorylation and its implication in the modulation of DNA-PKcs activity during the DNA Damage Response (DDR) is unknown. Methods Using IP techniques, and HeLa cell line, we evaluated the effect of pharmacological or siOGT mediated O-GlcNAc level modulation on DNA-PKcs O-GlcNAcylation. We used the RPA32 phosphorylation as a DNA-PKcs activity reporter substrate to evaluate the effect of O-GlcNAc modulators. Results We show here that human DNA-PKcs is an O-GlcNAc modified protein and that this new PTM is responsive to the cell O-GlcNAcylation level modulation. Our findings reveal that DNA-PKcs hypo O-GlcNAcylation affects its kinase activity and that the bleomycin-induced Ser2056 phosphorylation, is modulated by DNA-PKcs O-GlcNAcylation. Conclusions DNA-PKcs Ser2056 phosphorylation is antagonistically linked to DNA-PKcs O-GlcNAcylation level modulation. General significance Given the essential role of DNA-PKcs Ser2056 phosphorylation in the DDR, this study brings data about the role of cell O-GlcNAc level on genome integrity maintenance.},
keywords = {-GlcNAcylation, DNA repair, DNA-PKcs, HR, NHEJ, Phosphorylation, team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Vil2020,
title = {Ion exchange resin-catalyzed synthesis of bridged tetraoxanes possessing in vitro cytotoxicity against HeLa cancer cells},
author = {Vera A Vil' and Ivan A Yaremenko and Dmitri I Fomenkov and Dmitri O Levitsky and Fabrice Fleury and Alexander O Terent'ev},
url = {https://doi.org/10.1007/s10593-020-02722-4},
doi = {10.1007/s10593-020-02722-4},
issn = {1573-8353},
year  = {2020},
date = {2020-01-01},
journal = {Chemistry of Heterocyclic Compounds},
volume = {56},
number = {6},
pages = {722--726},
abstract = {Bridged 1,2,4,5-tetraoxanes were prepared using available acidic ion exchange resin with high yields despite the possibility of peroxide decomposition under heterogeneous conditions. The bridged tetraoxanes demonstrated high cytotoxicity against HeLa cancer cells in vitro, which in some cases was higher than that of cisplatin, artesunate, and dihydroartemisinin.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{RN31,
title = {Correction to: Cytokinin treated microcalli of Phelipanche ramosa: an efficient model for studying haustorium formation in holoparasitic plants},
author = {Estelle Billard and Vincent Goyet and Philippe Delavault and Philippe Simier and Grégory Montiel},
url = {https://doi.org/10.1007/s11240-020-01832-3 
https://link.springer.com/content/pdf/10.1007/s11240-020-01832-3.pdf},
doi = {10.1007/s11240-020-01832-3},
issn = {1573-5044},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Plant Cell, Tissue and Organ Culture (PCTOC)},
volume = {141},
number = {3},
pages = {555-555},
abstract = {The caption to Fig. 4 belonged to Fig. 5 and vice versa in the initial online publication. The original article has been corrected.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Teze2020,
title = {A Single Point Mutation Converts GH84 O-GlcNAc Hydrolases into Phosphorylases: Experimental and Theoretical Evidence},
author = {David Teze and Joan Coines and Lluís Raich and Valentina Kalichuk and Claude Solleux and Charles Tellier and Corinne André-Miral and Birte Svensson and Carme Rovira},
doi = {10.1021/jacs.9b09655},
issn = {15205126},
year  = {2020},
date = {2020-01-01},
journal = {Journal of the American Chemical Society},
volume = {142},
number = {5},
pages = {2120--2124},
abstract = {Glycoside hydrolases and phosphorylases are two major classes of enzymes responsible for the cleavage of glycosidic bonds. Here we show that two GH84 O-GlcNAcase enzymes can be converted to efficient phosphorylases by a single point mutation. Noteworthy, the mutated enzymes are over 10-fold more active than naturally occurring glucosaminide phosphorylases. We rationalize this novel transformation using molecular dynamics and QM/MM metadynamics methods, showing that the mutation changes the electrostatic potential at the active site and reduces the energy barrier for phosphorolysis by 10 kcaltextperiodcenteredmol-1. In addition, the simulations unambiguously reveal the nature of the intermediate as a glucose oxazolinium ion, clarifying the debate on the nature of such a reaction intermediate in glycoside hydrolases operating via substrate-assisted catalysis.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{RN2,
title = {Are root parasitic plants like any other plant pathogens?},
author = {Philippe Delavault},
url = {https://nph.onlinelibrary.wiley.com/doi/10.1111/nph.16504},
doi = {10.1111/nph.16504},
issn = {0028-646x},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {New Phytol},
volume = {226},
number = {3},
pages = {641-643},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{violo:hal-02990572,
title = {Homogenous Glycoconjugate Produced by Combined Unnatural Amino Acid Incorporation and Click-Chemistry for Vaccine Purposes},
author = {Typhaine Violo and Christophe Dussouy and Charles Tellier and Cyrille Grandjean and Emilie Camberlein},
url = {https://hal.archives-ouvertes.fr/hal-02990572},
doi = {10.3791/60821},
year  = {2020},
date = {2020-01-01},
journal = {Journal of visualized experiments : JoVE},
publisher = {JoVE},
keywords = {homogeneous glycoconjugate, s, synthetic biology, team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{RN3,
title = {Management of Infection by Parasitic Weeds: A Review},
author = {Monica Fernández-Aparicio and Philippe Delavault and Michael Timko},
url = {https://mdpi-res.com/d_attachment/plants/plants-09-01184/article_deploy/plants-09-01184.pdf},
doi = {10.3390/plants9091184},
issn = {2223-7747 (Print) 2223-7747},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Plants (Basel)},
volume = {9},
number = {9},
abstract = {Parasitic plants rely on neighboring host plants to complete their life cycle, forming vascular connections through which they withdraw needed nutritive resources. In natural ecosystems, parasitic plants form one component of the plant community and parasitism contributes to overall community balance. In contrast, when parasitic plants become established in low biodiversified agroecosystems, their persistence causes tremendous yield losses rendering agricultural lands uncultivable. The control of parasitic weeds is challenging because there are few sources of crop resistance and it is difficult to apply controlling methods selective enough to kill the weeds without damaging the crop to which they are physically and biochemically attached. The management of parasitic weeds is also hindered by their high fecundity, dispersal efficiency, persistent seedbank, and rapid responses to changes in agricultural practices, which allow them to adapt to new hosts and manifest increased aggressiveness against new resistant cultivars. New understanding of the physiological and molecular mechanisms behind the processes of germination and haustorium development, and behind the crop resistant response, in addition to the discovery of new targets for herbicides and bioherbicides will guide researchers on the design of modern agricultural strategies for more effective, durable, and health compatible parasitic weed control.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Visnapuu2020,
title = {Identification and characterization of a β-n-acetylhexosaminidase with a biosynthetic activity from the marine bacterium paraglaciecola hydrolytica S66T},
author = {Triinu Visnapuu and David Teze and Christian Kjeldsen and Aleksander Lie and Jens Øllgaard Duus and Corinne André-Miral and Lars Haastrup Pedersen and Peter Stougaard and Birte Svensson},
doi = {10.3390/ijms21020417},
issn = {14220067},
year  = {2020},
date = {2020-01-01},
journal = {International Journal of Molecular Sciences},
volume = {21},
number = {2},
publisher = {MDPI AG},
abstract = {β-N-Acetylhexosaminidases are glycoside hydrolases (GHs) acting on N-acetylated carbohydrates and glycoproteins with the release of N-acetylhexosamines. Members of the family GH20 have been reported to catalyze the transfer of N-acetylglucosamine (GlcNAc) to an acceptor, i.e., the reverse of hydrolysis, thus representing an alternative to chemical oligosaccharide synthesis. Two putative GH20 β-N-acetylhexosaminidases, PhNah20A and PhNah20B, encoded by the marine bacterium Paraglaciecola hydrolytica S66T, are distantly related to previously characterized enzymes. Remarkably, PhNah20A was located by phylogenetic analysis outside clusters of other studied β-N-acetylhexosaminidases, in a unique position between bacterial and eukaryotic enzymes. We successfully produced recombinant PhNah20A showing optimum activity at pH 6.0 and 50◦C, hydrolysis of GlcNAc β-1,4 and β-1,3 linkages in chitobiose (GlcNAc)2 and GlcNAc-1,3-β-Gal-1,4-β-Glc (LNT2), a human milk oligosaccharide core structure. The kinetic parameters of PhNah20A for p-nitrophenyl-GlcNAc and p-nitrophenyl-GalNAc were highly similar: kcat /KM being 341 and 344 mM−1 s−1, respectively. PhNah20A was unstable in dilute solution, but retained full activity in the presence of 0.5% bovine serum albumin (BSA). PhNah20A catalyzed the formation of LNT2, the non-reducing trisaccharide β-Gal-1,4-β-Glc-1,1-β-GlcNAc, and in low amounts the β-1,2-or β-1,3-linked trisaccharide β-Gal-1,4(β-GlcNAc)-1,x-Glc by a transglycosylation of lactose using 2-methyl-(1,2-dideoxy-α-d-glucopyrano)-oxazoline (NAG-oxazoline) as the donor. PhNah20A is the first characterized member of a distinct subgroup within GH20 β-N-acetylhexosaminidases.},
keywords = {Acceptor diversity, GH20, Glycoside hydrolase, Human milk oligosaccharides, Lacto-N-triose II, N-acetylhexosamine specificity, NAG-oxazoline, NMR, Phylogenetic analysis, team 2, Transglycosylation},
pubstate = {published},
tppubtype = {article}
}
@article{pmid32765559,
title = {Populations of the Parasitic Plant  Influence Their Seed Microbiota},
author = {Sarah Huet and Jean-Bernard Pouvreau and Erwan Delage and Sabine Delgrange and Coralie Marais and Muriel Bahut and Philippe Delavault and Philippe Simier and Lucie Poulin},
doi = {10.3389/fpls.2020.01075},
issn = {1664-462X},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Front Plant Sci},
volume = {11},
pages = {1075},
abstract = {Seeds of the parasitic weed  are well adapted to their hosts because they germinate and form haustorial structures to connect to roots in response to diverse host-derived molecular signals.  presents different genetic groups that are preferentially adapted to certain hosts. Since there are indications that microbes play a role in the interaction especially in the early stages of the interaction, we studied the microbial diversity harbored by the parasitic seeds with respect to their host and genetic group. Twenty-six seed lots from seven cropping plots of three different hosts-oilseed rape, tobacco, and hemp-in the west of France were characterized for their bacterial and fungal communities using 16S rRNA gene and ITS (Internal transcribed spacer) sequences, respectively. First seeds were characterized genetically using twenty microsatellite markers and phenotyped for their sensibility to various germination stimulants including strigolactones and isothiocyanates. This led to the distinction of three  groups that corresponded to their host of origin. The observed seed diversity was correlated to the host specialization and germination stimulant sensitivity within  species. Microbial communities were both clustered by host and plot of origin. The seed core microbiota was composed of seventeen species that were also retrieved from soil and was in lower abundances for bacteria and similar abundances for fungi compared to seeds. The host-related core microbiota of parasitic seeds was limited and presumably well adapted to the interaction with its hosts. Two microbial candidates of  species and  were especially identified in seeds from oilseed rape plots, suggesting their involvement in host recognition and specialization as well as seed fitness for  by improving the production of isothiocyanates from glucosinolates in the rhizosphere of oilseed rape.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Ostafe2020,
title = {One-shot optimization of multiple enzyme parameters: Tailoring glucose oxidase for pH and electron mediators},
author = {Raluca Ostafe and Nicolas Fontaine and David Frank and Matthieu {Ng Fuk Chong} and Radivoje Prodanovic and Rudy Pandjaitan and Bernard Offmann and Frédéric Cadet and Rainer Fischer},
doi = {10.1002/bit.27169},
issn = {10970290},
year  = {2020},
date = {2020-01-01},
journal = {Biotechnology and Bioengineering},
volume = {117},
number = {1},
pages = {17--29},
abstract = {Enzymes are biological catalysts with many industrial applications, but natural enzymes are usually unsuitable for industrial processes because they are not optimized for the process conditions. The properties of enzymes can be improved by directed evolution, which involves multiple rounds of mutagenesis and screening. By using mathematical models to predict the structure–activity relationship of an enzyme, and by defining the optimal combination of mutations in silico, we can significantly reduce the number of bench experiments needed, and hence the time and investment required to develop an optimized product. Here, we applied our innovative sequence–activity relationship methodology (innov'SAR) to improve glucose oxidase activity in the presence of different mediators across a range of pH values. Using this machine learning approach, a predictive model was developed and the optimal combination of mutations was determined, leading to a glucose oxidase mutant (P1) with greater specificity for the mediators ferrocene–methanol (12-fold) and nitrosoaniline (8-fold), compared to the wild-type enzyme, and better performance in three pH-adjusted buffers. The kcat/KM ratio of P1 increased by up to 121 folds compared to the wild type enzyme at pH 5.5 in the presence of ferrocene methanol.},
keywords = {artificial intelligence, directed evolution, multiple parameter improvement, protein sequence activity relationship, protein spectrum, rational screening, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33047515,
title = {Sarcoma treatment in the era of molecular medicine},
author = {Thomas Gp Grünewald and Marta Alonso and Sofia Avnet and Ana Banito and Stefan Burdach and Florencia Cidre-Aranaz and Gemma Di Pompo and Martin Distel and Heathcliff Dorado-Garcia and Javier Garcia-Castro and Laura González-González and Agamemnon E Grigoriadis and Merve Kasan and Christian Koelsche and Manuela Krumbholz and Fernando Lecanda and Silvia Lemma and Dario L Longo and Claudia Madrigal-Esquivel and Álvaro Morales-Molina and Julian Musa and Shunya Ohmura and Benjamin Ory and Miguel Pereira-Silva and Francesca Perut and Rene Rodriguez and Carolin Seeling and Nada Al Shaaili and Shabnam Shaabani and Kristina Shiavone and Snehadri Sinha and Eleni M Tomazou and Marcel Trautmann and Maria Vela and Yvonne Mh Versleijen-Jonkers and Julia Visgauss and Marta Zalacain and Sebastian J Schober and Andrej Lissat and William R English and Nicola Baldini and Dominique Heymann},
doi = {10.15252/emmm.201911131},
issn = {1757-4684},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {EMBO Mol Med},
volume = {12},
number = {11},
pages = {e11131},
abstract = {Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult-to-treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.},
keywords = {cancer, out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid32350079,
title = {Sphingolipid distribution at mitochondria-associated membranes (MAMs) upon induction of apoptosis},
author = {Vincent Mignard and Nolwenn Dubois and Didier Lanoé and Marie-Pierre Joalland and Lisa Oliver and Claire Pecqueur and Dominique Heymann and François Paris and François M Vallette and Lisenn Lalier},
doi = {10.1194/jlr.RA120000628},
issn = {1539-7262},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {J Lipid Res},
volume = {61},
number = {7},
pages = {1025--1037},
abstract = {The levels and composition of sphingolipids and related metabolites are altered in aging and in common disorders such as diabetes and cancers, as well as in neurodegenerative, cardiovascular, and respiratory diseases. Changes in sphingolipids have been implicated as being an essential step in mitochondria-driven cell death. However, little is known about the precise sphingolipid composition and modulation in mitochondria or related organelles. Here, we used LC-MS/MS to analyze the presence of key components of the ceramide metabolic pathway in vivo and in vitro in purified ER, mitochondria-associated membranes (MAMs), and mitochondria. Specifically, we analyzed the sphingolipids in the three pathways that generate ceramide: sphinganine in the de novo ceramide pathway, SM in the breakdown pathway, and sphingosine in the salvage pathway. We observed sphingolipid profiles in mouse liver, mouse brain, and a human glioma cell line (U251). We analyzed the quantitative and qualitative changes of these sphingolipids during staurosporine-induced apoptosis in U251 cells. Ceramide (especially C16-ceramide) levels increased during early apoptosis possibly through a conversion from mitochondrial sphinganine and SM, but sphingosine and lactosyl- and glycosyl-ceramide levels were unaffected. We also found that ceramide generation is enhanced in mitochondria when SM levels are decreased in the MAM. This decrease was associated with an increase in acid sphingomyelinase activity in MAM. We conclude that meaningful sphingolipid modifications occur in MAM, the mitochondria, and the ER during the early steps of apoptosis.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Hendrickx2020,
title = {Numerous severely twisted N-acetylglucosamine conformations found in the protein databank},
author = {Johann Hendrickx and Vinh Tran and Yves-Henri Sanejouand},
doi = {10.1002/prot.25957},
issn = {10970134},
year  = {2020},
date = {2020-01-01},
journal = {Proteins: Structure, Function and Bioinformatics},
volume = {88},
number = {10},
pages = {1376--1383},
abstract = {Taking advantage of the known planarity of the N-acetyl group of N-acetylglucosamine, an analysis of the quality of carbohydrate structures found in the protein databank was performed. Few obvious defects of the local geometry of the carbonyl group were observed. However, the N-acetyl group was often found in the less favorable cis conformation (12% of the cases). It was also found severely twisted in numerous instances, especially in structures with a resolution poorer than 1.9 Å determined between 2000 and 2015. Though the automated PDB-REDO procedure has proved able to improve nearly 85% of the structural models deposited to the PDB, and does prove able to cure most severely twisted conformations of the N-acetyl group, it fails to correct its high rate of cis conformations. More generally, for structures with a resolution poorer than 1.6 Å, it produces N-acetylglucosamine models in slightly poorer agreement with experimental data, as measured using real-space correlation coefficients. Significant improvements are thus still needed, at least as far as this carbohydrate structure is concerned.},
keywords = {carbohydrate, PDB-REDO, team 1, thesis, torsion angle},
pubstate = {published},
tppubtype = {article}
}
@article{liu2020comprehensive,
title = {Comprehensive History of CSP Genes: Evolution, Phylogenetic Distribution and Functions},
author = {Guoxia Liu and Ning Xuan and Balaji Rajashekar and Philippe Arnaud and Bernard Offmann and Jean-François Picimbon},
doi = {10.3390/genes11040413},
year  = {2020},
date = {2020-01-01},
journal = {Genes},
volume = {11},
number = {4},
pages = {413},
publisher = {Multidisciplinary Digital Publishing Institute},
abstract = {In this review we present the developmental, histological, evolutionary and functional properties of insect chemosensory proteins (CSPs) in insect species. CSPs are small globular proteins folded like a prism and notoriously known for their complex and arguably obscure function(s), particularly in pheromone olfaction. Here, we focus on direct functional consequences on protein function depending on duplication, expression and RNA editing. The result of our analysis is important for understanding the significance of RNA-editing on functionality of CSP genes, particularly in the brain tissue.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{pmid33184451,
title = {Characterization of Affitin proteolytic digestion in biorelevant media and improvement of their stabilities via protein engineering},
author = {Aurélie Loussouarn and Ghislaine Béhar and Frédéric Pecorari and Mikael Croyal and Axelle Renodon-Cornière},
doi = {10.1038/s41598-020-76855-z},
issn = {2045-2322},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Sci Rep},
volume = {10},
number = {1},
pages = {19703},
abstract = {Affitins are a novel class of small 7 kDa artificial proteins which can be used as antibody substitutes in therapeutic, diagnostic and biotechnological applications. One challenge for this type of protein agent is their behaviour in the context of oral administration. The digestive system is central, and biorelevant media have fast emerged as relevant and reliable tools for evaluating the bioavailability of drugs. This study describes, for the first time, the stability of Affitins under simulated gastric and intestinal digestion conditions. Affitins appear to be degraded into stable fragments in in vitro gastric medium. We identified cleavage sites generated by pepsin that were silenced by site-directed mutagenesis. This protein engineering allowed us to enhance Affitin properties. We showed that a mutant M1 containing a double mutation of amino acid residues 6 and 7 in H4 and C3 Affitins acquired a resistance against proteolytic digestion. In addition, these mutations were beneficial for target affinity, as well as for production yield. Finally, we found that the mutated residues kept or increased the important pH and temperature stabilities of Affitins. These improvements are particularly sought after in the development of engineered binding proteins for research tools, preclinical studies and clinical applications.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{DHINGRA202085,
title = {A glance into the evolution of template-free protein structure prediction methodologies},
author = {Surbhi Dhingra and Ramanathan Sowdhamini and Frédéric Cadet and Bernard Offmann},
url = {http://www.sciencedirect.com/science/article/pii/S0300908420300961},
doi = {https://doi.org/10.1016/j.biochi.2020.04.026},
issn = {0300-9084},
year  = {2020},
date = {2020-01-01},
journal = {Biochimie},
volume = {175},
pages = {85 - 92},
abstract = {Prediction of protein structures using computational approaches has been explored for over two decades, paving a way for more focused research and development of algorithms in comparative modelling, ab intio modelling and structure refinement protocols. A tremendous success has been witnessed in template-based modelling protocols, whereas strategies that involve template-free modelling still lag behind, specifically for larger proteins (&gt;150 a.a.). Various improvements have been observed in ab initio protein structure prediction methodologies overtime, with recent ones attributed to the usage of deep learning approaches to construct protein backbone structure from its amino acid sequence. This review highlights the major strategies undertaken for template-free modelling of protein structures while discussing few tools developed under each strategy. It will also briefly comment on the progress observed in the field of ab initio modelling of proteins over the course of time as seen through the evolution of CASP platform.},
keywords = {Ab initio modelling, artificial intelligence, Protein structure prediction, team 1, Template-Free modelling, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{catal10030291,
title = {A Machine Learning Approach for Efficient Selection of Enzyme Concentrations and Its Application for Flux Optimization},
author = {Anamya Ajjolli Nagaraja and Philippe Charton and Xavier F Cadet and Nicolas Fontaine and Mathieu Delsaut and Birgit Wiltschi and Alena Voit and Bernard Offmann and Cedric Damour and Brigitte Grondin-Perez and Frederic Cadet},
url = {https://www.mdpi.com/2073-4344/10/3/291},
doi = {10.3390/catal10030291},
issn = {2073-4344},
year  = {2020},
date = {2020-01-01},
journal = {Catalysts},
volume = {10},
number = {3},
abstract = {The metabolic engineering of pathways has been used extensively to produce molecules of interest on an industrial scale. Methods like gene regulation or substrate channeling helped to improve the desired product yield. Cell-free systems are used to overcome the weaknesses of engineered strains. One of the challenges in a cell-free system is selecting the optimized enzyme concentration for optimal yield. Here, a machine learning approach is used to select the enzyme concentration for the upper part of glycolysis. The artificial neural network approach (ANN) is known to be inefficient in extrapolating predictions outside the box: high predicted values will bump into a sort of “glass ceiling”. In order to explore this “glass ceiling” space, we developed a new methodology named glass ceiling ANN (GC-ANN). Principal component analysis (PCA) and data classification methods are used to derive a rule for a high flux, and ANN to predict the flux through the pathway using the input data of 121 balances of four enzymes in the upper part of glycolysis. The outcomes of this study are i. in silico selection of optimum enzyme concentrations for a maximum flux through the pathway and ii. experimental in vitro validation of the “out-of-the-box” fluxes predicted using this new approach. Surprisingly, flux improvements of up to 63% were obtained. Gratifyingly, these improvements are coupled with a cost decrease of up to 25% for the assay.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{pmid31906502,
title = {Influence of Radiotherapy Fractionation Schedule on the Tumor Vascular Microenvironment in Prostate and Lung Cancer Models},
author = {Karen Clément-Colmou and Vincent Potiron and Manon Pietri and Maëva Guillonneau and Emmanuel Jouglar and Sophie Chiavassa and Grégory Delpon and François Paris and Stéphane Supiot},
doi = {10.3390/cancers12010121},
issn = {2072-6694},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Cancers (Basel)},
volume = {12},
number = {1},
abstract = {Background. The tumor vasculature acts as an interface for the primary tumor. It regulates oxygenation, nutrient delivery, and treatment efficacy including radiotherapy. The response of the tumor vasculature to different radiation doses has been disparately reported. Whereas high single doses can induce endothelial cell death, improved vascular functionality has also been described in a various dose range, and few attempts have been made to reconcile these findings. Therefore, we aimed at comparing the effects of different radiation fractionation regimens on the tumor vascular microenvironment.

METHODS: Lewis lung and prostate PC3 carcinoma-derived tumors were irradiated with regimens of 10 × 2 Gy, 6 × 4 Gy, 3 × 8 Gy or 2 × 12 Gy fractions. The tumor vasculature phenotype and function was evaluated by immunohistochemistry for endothelial cells (CD31), pericytes (desmin, α-SMA), hypoxia (pimonidazole) and perfusion (Hoechst 33342).

RESULTS: Radiotherapy increased vascular coverage similarly in all fractionation regimens in both models. Vessel density appeared unaffected. In PC3 tumors, hypoxia was decreased and perfusion was enhanced in proportion with the dose per fraction. In LLC tumors, no functional changes were observed at  = 15 days, but increased perfusion was noticed earlier ( = 9-11 days).

CONCLUSION: The vascular microenvironment response of prostate and lung cancers to radiotherapy consists of both tumor/dose-independent vascular maturation and tumor-dependent functional parameters.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{10.3389/fnagi.2020.00103,
title = {Resveratrol Derivatives as Potential Treatments for Alzheimer’s and Parkinson’s Disease},
author = {Bruno Dutra Arbo and Corinne André-Miral and Raif Gregorio Nasre-Nasser and Lúcia Emanueli Schimith and Michele Goulart Santos and Dennis Costa-Silva and Ana Luiza Muccillo-Baisch and Mariana Appel Hort},
url = {https://www.frontiersin.org/article/10.3389/fnagi.2020.00103},
doi = {10.3389/fnagi.2020.00103},
issn = {1663-4365},
year  = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Frontiers in Aging Neuroscience},
volume = {12},
pages = {103},
abstract = {Neurodegenerative diseases are characterized by the progressive loss of neurons in different regions of the nervous system. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most prevalent neurodegenerative diseases, and the symptoms associated with these pathologies are closely related to the regions that are most affected by the process of neurodegeneration. Despite their high prevalence, currently, there is no cure or disease-modifying drugs for the treatment of these conditions. In the last decades, due to the need for the development of new treatments for neurodegenerative diseases, several authors have investigated the neuroprotective actions of naturally occurring molecules, such as resveratrol. Resveratrol is a stilbene found in several plants, including grapes, blueberries, raspberries, and peanuts. Studies have shown that resveratrol presents neuroprotective actions in experimental models of AD and PD, however, its clinical application is limited due to its rapid metabolism and low bioavailability. In this context, studies have proposed that structural changes in the resveratrol molecule, including glycosylation, alkylation, halogenation, hydroxylation, methylation, and prenylation could lead to the development of derivatives with enhanced bioavailability and pharmacological activity. Therefore, this review article aims to discuss how resveratrol derivatives could represent viable molecules in the search for new drugs for the treatment of AD and PD.},
keywords = {Funregiox, team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{10.1093/database/baaa095,
title = {STOREFISH 2.0: a database on the reproductive strategies of teleost fishes},
author = {Stéphane Téletchéa and Fabrice Téletchéa},
url = {https://doi.org/10.1093/database/baaa095},
doi = {10.1093/database/baaa095},
issn = {1758-0463},
year  = {2020},
date = {2020-01-01},
journal = {Database},
volume = {2020},
abstract = {Teleost fishes show the most outstanding reproductive diversity of all vertebrates. Yet to date, no one has been able to decisively explain this striking variability nor to perform large-scale phylogenetic analyses of reproductive modes. Here, we describe STrategies Of REproduction in FISH (STOREFISH) 2.0, an online database easing the sharing of an original data set on reproduction published in 2007, enriched with automated data extraction and presentation to display the knowledge acquired on temperate freshwater fish species. STOREFISH 2.0 contains the information for 80 freshwater fish species and 50 traits from the analysis of 1219 references. It is anticipated that this new database could be useful for freshwater biodiversity research, conservation, assessment and management.Database URL: www.storefish.org},
note = {baaa095},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1021/acs.joc.0c01927b,
title = {Access to Galectin-3 Inhibitors from Chemoenzymatic Synthons},
author = {Christophe Dussouy and Stéphane Téletchéa and Annie Lambert and Cathy Charlier and Iuliana Botez and Frédéric De Ceuninck and Cyrille Grandjean},
url = {https://doi.org/10.1021/acs.joc.0c01927},
doi = {10.1021/acs.joc.0c01927},
year  = {2020},
date = {2020-01-01},
journal = {The Journal of Organic Chemistry},
volume = {85},
number = {24},
pages = {16099-16114},
abstract = {Chemoenzymatic strategies are useful for providing both regio- and stereoselective access to bioactive oligosaccharides. We show herein that a glycosynthase mutant of a Thermus thermophilus α-glycosidase can react with unnatural glycosides such as 6-azido-6-deoxy-d-glucose/glucosamine to lead to β-d-galactopyranosyl-(1→3)-d-glucopyranoside or β-d-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-d-glucopyranoside derivatives bearing a unique azide function. Taking advantage of the orthogonality between the azide and the hydroxyl functional groups, the former was next selectively reacted to give rise to a library of galectin-3 inhibitors. Combining enzyme substrate promiscuity and bioorthogonality thus appears as a powerful strategy to rapidly access to sugar-based ligands},
note = {PMID: 33200927},
keywords = {impact, team 1, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{comby2020structure,
title = {Structure and Charge Heterogeneity in Isomeric Au25 (MBA) 18 Nanoclusters—Insights from Ion Mobility and Mass Spectrometry},
author = {Clothilde Comby-Zerbino and Franck Bertorelle and Philippe Dugourd and Rodolphe Antoine and Fabien Chirot},
doi = {10.1021/acs.jpca.0c03131},
year  = {2020},
date = {2020-01-01},
journal = {The Journal of Physical Chemistry A},
volume = {124},
number = {28},
pages = {5840--5848},
publisher = {ACS Publications},
abstract = {Atomically precise Au25(MBA)18 nanoclusters were investigated by mass spectrometry and ion mobility spectrometry. We show that clusters sharing the same chemical composition and bearing the same net charge may display different structures and different charge repartition patterns, namely, the number of charges corresponding to deprotonation of the ligand moieties through carboxyl groups is not the same for all detected species. Part of the observed heterogeneity is a consequence of spontaneous electron loss occurring in the gas phase, which modifies the net charge of the clusters while maintaining the initial (de)protonation state.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{russier2020second,
title = {Second harmonic scattering from mass characterized 2D graphene oxide sheets},
author = {Isabelle Russier-Antoine and Hussein Fakhouri and Srestha Basu and Franck Bertorelle and Philippe Dugourd and Pierre-François Brevet and Prajitha Velayudhan and Sabu Thomas and Nandakumar Kalarikkal and Rodolphe Antoine},
doi = {10.1039/D0CC00111B},
year  = {2020},
date = {2020-01-01},
journal = {Chemical Communications},
volume = {56},
number = {27},
pages = {3859--3862},
publisher = {Royal Society of Chemistry},
abstract = {In this communication, we report the second harmonic scattering from mass characterized 2D graphene oxide sheets dispersed in an aqueous suspension, in the femtosecond regime at 800 nm laser excitation. Charge-detection mass-spectrometry, performing at the single sheet level, allows for an exhaustive molar mass distribution and thus concentration for these 2D nanomaterials samples. The orientation-averaged hyperpolarizability value is (1.36 ± 0.15) × 10−25 esu as determined by the concentration-dependent harmonic scattering signal. In addition, the multi-photon excited fluorescence spectrum is characterized by a broad band in the visible range between 350 and 700 nm centered at about 500 nm.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{maysinger2020gold,
title = {Gold nanoclusters elicit homeostatic perturbations in glioblastoma cells and adaptive changes of lysosomes},
author = {Dusica Maysinger and Evan R Gran and Franck Bertorelle and Hussein Fakhouri and Rodolphe Antoine and Esha S Kaul and Dana M Samhadaneh and Ursula Stochaj},
doi = {10.7150/thno.37674},
year  = {2020},
date = {2020-01-01},
journal = {Theranostics},
volume = {10},
number = {4},
pages = {1633},
publisher = {Ivyspring International Publisher},
abstract = {Unique physicochemical features place gold nanoclusters at the forefront of nanotechnology for biological and biomedical applications. To date, information on the interactions of gold nanoclusters with biological macromolecules is limited and restricts their use in living cells. Methods: Our multidisciplinary study begins to fill the current knowledge gap by focusing on lysosomes and associated biological pathways in U251N human glioblastoma cells. We concentrated on lysosomes, because they are the intracellular destination for many nanoparticles, regulate cellular homeostasis and control cell survival. Results: Quantitative data presented here show that gold nanoclusters (with 15 and 25 gold atoms), surface-modified with glutathione or PEG, did not diminish cell viability at concentrations ≤1 µM. However, even at sublethal concentrations, gold nanoclusters modulated the abundance, positioning, pH and enzymatic activities of lysosomes. Gold nanoclusters also affected other aspects of cellular homeostasis. Specifically, they stimulated the transient nuclear accumulation of TFEB and Nrf2, transcription factors that promote lysosome biogenesis and stress responses. Moreover, gold nanoclusters also altered the formation of protein aggregates in the cytoplasm. The cellular responses elicited by gold nanoclusters were largely reversible within a 24-hour period. Conclusions: Taken together, this study explores the subcellular and molecular effects induced by gold nanoclusters and shows their effectiveness to regulate lysosome biology. Our results indicate that gold nanoclusters cause homeostatic perturbations without marked cell loss. Notably, cells adapt to the challenge inflicted by gold nanoclusters. These new insights provide a framework for the further development of gold nanocluster-based applications in biological sciences.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid31499274,
title = {Contalactone, a contaminant formed during chemical synthesis of the strigolactone reference GR24 is also a strigolactone mimic},
author = {Alexandre de Saint Germain and Pascal Retailleau and Stéphanie Norsikian and Vincent Servajean and Franck Pelissier and Vincent Steinmetz and Jean-Paul Pillot and Soizic Rochange and Jean-Bernard Pouvreau and François-Didier Boyer},
url = {hal-03010596v1 },
doi = {10.1016/j.phytochem.2019.112112},
issn = {1873-3700},
year  = {2019},
date = {2019-12-01},
urldate = {2019-12-01},
journal = {Phytochemistry},
volume = {168},
pages = {112112},
abstract = {Strigolactone (SL) plant hormones control plant architecture and are key players in both symbiotic and parasitic interactions. GR24, a synthetic SL analog, is the worldwide reference compound used in all bioassays for investigating the role of SLs in plant development and in rhizospheric interactions. In 2012, the first characterization of the SL receptor reported the detection of an unknown compound after incubation of GR24 samples with the SL receptor. We reveal here the origin of this compound (P270), which comes from a by-product formed during GR24 chemical synthesis. We present the identification of this by-product, named contalactone. A proposed chemical pathway for its formation is provided as well as an evaluation of its bioactivity on pea, Arabidopsis, root parasitic plant seeds and AM fungi, characterizing it as a SL mimic. Quality of GR24 samples can be easily checked by carrying out microscale hydrolysis in a basic aqueous medium to easily detect P270 as indicator of the presence of the contalactone impurity. In all cases, before being used for bioassays, GR24 must be careful purified by preparative HPLC.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Bogoeva2019,
title = {Binding of Gold(III) Porphyrin by the Pro-metastatic Regulatory Protein Human Galectin-3},
author = {Vanya Bogoeva and Miroslav Rangelov and Nadezhda Todorova and Annie Lambert and Clarisse Bridot and Anna Yordanova and Goedele Roos and Cyrille Grandjean and Julie Bouckaert},
doi = {10.3390/molecules24244561},
issn = {14203049},
year  = {2019},
date = {2019-12-01},
journal = {Molecules},
volume = {24},
number = {24},
publisher = {MDPI AG},
abstract = {Gold(III) porphyrin presents an attractive alternative to the use of, for example, cisplatin in chemotherapy. However, approaches that allow to selectively target cancer cells are highly sought. Many plant and mammalian lectins have been shown to bind oligosaccharide sequences of the aberrant glycosylation pattern found on cancerous tumors. For example human galectin-3, of the galectin family specific for ß-galactoside, is overexpressed in the extracellular matrix of tumorigenous and metastatic tissues. We searched for non-carbohydrate ligands for galectin-3 that can guide a cytotoxic drug to the cancer cells by maintaining its affinity for tumor associated carbohydrate antigens. Previous findings showed that zinc tetrasulfonatophenylporphyrin can bind galectin-3 with sub-micromolar affinity without disturbing lactose binding. Gold(III) porphyrin is not only cytotoxic to cancer cells, it knows also a potential application as photosensitiser in photodynamic therapy. We investigated the binding of gold(III) porphyrin to galectin-3 using different biophysical interaction techniques and demonstrated a low micromolar affinity of human galectin-3 for the cytotoxic compound. Co-crystallization attempts in order to understand the binding mode of gold porphyrin to galectin-3 failed, but molecular docking emphasized a highly populated secondary binding site that does not hinder lactose or Thomsen Friendenreich disaccharide binding. This suggests that gold(III) porphyrin might significantly enhance its concentration and delivery to cancer cells by binding to human galectin-3 that keeps its orientation towards tumor associated carbohydrate antigens.},
keywords = {Affinity, cytotoxicity, galectin-3, Gold porphyrin, Isothermal titration calorimetry, Microscale thermophoresis, Molecular docking, Molecular dynamics relaxation, team 2, Tryptophan fluorescence, Tumor associated carbohydrate antigen},
pubstate = {published},
tppubtype = {article}
}
@patent{michel2019novel,
title = {Novel Ulvan lyase and use thereof for cleaving polysaccharides},
author = {Gurvan Michel and Alexia Guillouzo and Bertille Massé and Sabine Génicot and Agnès Groisillier},
url = {https://patents.google.com/patent/US20190323048A1/en},
year  = {2019},
date = {2019-10-24},
number = {US20190323048A1},
publisher = {Google Patents},
location = {Centre National de la Recherche Scientifique CNRS, Sorbonne Universite},
abstract = {Some embodiments are directed to a novel ulvan lyase, a nucleic acid sequence coding for said enzyme, a vector comprising said coding sequence, a method for manufacturing said ulvan lyase, and a method for producing ulvan oligosaccharides with biological activity using said enzyme},
note = {US Patent App. 16/333,207},
keywords = {out_lab},
pubstate = {published},
tppubtype = {patent}
}
@inbook{pmid31625088,
title = {Affitins: Ribosome Display for Selection of Aho7c-Based Affinity Proteins},
author = {Valentina Kalichuk and Stanimir Kambarev and Ghislaine Béhar and Benjamin Chalopin and Axelle Renodon-Cornière and Barbara Mouratou and Frédéric Pecorari},
editor = {Zielonka S and Krah S},
doi = {10.1007/978-1-4939-9853-1_2},
isbn = {978-1-4939-9853-1},
year  = {2019},
date = {2019-10-18},
urldate = {2019-10-18},
journal = {Methods Mol Biol},
volume = {2070},
pages = {19--41},
edition = {Methods in Molecular Biology},
series = {Genotype Phenotype Coupling},
abstract = {Engineered protein scaffolds have made a tremendous contribution to the panel of affinity tools owing to their favorable biophysical properties that make them useful for many applications. In 2007, our group paved the way for using archaeal Sul7d proteins for the design of artificial affinity ligands, so-called Affitins. For many years, Sac7d and Sso7d have been used as molecular basis to obtain binders for various targets. Recently, we characterized their old gifted protein family and identified Aho7c, originating from Acidianus hospitalis, as the shortest member (60 amino-acids) with impressive stability (96.5 °C, pH 0-12). Here, we describe the construction of Aho7c combinatorial libraries and their use for selection of binders by ribosome display.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {inbook}
}
@article{pmid31594977,
title = {Hemophilia A and B mice, but not VWFmice, display bone defects in congenital development and remodeling after injury},
author = {Sarah Taves and Junjiang Sun and Eric W Livingston and Xin Chen and Jerome Amiaud and Regis Brion and William B Hannah and Ted A Bateman and Dominique Heymann and Paul E Monahan},
doi = {10.1038/s41598-019-50787-9},
issn = {2045-2322},
year  = {2019},
date = {2019-10-08},
urldate = {2019-10-08},
journal = {Sci Rep},
volume = {9},
number = {1},
pages = {14428},
abstract = {While joint damage is the primary co-morbidity of hemophilia, osteoporosis and osteopenia are also observed. Coagulation factor VIII deficient (FVIII) mice develop an osteoporotic phenotype in the absence of induced hemarthrosis that is exacerbated two weeks after an induced joint injury. Here we have compared comprehensively the bone health of clotting factor VIII, factor IX, and Von Willebrand Factor knockout (FVIII, FIX, and VWF respectively) mice both in the absence of joint hemorrhage and following induced joint injury. We found FVIII and FIX mice, but not VWF mice, developmentally have an osteoporotic phenotype. Unilateral induced hemarthrosis causes further bone damage in both FVIII and FIX mice, but has little effect on VWF bone health, indicating that the FVIII.VWF complex is not required for normal bone remodeling in vivo. To further investigate the bone healing following hemarthrosis in hemophilia we examined a two week time course using microCT, serum chemistry, and histological analysis. Elevated ratio of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL), increased osterix osteoblastic cells, and decreased smoothness of the cortical bone surface were evident within several days of injury, indicative of acute heterotopic mineralization along the cortical surface. This was closely followed by increased interleukin-6 (IL-6) levels, increased osteoclast numbers, and significant trabecular bone loss. Uncoupled and disorganized bone formation and resorption continued for the duration of the study resulting in significant deterioration of the joint. Further elucidation of the shared mechanisms underlying abnormal bone homeostasis in the absence of FVIII or FIX is needed to guide evidence-based approaches to the screening and treatment of the prevalent bone defects in hemophilia A and B.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Gheyouche2019,
title = {Docknmine, a web portal to assemble and analyse virtual and experimental interaction data},
author = {Ennys Gheyouche and Romain Launay and Jean Lethiec and Antoine Labeeuw and Caroline Roze and Alan Amossé and Stéphane Téletchéa},
doi = {10.3390/ijms20205062},
issn = {14220067},
year  = {2019},
date = {2019-10-01},
journal = {International Journal of Molecular Sciences},
volume = {20},
number = {20},
publisher = {MDPI AG},
abstract = {Scientists have to perform multiple experiments producing qualitative and quantitative data to determine if a compound is able to bind to a given target. Due to the large diversity of the potential ligand chemical space, the possibility of experimentally exploring a lot of compounds on a target rapidly becomes out of reach. Scientists therefore need to use virtual screening methods to determine the putative binding mode of ligands on a protein and then post-process the raw docking experiments with a dedicated scoring function in relation with experimental data. Two of the major difficulties for comparing docking predictions with experiments mostly come from the lack of transferability of experimental data and the lack of standardisation in molecule names. Although large portals like PubChem or ChEMBL are available for general purpose, there is no service allowing a formal expert annotation of both experimental data and docking studies. To address these issues, researchers build their own collection of data in flat files, often in spreadsheets, with limited possibilities of extensive annotations or standardisation of ligand descriptions allowing cross-database retrieval. We have conceived the dockNmine platform to provide a service allowing an expert and authenticated annotation of ligands and targets. First, this portal allows a scientist to incorporate controlled information in the database using reference identifiers for the protein (Uniprot ID) and the ligand (SMILES description), the data and the publication associated to it. Second, it allows the incorporation of docking experiments using forms that automatically parse useful parameters and results. Last, the web interface provides a lot of pre-computed outputs to assess the degree of correlations between docking experiments and experimental data.},
keywords = {Activity relationships, Drug discovery and design, Ligand analysis, Protein, Structure, team 1, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Tripathi2019,
title = {Investigation of phospholipase Cγ1 interaction with SLP76 using molecular modeling methods for identifying novel inhibitors},
author = {Neha Tripathi and Iyanar Vetrivel and Stéphane Téletchéa and Mickaël Jean and Patrick Legembre and Adèle D Laurent},
doi = {10.3390/ijms20194721},
issn = {14220067},
year  = {2019},
date = {2019-10-01},
journal = {International Journal of Molecular Sciences},
volume = {20},
number = {19},
publisher = {MDPI AG},
abstract = {The enzyme phospholipase C gamma 1 (PLCγ1) has been identified as a potential drug target of interest for various pathological conditions such as immune disorders, systemic lupus erythematosus, and cancers. Targeting its SH3 domain has been recognized as an efficient pharmacological approach for drug discovery against PLCγ1. Therefore, for the first time, a combination of various biophysical methods has been employed to shed light on the atomistic interactions between PLCγ1 and its known binding partners. Indeed, molecular modeling of PLCγ1 with SLP76 peptide and with previously reported inhibitors (ritonavir, anethole, daunorubicin, diflunisal, and rosiglitazone) facilitated the identification of the common critical residues (Gln805, Arg806, Asp808, Glu809, Asp825, Gly827, and Trp828) as well as the quantification of their interaction through binding energies calculations. These features are in agreement with previous experimental data. Such an in depth biophysical analysis of each complex provides an opportunity to identify new inhibitors through pharmacophore mapping, molecular docking and MD simulations. From such a systematic procedure, a total of seven compounds emerged as promising inhibitors, all characterized by a strong binding with PLCγ1 and a comparable or higher binding affinity to ritonavir (ΔGbind &lt; -25 kcal/mol), one of the most potent inhibitor reported till now.},
keywords = {Molecular docking, Molecular dynamics, Pharmacophore mapping, Phospholipase C gamma 1, SLP76, team 1, Virtual screening},
pubstate = {published},
tppubtype = {article}
}
@article{pmid31379856,
title = {Osteoimmunology of Oral and Maxillofacial Diseases: Translational Applications Based on Biological Mechanisms},
author = {Carla Alvarez and Gustavo Monasterio and Franco Cavalla and Luis A Córdova and Marcela Hernández and Dominique Heymann and Gustavo P Garlet and Timo Sorsa and Pirjo Pärnänen and Hsi-Ming Lee and Lorne M Golub and Rolando Vernal and Alpdogan Kantarci},
doi = {10.3389/fimmu.2019.01664},
issn = {1664-3224},
year  = {2019},
date = {2019-07-18},
urldate = {2019-07-18},
journal = {Front Immunol},
volume = {10},
pages = {1664},
abstract = {The maxillofacial skeleton is highly dynamic and requires a constant equilibrium between the bone resorption and bone formation. The field of osteoimmunology explores the interactions between bone metabolism and the immune response, providing a context to study the complex cellular and molecular networks involved in oro-maxillofacial osteolytic diseases. In this review, we present a framework for understanding the potential mechanisms underlying the immuno-pathobiology in etiologically-diverse diseases that affect the oral and maxillofacial region and share bone destruction as their common clinical outcome. These otherwise different pathologies share similar inflammatory pathways mediated by central cellular players, such as macrophages, T and B cells, that promote the differentiation and activation of osteoclasts, ineffective or insufficient bone apposition by osteoblasts, and the continuous production of osteoclastogenic signals by immune and local stromal cells. We also present the potential translational applications of this knowledge based on the biological mechanisms involved in the inflammation-induced bone destruction. Such applications can be the development of immune-based therapies that promote bone healing/regeneration, the identification of host-derived inflammatory/collagenolytic biomarkers as diagnostics tools, the assessment of links between oral and systemic diseases; and the characterization of genetic polymorphisms in immune or bone-related genes that will help diagnosis of susceptible individuals.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid31367241,
title = {Circulating Tumor Cells as a Tool for Assessing Tumor Heterogeneity},
author = {Marta Tellez-Gabriel and Marie-Françoise Heymann and Dominique Heymann},
doi = {10.7150/thno.34337},
issn = {1838-7640},
year  = {2019},
date = {2019-06-19},
urldate = {2019-06-19},
journal = {Theranostics},
volume = {9},
number = {16},
pages = {4580--4594},
abstract = {Tumor heterogeneity is the major cause of failure in cancer prognosis and prediction. Accurately detecting heterogeneity for the development of biomarkers and the detection of the clones resistant to therapy is one of the main goals of contemporary medicine. Metastases belong to the natural history of cancer. The present review gives an overview on the origin of tumor heterogeneity. Recent progress has made it possible to isolate and characterize circulating tumor cells (CTCs), which are the drivers of the disease between the primary sites and metastatic foci. The most recent methods for characterizing CTCs are summarized and we discuss the power of CTC profiling for analyzing tumor heterogeneity in early and advanced diseases.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid30982947,
title = {Whole-bacterium ribosome display selection for isolation of highly specific anti-Staphyloccocus aureus Affitins for detection- and capture-based biomedical applications},
author = {Ghislaine Béhar and Axelle Renodon-Cornière and Stanimir Kambarev and Petar Vukojicic and Nathalie Caroff and Stéphane Corvec and Barbara Mouratou and Frédéric Pecorari},
doi = {10.1002/bit.26989},
issn = {1097-0290},
year  = {2019},
date = {2019-05-15},
urldate = {2019-01-01},
journal = {Biotechnol Bioeng},
volume = {116},
number = {8},
pages = {1844--1855},
abstract = {Detection and capture methods using antibodies have been developed to ensure identification of pathogens in biological samples. Though antibodies have many attractive properties, they also have limitations and there are needs to expand the panel of available affinity proteins with different properties. Affitins, that we developed from the Sul7d proteins, are a solid class of affinity proteins, which can be used as substitutes to antibodies or to complement them. We report the generation and characterization of antibacterial Affitins with high specificity for Staphylococcus aureus. For the first time, ribosome display selections were carried out using whole-living-cell and naïve combinatorial libraries, which avoid production of protein targets and immunization of animals. We showed that Affitin C5 exclusively recognizes S. aureus among dozens of strains, including clinical ones. C5 binds staphylococcal Protein A (SpA) with a K  of 108 ± 2 nM and has a high thermostability (T   = 77.0°C). Anti-S. aureus C5 binds SpA or bacteria in various detection and capture applications, including ELISA, western blot analysis, bead-fishing, and fluorescence imaging. Thus, novel anti-bacteria Affitins which are cost-effective, stable, and small can be rapidly and fully designed in vitro with high affinity and specificity for a surface-exposed marker. This class of reagents can be useful in diagnostic and biomedical applications.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{AjjolliNagaraja2019,
title = {Flux prediction using artificial neural network (ANN) for the upper part of glycolysis},
author = {Anamya {Ajjolli Nagaraja} and Nicolas Fontaine and Mathieu Delsaut and Philippe Charton and Cedric Damour and Bernard Offmann and Brigitte Grondin-Perez and Frédéric Cadet},
editor = {Marie-Joelle Virolle},
url = {https://dx.plos.org/10.1371/journal.pone.0216178},
doi = {10.1371/journal.pone.0216178},
issn = {1932-6203},
year  = {2019},
date = {2019-05-01},
journal = {PLOS ONE},
volume = {14},
number = {5},
pages = {e0216178},
publisher = {Public Library of Science},
abstract = {The selection of optimal enzyme concentration in multienzyme cascade reactions for the highest product yield in practice is very expensive and time-consuming process. The modelling of biological pathways is a difficult process because of the complexity of the system. The mathematical modelling of the system using an analytical approach depends on the many parameters of enzymes which rely on tedious and expensive experiments. The artificial neural network (ANN) method has been successively applied in different fields of science to perform complex functions. In this study, ANN models were trained to predict the flux for the upper part of glycolysis as inferred by NADH consumption, using four enzyme concentrations i.e., phosphoglucoisomerase, phosphofructokinase, fructose-bisphosphate-aldolase, triose-phosphate-isomerase. Out of three ANN algorithms, the neuralnet package with two activation functions, “logistic” and “tanh” were implemented. The prediction of the flux was very efficient: RMSE and R2 were 0.847, 0.93 and 0.804, 0.94 respectively for logistic and tanh functions using a cross validation procedure. This study showed that a systemic approach such as ANN could be used for accurate prediction of the flux through the metabolic pathway. This could help to save a lot of time and costs, particularly from an industrial perspective. The R-code is available at: https://github.com/DSIMB/ANN-Glycolysis-Flux-Prediction.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{pmid30935573,
title = {Reoxygenation during radiotherapy in intermediate-risk prostate cancer},
author = {Stéphane Supiot and Caroline Rousseau and Mélanie Dore and Catherine Chèze-Le-Rest and Christine Kandel-Aznar and Vincent Potiron and Stéphane Guerif and François Paris and Ludovic Ferrer and Loïc Campion and Philippe Meingan and Grégory Delpon and Mathieu Hatt and Dimitris Visvikis},
doi = {10.1016/j.radonc.2018.12.022},
issn = {1879-0887},
year  = {2019},
date = {2019-04-01},
urldate = {2019-01-01},
journal = {Radiother Oncol},
volume = {133},
pages = {16--19},
abstract = {Hypoxia is a major risk factor of prostate cancer radioresistance. We evaluated hypoxia non-invasively, using F-Misonidazole PET/CT prior to radiotherapy and after a dose of 20 Gy in intermediate-risk prostate cancer patients. Decreased hypoxic volumes were observed in all patients, suggesting that radiotherapy induces early prostate tumor reoxygenation.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid30791889,
title = {Dose-painting multicenter phase III trial in newly diagnosed glioblastoma: the SPECTRO-GLIO trial comparing arm A standard radiochemotherapy to arm B radiochemotherapy with simultaneous integrated boost guided by MR spectroscopic imaging},
author = {Anne Laprie and Soléakhéna Ken and Thomas Filleron and Vincent Lubrano and Laure Vieillevigne and Fatima Tensaouti and Isabelle Catalaa and Sergio Boetto and Jonathan Khalifa and Justine Attal and Guillaume Peyraga and Carlos Gomez-Roca and Emmanuelle Uro-Coste and Georges Noel and Gilles Truc and Marie-Pierre Sunyach and Nicolas Magné and Marie Charissoux and Stéphane Supiot and Valérie Bernier and Muriel Mounier and Muriel Poublanc and Amandine Fabre and Jean-Pierre Delord and Elizabeth Cohen-Jonathan Moyal},
doi = {10.1186/s12885-019-5317-x},
issn = {1471-2407},
year  = {2019},
date = {2019-02-01},
urldate = {2019-02-01},
journal = {BMC Cancer},
volume = {19},
number = {1},
pages = {167},
abstract = {BACKGROUND: Glioblastoma, a high-grade glial infiltrating tumor, is the most frequent malignant brain tumor in adults and carries a dismal prognosis. External beam radiotherapy (EBRT) increases overall survival but this is still low due to local relapses, mostly occurring in the irradiation field. As the ratio of spectra of choline/N acetyl aspartate&gt; 2 (CNR2) on MR spectroscopic imaging has been described as predictive for the site of local relapse, we hypothesized that dose escalation on these regions would increase local control and hence global survival.

METHODS/DESIGN: In this multicenter prospective phase III trial for newly diagnosed glioblastoma, 220 patients having undergone biopsy or surgery are planned for randomization to two arms. Arm A is the Stupp protocol (EBRT 60 Gy on contrast enhancement + 2 cm margin with concomitant temozolomide (TMZ) and 6 months of TMZ maintenance); Arm B is the same treatment with an additional simultaneous integrated boost of intensity-modulated radiotherapy (IMRT) of 72Gy/2.4Gy delivered on the MR spectroscopic imaging metabolic volumes of CHO/NAA &gt; 2 and contrast-enhancing lesions or resection cavity. Stratification is performed on surgical and MGMT status.

DISCUSSION: This is a dose-painting trial, i.e. delivery of heterogeneous dose guided by metabolic imaging. The principal endpoint is overall survival. An online prospective quality control of volumes and dose is performed in the experimental arm. The study will yield a large amount of longitudinal multimodal MR imaging data including planning CT, radiotherapy dosimetry, MR spectroscopic, diffusion and perfusion imaging.

TRIAL REGISTRATION: NCT01507506 , registration date December 20, 2011.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Teletchea2019,
title = {Repository of enriched structures of proteins involved in the red blood cell environment (RESPIRE)},
author = {Stéphane Téletchéa and H Santuz and S Léonard and Catherine Etchebest},
doi = {10.1371/journal.pone.0211043},
issn = {19326203},
year  = {2019},
date = {2019-02-01},
journal = {PLoS ONE},
volume = {14},
number = {2},
publisher = {Public Library of Science},
abstract = {The Red Blood Cell (RBC) is a metabolically-driven cell vital for processes such a gas transport and homeostasis. RBC possesses at its surface exposing antigens proteins that are critical in blood transfusion. Due to their importance, numerous studies address the cell function as a whole but more and more details of RBC structure and protein content are now studied using massive state-of-the art characterisation techniques. Yet, the resulting information is frequently scattered in many scientific articles, in many databases and specialized web servers. To provide a more compendious view of erythrocytes and of their protein content, we developed a dedicated database called RESPIRE that aims at gathering a comprehensive and coherent ensemble of information and data about proteins in RBC. This cell-driven database lists proteins found in erythrocytes. For a given protein entry, initial data are processed from external portals and enriched by using state-of-the-art bioinformatics methods. As structural information is extremely useful to understand protein function and predict the impact of mutations, a strong effort has been put on the prediction of protein structures with a special treatment for membrane proteins. Browsing the database is available through text search for reference gene names or protein identifiers, through pre-defined queries or via hyperlinks. The RESPIRE database provides valuable information and unique annotations that should be useful to a wide audience of biologists, clinicians and structural biologists.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1021/acs.jpcc.9b08492,
title = {Influence of the Spatial Conformation of Charged Ligands on the Optical Properties of Gold Nanoclusters},
author = {Estelle Porret and Muriel Jourdan and Beatrice Gennaro and Clothilde Comby-Zerbino and Franck Bertorelle and Vanessa Trouillet and Xue Qiu and Claude Zoukimian and Didier Boturyn and Niko Hildebrandt and Rodolphe Antoine and Jean-Luc Coll and Xavier Le Guével},
url = {https://doi.org/10.1021/acs.jpcc.9b08492},
doi = {10.1021/acs.jpcc.9b08492},
year  = {2019},
date = {2019-01-01},
journal = {The Journal of Physical Chemistry C},
volume = {123},
number = {43},
pages = {26705-26717},
abstract = {Photoluminescent gold nanoclusters (Au NCs) were synthesized in one step in aqueous conditions using a mixture of glutathione and (mono or multivalent) glutathione-modified arginine peptides. By controlling the ratio of coligands, we investigated how the multivalency and the amount of arginines influenced the growth of Au NCs, their surface chemistry, their colloidal stability, and their optical properties. We demonstrated using two-dimensional nuclear magnetic resonance spectroscopy that the organization of the ligand on the Au surface was composed by an inner rigid layer and an outer flexible part via inter- and/or intraligand spatial proximity. This directly impacted the structure of the Au NCs, as confirmed by gel electrophoresis, high-resolution transmission electron microscopy, diffusion-ordered spectroscopy, and mass spectrometry. Increasing arginine content also induced an increase of positive surface charge and an enhancement of the near infrared emission intensity at ∼670 nm with quantum yield up to 10% validating the significant influence of the ligands to the optical properties of Au NCs.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{C9CP00829B,
title = {Sub-100 nanometer silver doped gold–cysteine supramolecular assemblies with enhanced nonlinear optical properties},
author = {Hussein Fakhouri and Martina Perić and Franck Bertorelle and Philippe Dugourd and Xavier Dagany and Isabelle Russier-Antoine and Pierre-François Brevet and Vlasta Bonačić-Koutecký and Rodolphe Antoine},
url = {http://dx.doi.org/10.1039/C9CP00829B},
doi = {10.1039/C9CP00829B},
year  = {2019},
date = {2019-01-01},
journal = {Phys. Chem. Chem. Phys.},
volume = {21},
pages = {12091-12099},
publisher = {The Royal Society of Chemistry},
abstract = {The ability of gold(i) thiolates to self-assemble into supramolecular architectures opens the route for a new class of nanomaterials with a unique structure–optical property relationship. However, for a confirmed structure–optical property relationship, a control of the supramolecular architectures is required. In this work, we report a simple synthesis of sub-100 nanometer gold–cysteine and silver doped gold–cysteine supramolecular assemblies. We explore in particular silver-doping as a strategy to enhance the optical properties of these supramolecular assemblies. By an accurate characterization of as-synthesized supramolecular nanoparticles, we have been able to measure for the first time, their absolute two-photon absorption cross-section, two-photon excited fluorescence cross-section and first hyperpolarizabilities at different near-IR wavelengths. Huge values are obtained for silver doped gold–cysteine supramolecular assemblies, as compared to their corresponding undoped counterpart. In addition, we employ DFT and TD-DFT methods to study the geometric and electronic structures of model gold–cysteine and silver doped gold–cysteine compounds in order to address the structure−linear/nonlinear optical property relationship. The aim is to gain insights into the origin of the nonlinear optical enhancement of silver-doped gold supramolecular assemblies.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{C9CP05262C,
title = {Ligand shell size effects on one- and two-photon excitation fluorescence of zwitterion functionalized gold nanoclusters},
author = {Martina Perić and Željka Sanader Maršić and Isabelle Russier-Antoine and Hussein Fakhouri and Franck Bertorelle and Pierre-François Brevet and Xavier le Guével and Rodolphe Antoine and Vlasta Bonačić-Koutecký},
url = {http://dx.doi.org/10.1039/C9CP05262C},
doi = {10.1039/C9CP05262C},
year  = {2019},
date = {2019-01-01},
journal = {Phys. Chem. Chem. Phys.},
volume = {21},
pages = {23916-23921},
publisher = {The Royal Society of Chemistry},
abstract = {Gold nanoclusters (Au NCs) are an emerging class of luminescent nanomaterials but still suffer from moderate photoluminescence quantum yields. Recent efforts have focused on tailoring their emission properties. Introducing zwitterionic ligands to cap the metallic kernel is an efficient approach to enhance their one-photon excitation fluorescence intensity. In this work, we extend this concept to the nonlinear optical regime, i.e., two-photon excitation fluorescence. For a proper comparison between theory and experiment, both ligand and solvent effects should be considered. The effects of ligand shell size and of aqueous solvent on the optical properties of zwitterion functionalized gold nanoclusters have been studied by performing quantum mechanics/molecular mechanics (QM/MM) simulations.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1080/17435390.2018.1543468,
title = {Organotypic and primary neural cultures as models to assess effects of different gold nanostructures on glia and neurons},
author = {Jeff Ji and Alexandre Moquin and Franck Bertorelle and Philip KY Chang and Rodolphe Antoine and Julia Luo and Anne R McKinney and Dusica Maysinger},
url = {https://doi.org/10.1080/17435390.2018.1543468},
doi = {10.1080/17435390.2018.1543468},
year  = {2019},
date = {2019-01-01},
journal = {Nanotoxicology},
volume = {13},
number = {3},
pages = {285-304},
publisher = {Taylor & Francis},
abstract = {Gold nanoparticles (AuNP) have unique physicochemical properties and have been used as delivery vehicles, contrast agents, and therapeutic compounds. Although the effects of AuNPs on peripheral tissues and immortalized cell lines have been extensively characterized, their effects on the central nervous system (CNS) are predominantly unknown. The main objective of the current study was to evaluate how AuNPs of varying sizes (1–100 nm), shapes (clusters, spheres, rods, flowers), and surfaces impact synaptic structures in the hippocampus, a brain structure often affected in neurodegeneration. Using a combination of organotypic hippocampal, as well as, primary neuronal, glial, and astrocytic cultures, we examined AuNPs impact on hippocampal dendritic spine density, internalization in various neural cells, and lysosomal status in astrocytes. Considering that neurons interact with astrocytes, and that lysosomes play a role in dendritic spine status, transcription factor TFEB and abundance of lysosomal marker, LAMP1 were evaluated. Both biomarkers were significantly increased in astrocytes exposed to AuNPs, suggesting that AuNPs not only enter lysosomes, but also increase lysosome biogenesis. Results from our studies show that AuNPs with poly(ethylene glycol) (AuNPs-PEG) or glutathione (AuNP-GSH) surfaces do not substantially decrease hippocampal dendritic spine density. Conversely, AuNPs coated with the detergent, CTAB, significantly decreased total spine density. Interestingly small gold nanoclusters (Au15(SG)13) with GSH reduced spine density, whereas larger gold nanoclusters (Au25(SG)18) with the same ligand did not. Thus, assessment of dendritic morphology, spine densities can reveal subtler changes of neural cells than cell death when exposed to nanoparticles, including AuNPs.},
note = {PMID: 30691378},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{nano9030457,
title = {Catenane Structures of Homoleptic Thioglycolic Acid-Protected Gold Nanoclusters Evidenced by Ion Mobility-Mass Spectrometry and DFT Calculations},
author = {Clothilde Comby-Zerbino and Martina Perić and Franck Bertorelle and Fabien Chirot and Philippe Dugourd and Vlasta Bonačić-Koutecký and Rodolphe Antoine},
url = {https://www.mdpi.com/2079-4991/9/3/457},
doi = {10.3390/nano9030457},
issn = {2079-4991},
year  = {2019},
date = {2019-01-01},
journal = {Nanomaterials},
volume = {9},
number = {3},
abstract = {Thiolate-protected metal nanoclusters have highly size- and structure-dependent physicochemical properties and are a promising class of nanomaterials. As a consequence, for the rationalization of their synthesis and for the design of new clusters with tailored properties, a precise characterization of their composition and structure at the atomic level is required. We report a combined ion mobility-mass spectrometry approach with density functional theory (DFT) calculations for determination of the structural and optical properties of ultra-small gold nanoclusters protected by thioglycolic acid (TGA) as ligand molecules, Au10(TGA)10. Collision cross-section (CCS) measurements are reported for two charge states. DFT optimized geometrical structures are used to compute CCSs. The comparison of the experimentally- and theoretically-determined CCSs allows concluding that such nanoclusters have catenane structures.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{https://doi.org/10.1002/rcm.8204,
title = {Direct determination of molecular weight distribution of calf-thymus DNAs and study of their fragmentation under ultrasonic and low-energy infrared irradiations. A charge detection mass spectrometry investigation},
author = {Mohammad A Halim and Franck Bertorelle and Tristan Doussineau and Rodolphe Antoine},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/rcm.8204},
doi = {https://doi.org/10.1002/rcm.8204},
year  = {2019},
date = {2019-01-01},
journal = {Rapid Communications in Mass Spectrometry},
volume = {33},
number = {S1},
pages = {35-39},
abstract = {Rationale Calf-thymus (CT-DNA) is widely used as a binding agent. The commercial samples are known to be “highly polymerized DNA” samples. CT-DNA is known to be fragile in particular upon ultrasonic wave irradiation. Degradation products could have dramatic consequences on its bio-sensing activity, and an accurate determination of the molecular weight distribution and stability of commercial samples is highly demanded. Methods We investigated the sensitivity of charge detection mass spectrometry (CDMS), a single-molecule MS method, both with single-pass and ion trap CDMS (“Benner” trap) modes to the determination of the composition and stability (under multiphoton IR irradiation) of calf-thymus DNAs. We also investigated the changes in molecular weight distributions in the course of sonication by irradiating ultrasonic waves to CT-DNA. Results We report, for the first time, the direct molecular weight (MW) distribution of DNA sodium salt from calf-thymus revealing two populations at high (~10 MDa) and low (~3 MDa) molecular weights. We evidence a transition between the high-MW to the low-MW distribution, confirming that the low-MW distribution results from degradation of CT-DNA. Finally, we report also IRMPD experiments carried out on trapped single-stranded linear DNAs from calf-thymus allowing extraction of their activation energy for unimolecular dissociation. Conclusions We show that single-pass CDMS is a direct, efficient and accurate MS-based approach to determine the composition of calf-thymus DNAs. Furthermore, ion trap CDMS allows us to evaluate the stability (both under multiphoton IR irradiation and in the course of sonication by irradiating ultrasonic wave) of calf-thymus DNAs.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid30616621,
title = {Meta-analysis of predictive models to assess the clinical validity and utility for patient-centered medical decision making: application to the CAncer of the Prostate Risk Assessment (CAPRA)},
author = {Marine Lorent and Haïfa Maalmi and Philippe Tessier and Stéphane Supiot and Etienne Dantan and Yohann Foucher},
doi = {10.1186/s12911-018-0727-2},
issn = {1472-6947},
year  = {2019},
date = {2019-01-01},
urldate = {2019-01-01},
journal = {BMC Med Inform Decis Mak},
volume = {19},
number = {1},
pages = {2},
abstract = {BACKGROUND: The Cancer of the Prostate Risk Assessment (CAPRA) score was designed and validated several times to predict the biochemical recurrence-free survival after a radical prostatectomy. Our objectives were, first, to study the clinical validity of the CAPRA score, and, second, to assess its clinical utility for stratified medicine from an original patient-centered approach.

METHODS: We proposed a meta-analysis based on a literature search using MEDLINE. Observed and predicted biochemical-recurrence-free survivals were compared to assess the calibration of the CAPRA score. Discriminative capacities were evaluated by estimating the summary time-dependent ROC curve. The clinical utility of the CAPRA score was evaluated according to the following stratified decisions: active monitoring for low-risk patients, prostatectomy for intermediate-risk patients, or radio-hormonal therapy for high risk patients. For this purpose, we assessed CAPRA's clinical utility in terms of its ability to maximize time-dependent utility functions (i.e. Quality-Adjusted Life-Years - QALYs).

RESULTS: We identified 683 manuscripts and finally retained 9 studies. We reported good discriminative capacities with an area under the SROCt curve at 0.73 [95%CI from 0.67 to 0.79], while graphical calibration seemed acceptable. Nevertheless, we also described that the CAPRA score was unable to discriminate between the three medical alternatives, i.e. it did not allow an increase in the number of life years in perfect health (QALYs) of patients with prostate cancer.

CONCLUSIONS: We confirmed the prognostic capacities of the CAPRA score. In contrast, we were not able to demonstrate its clinical usefulness for stratified medicine from a patient-centered perspective. Our results also highlighted the confusion between clinical validity and utility. This distinction should be better considered in order to develop predictive tools useful in practice.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{LATORZEFF2019S134,
title = {Late Toxicity and Quality of Life from GETUG-AFU 22 Study: A Multicenter Randomized Phase II Trial Comparing Radiotherapy +/- 6 Months of Degarelix as a Salvage Treatment for Patients with Detectable PSA after Radical Prostatectomy},
author = {I Latorzeff and S Guerif and J Fraisse and E Meyer and S Supiot and E Lagneau and E Deniaud-Alexandre and P Ronchin and A Benyoucef and L Cartier and H Hamidou and A Hasbini and G Crehange and P Pommier and N Magne and S Pelissier and E Gross and P Fourneret and L Salomon and P Sargos},
url = {https://www.sciencedirect.com/science/article/pii/S0360301619309587},
doi = {https://doi.org/10.1016/j.ijrobp.2019.06.123},
issn = {0360-3016},
year  = {2019},
date = {2019-01-01},
urldate = {2019-01-01},
journal = {International Journal of Radiation Oncology*Biology*Physics},
volume = {105},
number = {1, Supplement},
pages = {S134},
note = {Proceedings of the Amercian Society for Radiation Oncology 61st Annual Meeting},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{CARRIE2019S108,
title = {Medulloblastoma Molecular Subgroup and Hyperfractionated Radiation Therapy Alone for Standard Risk Medulloblastoma : Results of the Pool Data of MSFOP 1998 and 2007 Studies},
author = {C Carrie and V Kieffer and D Figarella-Branger and J Masliah-Planchon and S Bolle and J Leseur and S Supiot and A Laprie and V Bernier and C Dufour and A Huchet and B Coche-Dequeant and G Truc and C Vigneron and C Alapetite and JL Habrand and BM Dubray and C Colin and C Ferlay and L Padovani},
url = {https://www.sciencedirect.com/science/article/pii/S036030161931435X},
doi = {https://doi.org/10.1016/j.ijrobp.2019.06.600},
issn = {0360-3016},
year  = {2019},
date = {2019-01-01},
urldate = {2019-01-01},
journal = {International Journal of Radiation Oncology*Biology*Physics},
volume = {105},
number = {1, Supplement},
pages = {S108},
note = {Proceedings of the Amercian Society for Radiation Oncology 61st Annual Meeting},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid30682036,
title = {Intensity-modulated radiotherapy for prostate cancer with seminal vesicle involvement (T3b): A multicentric retrospective analysis},
author = {Flora Goupy and Stéphane Supiot and David Pasquier and Igor Latorzeff and Ulrike Schick and Erik Monpetit and Geoffrey Martinage and Chloé Hervé and Bernadette Le Proust and Joel Castelli and Renaud de Crevoisier},
doi = {10.1371/journal.pone.0210514},
issn = {1932-6203},
year  = {2019},
date = {2019-01-01},
urldate = {2019-01-01},
journal = {PLoS One},
volume = {14},
number = {1},
pages = {e0210514},
abstract = {OBJECTIVES: No study has reported clinical results of external-beam radiotherapy specifically for T3b prostate cancer. The possibility of escalating the dose to the involved seminal vesicles (ISV) while respecting the dose constraints in the organs at risk is thus so far not clearly demonstrated. The objective of the study was to analyze the dose distribution and the clinical outcome in a large series of patients who received IMRT for T3b prostate cancer.

MATERIALS AND METHODS: This retrospective analysis included all patients who received IMRT and androgen deprivation therapy for T3b prostate cancer, between 2008 and 2017, in six French institutions, with available MRI images and dosimetric data.

RESULTS: A total of 276 T3b patients were included. The median follow-up was 26 months. The median (range) prescribed doses (Gy) to the prostate and to the ISV were 77 (70-80) and 76 (46-80), respectively. The dose constraint recommendations were exceeded in less than 12% of patients for the rectum and the bladder. The 5-year risks of biochemical and clinical recurrences and cancer-specific death were 24.8%, 21.7%, and 10.3%, respectively. The 5-year risks of local, pelvic lymph node, and metastatic recurrences were 6.4%, 11.3%, and 15%, respectively. The number of involved lymph nodes (≤ 2 or ≥ 3) on MRI was the only significant prognostic factor in clinical recurrence (HR 9.86) and death (HR 2.78). Grade ≥ 2 acute and 5-year late toxicity rates were 13.2% and 12% for digestive toxicity, and 34% and 31.5% for urinary toxicity, respectively. The dose to the pelvic lymph node and the age were predictive of late digestive toxicity.

CONCLUSION: IMRT for T3b prostate cancer allows delivery of a curative dose in the ISV, with a moderate digestive toxicity but a higher urinary toxicity. Lymph node involvement increases the risk of recurrence and death.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid31293971,
title = {Feasibility of Dose Escalation in Patients With Intracranial Pediatric Ependymoma},
author = {Fatima Tensaouti and Anne Ducassou and Léonor Chaltiel and Stéphanie Bolle and Jean Louis Habrand and Claire Alapetite and Bernard Coche-Dequeant and Valérie Bernier and Line Claude and Christian Carrie and Laetitia Padovani and Xavier Muracciole and Stéphane Supiot and Aymeri Huchet and Julie Leseur and Christine Kerr and Grégorie Hangard and Albert Lisbona and Farid Goudjil and Régis Ferrand and Anne Laprie},
doi = {10.3389/fonc.2019.00531},
issn = {2234-943X},
year  = {2019},
date = {2019-01-01},
urldate = {2019-01-01},
journal = {Front Oncol},
volume = {9},
pages = {531},
abstract = { Pediatric ependymoma carries a dismal prognosis, mainly owing to local relapse within RT fields. The current prospective European approach is to increase the radiation dose with a sequential hypofractionated stereotactic boost. In this study, we assessed the possibility of using a simultaneous integrated boost (SIB), comparing VMAT vs. IMPT dose delivery.  The cohort included 101 patients. The dose to planning target volume (PTV59.4) was 59.4/1.8 Gy, and the dose to SIB volume (PTV67.6) was 67.6/2.05 Gy. Gross tumor volume (GTV) was defined as the tumor bed plus residual tumor, clinical target volume (CTV59.4) was GTV + 5 mm, and PTV59.4 was CTV59.4 + 3 mm. PTV67.6 was GTV+ 3 mm. After treatment plan optimization, quality indices and doses to target volume and organs at risk (OARs) were extracted and compared with the standard radiation doses that were actually delivered (median = 59.4 Gy [50.4 59.4]).  In most cases, the proton treatment resulted in higher quality indices ( &lt; 0.001). Compared with the doses that were initially delivered, mean, and maximum doses to some OARs were no higher with SIB VMAT, and significantly lower with protons ( &lt; 0.001). In the case of posterior fossa tumor, there was a lower dose to the brainstem with protons, in terms of V59 Gy, mean, and near-maximum (D2%) doses.  Dose escalation with intensity-modulated proton or photon SIB is feasible in some patients. This approach could be considered for children with unresectable residue or post-operative FLAIR abnormalities, particularly if they have supratentorial tumors. It should not be considered for infratentorial tumors encasing the brainstem or extending to the medulla.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Brissonnet2019a,
title = {Monitoring glycosidase activity for clustered sugar substrates, a study on β-glucuronidase},
author = {Yoan Brissonnet and Guillaume Compain and Brigitte Renoux and Eva Maria Krammer and Franck Daligault and David Deniaud and Sébastien Papot and Sébastien G Gouin},
doi = {10.1039/c9ra08847d},
issn = {20462069},
year  = {2019},
date = {2019-01-01},
journal = {RSC Advances},
volume = {9},
number = {69},
pages = {40263--40267},
abstract = {Determination of glycosidase hydrolysis kinetics for a monovalent sugar substrate is relatively straightforward and classically achieved by monitoring the fluorescence signal released from the sugar-conjugated probe after enzymatic hydrolysis. Naturally occuring sugar epitopes are, however, often clustered on biopolymers or at biological surfaces, and previous reports have shown that glycosidase hydrolytic rates can differ greatly with multivalent presentation of the sugar epitopes. New probes are needed to make it easier to interpret the importance of substrate clustering towards a specific enzyme activity. In this work, we developed multivalent glucuronide substrates attached to fluorescent amino-coumarines through self-immolative linkers to enable real time-monitoring of the hydrolysing activity of E.coli β-glucuronidases (GUS) towards clustered substrates. GUS are exoglycosidases of considerable therapeutic interest cleaving β-d-glucuronides and are found in the lysosomes, in the tumoral microenvironment, and are expressed by gut microbiota. GUS showed a much lower catalytic efficiency in hydrolysing clustered glucuronides due to a significantly lower enzymatic velocity and affinity for the substrates. GUS was 52-fold less efficient in hydrolysing GlcA substrates presented on an octameric silsequioxane (COSS) compared with a monovalent GlcA of similar chemical structure. Thus, kinetic and thermodynamic data of GUS hydrolysis towards multivalent glucuronides were easily obtained with these new types of enzymatically-triggered probes. More generally, adapting the substrate nature and valency of these new probes, should improve understanding of the impact of multivalency for a specific enzyme.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{ijms20225640,
title = {Novel Descriptors and Digital Signal Processing-Based Method for Protein Sequence Activity Relationship Study},
author = {Nicolas T Fontaine and Xavier F Cadet and Iyanar Vetrivel},
url = {https://www.mdpi.com/1422-0067/20/22/5640},
doi = {10.3390/ijms20225640},
issn = {1422-0067},
year  = {2019},
date = {2019-01-01},
journal = {International Journal of Molecular Sciences},
volume = {20},
number = {22},
abstract = {The work aiming to unravel the correlation between protein sequence and function in the absence of structural information can be highly rewarding. We present a new way of considering descriptors from the amino acids index database for modeling and predicting the fitness value of a polypeptide chain. This approach includes the following steps: (i) Calculating Q elementary numerical sequences (Ele_SEQ) depending on the encoding of the amino acid residues, (ii) determining an extended numerical sequence (Ext_SEQ) by concatenating the Q elementary numerical sequences, wherein at least one elementary numerical sequence is a protein spectrum obtained by applying fast Fourier transformation (FFT), and (iii) predicting a value of fitness for polypeptide variants (train and/or validation set). These new descriptors were tested on four sets of proteins of different lengths (GLP-2, TNF alpha, cytochrome P450, and epoxide hydrolase) and activities (cAMP activation, binding affinity, thermostability and enantioselectivity). We show that the use of multiple physicochemical descriptors coupled with the implementation of the FFT, taking into account the interactions between residues of amino acids within the protein sequence, could lead to very significant improvement in the quality of models and predictions. The choice of the descriptor or of the combination of descriptors and/or FFT is dependent on the couple protein/fitness. This approach can provide potential users with value added to existing mutant libraries where screening efforts have so far been unsuccessful in finding improved polypeptide mutants for useful applications.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Murik2019,
title = {Downregulation of mitochondrial alternative oxidase affects chloroplast function, redox status and stress response in a marine diatom},
author = {Omer Murik and Leila Tirichine and Judit Prihoda and Yann Thomas and Wagner L Ara{ú}jo and Andrew E Allen and Alisdair R Fernie and Chris Bowler},
doi = {10.1111/nph.15479},
issn = {14698137},
year  = {2019},
date = {2019-01-01},
journal = {New Phytologist},
volume = {221},
number = {3},
pages = {1303--1316},
abstract = {Diatom dominance in contemporary aquatic environments indicates that they have developed unique and effective mechanisms to cope with the rapid and considerable fluctuations that characterize these environments. In view of their evolutionary history from a secondary endosymbiosis, inter-organellar regulation of biochemical activities may be of particular relevance. Diatom mitochondrial alternative oxidase (AOX) is believed to play a significant role in supplying chloroplasts with ATP produced in the mitochondria. Using the model diatom Phaeodactylum tricornutum we generated AOX knockdown lines, and followed sensitivity to stressors, photosynthesis and transcriptome and metabolome profiles of wild-type and knockdown lines. We show here that expression of the AOX gene is upregulated by various stresses including H 2 O 2 , heat, high light illumination, and iron or nitrogen limitation. AOX knockdown results in hypersensitivity to stress. Knockdown lines also show significantly reduced photosynthetic rates and their chloroplasts are more oxidized. Comparisons of transcriptome and metabolome profiles suggest a strong impact of AOX activity on gene expression, which is carried through to the level of the metabolome. Our data provide evidence for the involvement of mitochondrial AOX in processes central to the cell biology of diatoms, revealing that cross-talk between mitochondria and chloroplasts is crucial for maintaining sensitivity to changing environments.},
keywords = {alternative oxidase (AOX), diatoms, metabolite profiling, mitochondria, oxidative stress, photosynthesis, team 5, transcriptome},
pubstate = {published},
tppubtype = {article}
}
@article{Caputi2019,
title = {Community-Level Responses to Iron Availability in Open Ocean Plankton Ecosystems},
author = {L Caputi and Q Carradec and D Eveillard and A Kirilovsky and E Pelletier and J J Pierella Karlusich and F Rocha Jimenez Vieira and E Villar and S Chaffron and S Malviya and E Scalco and S G Acinas and A Alberti and J -M Aury and A -S Benoiston and A Bertrand and T Biard and L Bittner and M Boccara and J R Brum and C Brunet and G Busseni and A Carratalà and H Claustre and L P Coelho and S Colin and S Daniello and C Da Silva and M Del Core and H Doré and S Gasparini and F Kokoszka and J -L Jamet and C Lejeusne and C Lepoivre and M Lescot and G Lima-Mendez and F Lombard and J Lukeš and N Maillet and M -A Madoui and E Martinez and M G Mazzocchi and M B Néou and J Paz-Yepes and J Poulain and S Ramondenc and J -B Romagnan and S Roux and D Salvagio Manta and R Sanges and S Speich and M Sprovieri and S Sunagawa and V Taillandier and A Tanaka and Leila Tirichine and Camille Trottier and J Uitz and A Veluchamy and J Veselá and F Vincent and S Yau and S Kandels-Lewis and S Searson and C Dimier and M Picheral and P Bork and E Boss and C de Vargas and M J Follows and N Grimsley and L Guidi and P Hingamp and E Karsenti and P Sordino and L Stemmann and M B Sullivan and A Tagliabue and A Zingone and L Garczarek and F DÓrtenzio and P Testor and F Not and M R DÁlcalà and P Wincker and C Bowler and D Iudicone},
doi = {10.1029/2018GB006022},
issn = {19449224},
year  = {2019},
date = {2019-01-01},
journal = {Global Biogeochemical Cycles},
volume = {33},
number = {3},
abstract = {Predicting responses of plankton to variations in essential nutrients is hampered by limited in situ measurements, a poor understanding of community composition, and the lack of reference gene catalogs for key taxa. Iron is a key driver of plankton dynamics and, therefore, of global biogeochemical cycles and climate. To assess the impact of iron availability on plankton communities, we explored the comprehensive bio-oceanographic and bio-omics data sets from Tara Oceans in the context of the iron products from two state-of-the-art global scale biogeochemical models. We obtained novel information about adaptation and acclimation toward iron in a range of phytoplankton, including picocyanobacteria and diatoms, and identified whole subcommunities covarying with iron. Many of the observed global patterns were recapitulated in the Marquesas archipelago, where frequent plankton blooms are believed to be caused by natural iron fertilization, although they are not captured in large-scale biogeochemical models. This work provides a proof of concept that integrative analyses, spanning from genes to ecosystems and viruses to zooplankton, can disentangle the complexity of plankton communities and can lead to more accurate formulations of resource bioavailability in biogeochemical models, thus improving our understanding of plankton resilience in a changing environment.},
keywords = {iron response, meta-omics, species networks, system biology, team 5},
pubstate = {published},
tppubtype = {article}
}
@misc{sanejouand:hal-02019920,
title = {No obvious change in the number density of galaxies up to z≈3.5},
author = {Yves-Henri Sanejouand},
url = {https://hal.archives-ouvertes.fr/hal-02019920},
year  = {2019},
date = {2019-01-01},
abstract = {The analysis of the cumulative count of sources of gamma-ray bursts as a function of their redshift strongly suggests that the number density of star-forming galaxies is roughly constant, up to z ≈ 3.5. The analysis of the cumulative count of galaxies in the Hubble Ultra Deep Field further shows that the overall number density of galaxies is constant as well, up to z ≈ 2 at least. Since ΛCDM does not seem able to cope with the age of old objects, both analyses were performed using a non-standard redshift-distance relationship.},
howpublished = {HAL},
note = {working paper or preprint},
keywords = {out_lab},
pubstate = {published},
tppubtype = {misc}
}
@unpublished{sanejouand:hal-02190771,
title = {A loss of photons along the line-of-sight can explain the Hubble diagram for quasars},
author = {Yves-Henri Sanejouand},
url = {https://hal.archives-ouvertes.fr/hal-02190771},
year  = {2019},
date = {2019-01-01},
abstract = {In order to explain the Hubble diagram for quasars, an alternative to ΛCDM is proposed, namely, a simple Newtonian cosmological model where the loss of photons along the line-of-sight mimics the cosmic distance-duality relation, up to z ≈ 0.2. According to this model, after ≈ 3 Gyr of travel, half of the photons emitted by a galaxy have been lost.
},
note = {working paper or preprint},
keywords = {out_lab},
pubstate = {published},
tppubtype = {unpublished}
}
@article{10.3389/fmicb.2018.03342,
title = {A Potential Role for Epigenetic Processes in the Acclimation Response to Elevated pCO2 in the Model Diatom Phaeodactylum tricornutum},
author = {Ruiping Huang and Jiancheng Ding and Kunshan Gao and Maria Helena de Carvalho and Leila Tirichine and Chris Bowler and Xin Lin},
url = {https://www.frontiersin.org/article/10.3389/fmicb.2018.03342},
doi = {10.3389/fmicb.2018.03342},
issn = {1664-302X},
year  = {2019},
date = {2019-01-01},
journal = {Frontiers in Microbiology},
volume = {9},
pages = {3342},
abstract = {Understanding of the molecular responses underpinning diatom responses to ocean acidification is fundamental for predicting how important primary producers will be shaped by the continuous rise in atmospheric CO2. In this study, we have analyzed global transcriptomic changes of the model diatom Phaeodactylum tricornutum following growth for 15 generations in elevated pCO2 by strand-specific RNA sequencing (ssRNA-seq). Our results indicate that no significant effects of elevated pCO2 and associated carbonate chemistry changes on the physiological performance of the cells were observed after 15 generations whereas the expression of genes encoding histones and other genes involved in chromatin structure were significantly down-regulated, while the expression of transposable elements (TEs) and genes encoding histone acetylation enzymes were significantly up-regulated. Furthermore, we identified a series of long non-protein coding RNAs (lncRNAs) specifically responsive to elevated pCO2, suggesting putative regulatory roles for these largely uncharacterized genome components. Taken together, our integrative analyses reveal that epigenetic elements such as TEs, histone modifications and lncRNAs may have important roles in the acclimation of diatoms to elevated pCO2 over short time scales and thus may influence longer term adaptive processes in response to progressive ocean acidification.},
keywords = {team 5},
pubstate = {published},
tppubtype = {article}
}
@article{Shao2019,
title = {Comparative characterization of putative chitin deacetylases from Phaeodactylum tricornutum and Thalassiosira pseudonana highlights the potential for distinct chitin-based metabolic processes in diatoms},
author = {Zhanru Shao and Yann Thomas and Lea Hembach and Xiaohui Xing and Delin Duan and Bruno M Moerschbacher and Vincent Bulone and Leila Tirichine and Chris Bowler},
doi = {10.1111/nph.15510},
issn = {14698137},
year  = {2019},
date = {2019-01-01},
journal = {New Phytologist},
volume = {221},
number = {4},
pages = {1890--1905},
abstract = {Chitin is generally considered to be present in centric diatoms but not in pennate species. Many aspects of chitin biosynthetic pathways have not been explored in diatoms. We retrieved chitin metabolic genes from pennate (Phaeodactylum tricornutum) and centric (Thalassiosira pseudonana) diatom genomes. Chitin deacetylase (CDA) genes from each genome (PtCDA and TpCDA) were overexpressed in P. tricornutum. We performed comparative analysis of their sequence structure, phylogeny, transcriptional profiles, localization and enzymatic activities. The chitin relevant proteins show complex subcellular compartmentation. PtCDA was likely acquired by horizontal gene transfer from prokaryotes, whereas TpCDA has closer relationships with sequences in Opisthokonta. Using transgenic P. tricornutum lines expressing CDA-green fluorescent protein (GFP) fusion proteins, PtCDA predominantly localizes to Golgi apparatus whereas TpCDA localizes to endoplasmic reticulum/chloroplast endoplasmic reticulum membrane. CDA-GFP overexpression upregulated the transcription of chitin synthases and potentially enhanced the ability of chitin synthesis. Although both CDAs are active on GlcNAc 5 , TpCDA is more active on the highly acetylated chitin polymer DA60. We have addressed the ambiguous characters of CDAs from P. tricornutum and T. pseudonana. Differences in localization, evolution, expression and activities provide explanations underlying the greater potential of centric diatoms for chitin biosynthesis. This study paves the way for in vitro applications of novel CDAs.},
keywords = {chitin, chitin deacetylase, chitosan, enzymatic activity, gene transformation, Phaeodactylum tricornutum, subcellular localization, team 5, Thalassiosira pseudonana},
pubstate = {published},
tppubtype = {article}
}
@article{duc_trapping_2019,
title = {Trapping a somatic endogenous retrovirus into a germline piRNA cluster immunizes the germline against further invasion},
author = {Céline Duc and Marianne Yoth and Silke Jensen and Nolwenn Mouniée and Casey M Bergman and Chantal Vaury and Emilie Brasset},
url = {https://genomebiology.biomedcentral.com/articles/10.1186/s13059-019-1736-x},
doi = {10.1186/s13059-019-1736-x},
issn = {1474-760X},
year  = {2019},
date = {2019-01-01},
urldate = {2019-01-01},
journal = {Genome Biology},
volume = {20},
number = {1},
pages = {127},
abstract = {Background: For species survival, the germline must faithfully transmit genetic information to the progeny. Transposable elements (TEs) constitute a significant threat to genome stability due to their mobility. In the metazoan germline, their mobilization is limited by a class of small RNAs called PIWI-interacting RNAs (piRNAs) produced by dedicated genomic loci called piRNA clusters. Although the piRNA pathway is an adaptive genomic immunity system, it remains unclear how the germline gains protection from a new transposon invasion. 
Results: To address this question, we analyze Drosophila melanogaster lines harboring a deletion within flamenco, a major piRNA cluster specifically expressed in somatic follicular cells. This deletion leads to derepression of the retrotransposon ZAM in the somatic follicular cells and subsequent germline genome invasion. In this mutant line, we identify de novo production of sense and antisense ZAM-derived piRNAs that display a germinal molecular signature. These piRNAs originated from a new ZAM insertion into a germline dual-strand piRNA cluster and silence ZAM expression specifically in germ cells. Finally, we find that ZAM trapping in a germinal piRNA cluster is a frequent event that occurs early during the isolation of the mutant line. 
Conclusions: Transposons can hijack the host developmental process to propagate whenever their silencing is lost. Here, we show that the germline can protect itself by trapping invading somatic-specific TEs into germline piRNA clusters. This is the first demonstration of “auto-immunization” of a germline endangered by mobilization of a surrounding somatic TE.},
keywords = {Drosophila, genome stability, germline, inheritance, piRNA cluster, piRNAs, team 5, Transposable elements},
pubstate = {published},
tppubtype = {article}
}
@article{VELIC2019187,
title = {Interactions of the Rad51 inhibitor DIDS with human and bovine serum albumins: Optical spectroscopy and isothermal calorimetry approaches},
author = {Denis Velic and Cathy Charlier and Milena Popova and Titouan Jaunet-Lahary and Zakaria Bouchouireb and Sébastien Henry and Pierre Weigel and Jean-Yves Masson and Adèle D Laurent and Igor Nabiev and Fabrice Fleury},
url = {http://www.sciencedirect.com/science/article/pii/S0300908419302743},
doi = {https://doi.org/10.1016/j.biochi.2019.09.016},
issn = {0300-9084},
year  = {2019},
date = {2019-01-01},
journal = {Biochimie},
volume = {167},
pages = {187--197},
abstract = {Rad51 is a key protein in DNA repair by homologous recombination and an important target for development of drugs in cancer therapy. 4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) has been used in clinic during the past 30 years as an inhibitor of anion transporters and channels. Recently DIDS has been demonstrated to affect Rad51-mediated homologous pairing and strand exchange, key processes in homologous recombination. Consequently, DIDS has been considered as a potential revertant of radio- and chemo-resistance of cancer cells, the major causes of therapy failure. Here, we have investigated the behavior of DIDS towards serum albumins. The effects of environmental factors, primarily, solvent polarity, on DIDS stability were evaluated, and the mechanisms of interaction of DIDS with human or bovine serum albumin were analyzed using isothermal calorimetry, circular dichroism and fluorescence spectroscopies. DIDS interaction with both serum albumins have been demonstrated, and the interaction characteristics have been determined. By comparing these characteristics for several DIDS derivatives, we have identified the DIDS moiety essential for the interaction. Furthermore, site competition data indicate that human albumin has two DIDS-binding sites: a high-affinity site in the IIIA subdomain and a low-affinity one in the IB subdomain. Molecular docking has revealed the key molecular moieties of DIDS responsible for its interactions in each site and shown that the IB site can bind two ligands. These findings show that binding of DIDS to serum albumin may change the balance between the free and bound DIDS forms, thereby affecting its bioavailability and efficacy against Rad51.},
keywords = {Blood albumin, DNA repair, impact, Protein-ligand interaction, Stilbene inhibitors, team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Chabot2019a,
title = {New phosphorylation sites of rad51 by c-met modulates presynaptic filament stability},
author = {Thomas Chabot and Alain Defontaine and Damien Marquis and Axelle Renodon-Corniere and Emmanuelle Courtois and Fabrice Fleury and Yvonnick Cheraud},
doi = {10.3390/cancers11030413},
issn = {20726694},
year  = {2019},
date = {2019-01-01},
journal = {Cancers},
volume = {11},
number = {3},
abstract = {Genomic instability through deregulation of DNA repair pathways can initiate cancer and subsequently result in resistance to chemo and radiotherapy. Understanding these biological mechanisms is therefore essential to overcome cancer. RAD51 is the central protein of the Homologous Recombination (HR) DNA repair pathway, which leads to faithful DNA repair of DSBs. The recombinase activity of RAD51 requires nucleofilament formation and is regulated by post-translational modifications such as phosphorylation. In the last decade, studies have suggested the existence of a relationship between receptor tyrosine kinases (RTK) and Homologous Recombination DNA repair. Among these RTK the c-MET receptor is often overexpressed or constitutively activated in many cancer types and its inhibition induces the decrease of HR. In this study, we show for the first time that c-MET is able to phosphorylate the RAD51 protein. We demonstrate in vitro that c-MET phosphorylates four tyrosine residues localized mainly in the subunit-subunit interface of RAD51. Whereas these post-translational modifications do not affect the presynaptic filament formation, they strengthen its stability against the inhibitor effect of the BRC peptide obtained from BRCA2. Taken together, these results confirm the role of these modifications in the regulation of the BRCA2-RAD51 interaction and underline the importance of c-MET in DNA damage response.},
keywords = {Cancer outcomes, DNA repair, HGFR kinase, Post-translational modification, RAD51 recombinase, team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Brinkø2019,
title = {Combining Click Reactions for the One-Pot Synthesis of Modular Biomolecule Mimetics},
author = {Anne Brinkø and Christian Risinger and Annie Lambert and Ola Blixt and Cyrille Grandjean and Henrik H Jensen},
doi = {10.1021/acs.orglett.9b02811},
issn = {15237052},
year  = {2019},
date = {2019-01-01},
journal = {Organic Letters},
volume = {21},
number = {18},
pages = {7544--7548},
abstract = {Here, we report on the first combined one-pot use of the two so-called "click reactions": The thiol-ene coupling and the copper-catalyzed alkyne-azide cycloaddition. These reactions were employed in an alternating and one-pot fashion to combine appropriately functionalized monomeric carbohydrate building blocks to create mimics of trisaccharides and tetrasaccharides as single anomers, with only minimal purification necessary. The deprotected oligosaccharide mimics were found to bind both plant lectins and human galectin-3.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{Pillot2019,
title = {Site-Specific Conjugation for Fully Controlled Glycoconjugate Vaccine Preparation},
author = {Aline Pillot and Alain Defontaine and Amina Fateh and Annie Lambert and Maruthi Prasanna and Mathieu Fanuel and Muriel Pipelier and Noemi Csaba and Typhaine Violo and Emilie Camberlein and Cyrille Grandjean},
doi = {10.3389/fchem.2019.00726},
issn = {22962646},
year  = {2019},
date = {2019-01-01},
journal = {Frontiers in Chemistry},
volume = {7},
number = {November},
pages = {1--9},
abstract = {Glycoconjugate vaccines are formed by covalently link a carbohydrate antigen to a carrier protein whose role is to achieve a long lasting immune response directed against the carbohydrate antigen. The nature of the sugar antigen, its length, its ratio per carrier protein and the conjugation chemistry impact on both structure and the immune response of a glycoconjugate vaccine. In addition it has long been assumed that the sites at which the carbohydrate antigen is attached can also have an impact. These important issue can now be addressed owing to the development of novel chemoselective ligation reactions as well as techniques such as site-selective mutagenesis, glycoengineering, or extension of the genetic code. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. A synthetic tetrasaccharide representative of the serotype 14 capsular polysaccharide of Streptococcus pneumoniae has been linked using the thiol/maleimide coupling chemistry to four different Pneumococcal surface adhesin A (PsaA) mutants, each harboring a single cysteine mutation at a defined position. Humoral response of these 1 to 1 carbohydrate antigen/PsaA conjugates have been assessed in mice. Our results showed that the carbohydrate antigen-PsaA connectivity impacts the anti-carrier response and raise questions about the design of glycoconjugate vaccine whereby the protein plays the dual role of immunogen and carrier.},
keywords = {chemoselective ligation, cysteine mutagenesis, glycoconjugate vaccine, pneumococcal vaccine, protein conjugation, team 2, thesis, thio/maleimide ligation},
pubstate = {published},
tppubtype = {article}
}
@article{PRASANNA201931,
title = {Semisynthetic glycoconjugate based on dual role protein/PsaA as a pneumococcal vaccine},
author = {Maruthi Prasanna and Daphnée Soulard and Emilie Camberlein and Nicolas Ruffier and Annie Lambert and François Trottein and Noemi Csaba and Cyrille Grandjean},
url = {http://www.sciencedirect.com/science/article/pii/S0928098718305487},
doi = {https://doi.org/10.1016/j.ejps.2018.12.013},
issn = {0928-0987},
year  = {2019},
date = {2019-01-01},
journal = {European Journal of Pharmaceutical Sciences},
volume = {129},
pages = {31--41},
abstract = {Pneumococcal infections remain a major public health concern worldwide. The currently available vaccines in the market are based on pneumococcal capsular polysaccharides but they still need to be improved to secure an optimal coverage notably in population at risk. To circumvent this, association of virulence pneumococcal proteins to the polysaccharide valencies has been proposed with the hope to observe an additive - if not synergistic - protective effect. Along this line, the use of the highly conserved and ubiquitous pneumococcal surface adhesin A (PsaA) as a protein carrier for a synthetic pneumococcal oligosaccharide is demonstrated herein for the first time. A tetrasaccharide mimicking functional antigenic determinants from the S. pneumoniae serotype 14 capsular polysaccharide (Pn14TS) was chemically synthesised. The mature PsaA (mPsaA) was expressed in E. coli and purified using affinity chromatography. The Pn14PS was conjugated to mPsaA using maleimide-thiol coupling chemistry to obtain mPsaA-Pn14PS conjugate (protein/sugar molar ratio: 1/5.4). The mPsaA retained the structural conformation after the conjugation and lyophilisation. The prepared glycoconjugate adjuvanted with α-galactosylceramide, a potent activator of invariant Natural Killer T cells, was tested in mice for its immunological response upon subcutaneous injection in comparison with mPsaA alone and a model BSA conjugate (BSA-Pn14PS, used here as a control). Mice immunised with the mPsaA-Pn14TS produced a robust IgG response against mPsaA and against the capsular polysaccharide from pneumococcal serotype 14. These data provide the basis for novel pneumococcal vaccine development.},
keywords = {Carbohydrate antigens, glycoconjugate vaccine, Pneumococcal surface adhesion A, Pneumococcus vaccine, team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Brissonnet2019b,
title = {Multivalent Thiosialosides and Their Synergistic Interaction with Pathogenic Sialidases},
author = {Yoan Brissonnet and Coralie Assailly and Amélie Saumonneau and Julie Bouckaert and Mike Maillasson and Clémence Petitot and Benoit Roubinet and Blanka Didak and Ludovic Landemarre and Clarisse Bridot and Ralf Blossey and David Deniaud and Xibo Yan and Julien Bernard and Charles Tellier and Cyrille Grandjean and Franck Daligault and Sébastien G Gouin},
doi = {10.1002/chem.201805790},
issn = {15213765},
year  = {2019},
date = {2019-01-01},
journal = {Chemistry - A European Journal},
volume = {25},
number = {9},
pages = {2358--2365},
abstract = {Sialidases (SAs) hydrolyze sialyl residues from glycoconjugates of the eukaryotic cell surface and are virulence factors expressed by pathogenic bacteria, viruses, and parasites. The catalytic domains of SAs are often flanked with carbohydrate-binding module(s) previously shown to bind sialosides and to enhance enzymatic catalytic efficiency. Herein, non-hydrolyzable multivalent thiosialosides were designed as probes and inhibitors of V. cholerae, T. cruzi, and S. pneumoniae (NanA) sialidases. NanA was truncated from the catalytic and lectinic domains (NanA-L and NanA-C) to probe their respective roles upon interacting with sialylated surfaces and the synthetically designed di- and polymeric thiosialosides. The NanA-L domain was shown to fully drive NanA binding, improving affinity for the thiosialylated surface and compounds by more than two orders of magnitude. Importantly, each thiosialoside grafted onto the polymer was also shown to reduce NanA and NanA-C catalytic activity with efficiency that was 3000-fold higher than that of the monovalent thiosialoside reference. These results extend the concept of multivalency for designing potent bacterial and parasitic sialidase inhibitors.},
keywords = {d-zyme, enzymes, glycoclusters, Glycosidases, Inhibition, sialidases, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{Naretto2019,
title = {The agar-specific hydrolase ZgAgaC from the marine bacterium Zobellia galactanivorans defines a new GH16 protein subfamily},
author = {Anaïs Naretto and Mathieu Fanuel and David Ropartz and Hélène Rogniaux and Robert Larocque and Mirjam Czjzek and Charles Tellier and Gurvan Michel},
doi = {10.1074/jbc.RA118.006609},
issn = {1083351X},
year  = {2019},
date = {2019-01-01},
journal = {Journal of Biological Chemistry},
volume = {294},
number = {17},
pages = {6923--6939},
abstract = {Agars are sulfated galactans from red macroalgae and are composed of a D-galactose (G unit) and L-galactose (L unit) alternatively linked by α-1, 3 and β-1, 4 glycosidicbonds. The sepolysaccharides display high complexity, with numerous modifications of their backbone (e.g. presence of a 3, 6-anhydro-bridge (LA unit) and sulfations and methylation). Currently, bacterial polysaccharidases that hydrolyze agars (α-agarases and α-porphyranases) have been characterized on simple agarose and more rarely on porphyran, a polymer containing both agarobiose (G-LA) and porphyranobiose (GL6S) motifs. How bacteria can degrade complex agars remains therefore an open question. Here, we studied an enzyme from the marine bacterium Zobellia galactanivorans (ZgAgaC) that is distantly related to the glycoside hydrolase 16 (GH16) family α-agarases and α-porphyranases. Using a large red algae collection, we demonstrate that ZgAgaC hydrolyzes not only agarose but also complex agars from Ceramiales species. Using tandem MS analysis, we elucidated the structure of a purified hexasaccharide product, L6S-G-LA2Me-G(2Pentose)-LA2S-G, released by the activity of ZgAgaC on agar extracted from Osmundea pinnatifida. By resolving the crystal structure of ZgAgaC at high resolution (1.3 Å) and comparison with the structures of ZgAgaB and ZgPorA in complex with their respective substrates, we determined that ZgAgaC recognizes agarose via a mechanism different from that of classical α-agarases. Moreover, we identified conserved residues involved in the binding of complex oligoagars and demonstrate a probable influence of the acidic polysaccharide's pH microenvironment on hydrolase activity. Finally, a phylogenetic analysis supported the notion that ZgAgaC homologs define a new GH16 subfamily distinct from α-porphyranases and classical α-agarases.},
keywords = {agar, crystal structure, evolution, gh16, Glycoside hydrolase, marine bacteria, mass spectrometry, microenvironment, ph, red algae, sulfated polysaccharide, team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{RN7,
title = {CYP707As are effectors of karrikin and strigolactone signalling pathways in Arabidopsis thaliana and parasitic plants},
author = {Guillaume Brun and Séverine Thoiron and Lukas Braem and Jean-Bernard Pouvreau and Grégory Montiel and Marc-Marie Lechat and Philippe Simier and Kris Gevaert and Sophie Goormachtig and Philippe Delavault},
url = {https://onlinelibrary.wiley.com/doi/10.1111/pce.13594},
doi = {10.1111/pce.13594},
issn = {0140-7791},
year  = {2019},
date = {2019-01-01},
urldate = {2019-01-01},
journal = {Plant Cell Environ},
volume = {42},
number = {9},
pages = {2612-2626},
abstract = {Karrikins stimulate Arabidopsis thaliana germination, whereas parasitic weeds of the Orobanchaceae family have evolved to respond to host-exuded compounds such as strigolactones, dehydrocostus lactone, and 2-phenylethyl isothiocyanate. In Phelipanche ramosa, strigolactone-induced germination was shown to require one of the CYP707A proteins involved in abscisic acid catabolism. Here, germination and gene expression were analysed to investigate the role of CYP707As in germination of both parasitic plants and Arabidopsis upon perception of germination stimulants, after using pharmacological inhibitors and Arabidopsis mutants disrupting germination signals. CYP707A genes were up-regulated upon treatment with effective germination stimulants in both parasitic plants and Arabidopsis. Obligate parasitic plants exhibited both intensified up-regulation of CYP707A genes and increased sensitivity to the CYP707A inhibitor abscinazole-E2B, whereas Arabidopsis cyp707a mutants still positively responded to germination stimulation. In Arabidopsis, CYP707A regulation required the canonical karrikin signalling pathway KAI2/MAX2/SMAX1 and the transcription factor WRKY33. Finally, CYP707As and WRKY33 also modulated Arabidopsis root architecture in response to the synthetic strigolactone rac-GR24, and wrky33-1 exhibited a shoot hyperbranched phenotype. This study suggests that the lack of host-independent germination in obligate parasites is associated with an exacerbated CYP707A induction and that CYP707As and WRKY33 are new players involved in a variety of strigolactone/karrikin responses.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{RN32,
title = {Genetic differentiation and host preference reveal non-exclusive host races in the generalist parasitic weed Phelipanche ramosa},
author = {Bojana Stojanova and Régine Delourme and Philippe Duffé and Philippe Delavault and Philippe Simier},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/wre.12353 
https://onlinelibrary.wiley.com/doi/10.1111/wre.12353},
doi = {https://doi.org/10.1111/wre.12353},
issn = {0043-1737},
year  = {2019},
date = {2019-01-01},
urldate = {2019-01-01},
journal = {Weed Research},
volume = {59},
number = {2},
pages = {107-118},
abstract = {Summary We developed 20 microsatellite markers to genotype over 100 populations of the parasitic weed Phelipanche ramosa, which covers a wide host crop and geographic range. A representative core collection of 15 populations was also used in cross-infestation assays to study host preference during germination, attachment and shoot formation. We observed low genetic differentiation within most of the populations, but high genetic differentiation between populations partitioned into 3 genetic groups with different host preferences and geographic distributions. Genetic group 1 is detected exclusively in western France and on various host crops, notably winter oilseed rape (WOSR) and not hemp. Cross-infection assays confirmed its incompatibility with hemp and showed its preference for WOSR and tobacco in terms of germination and attachment success. The group 2 populations share a large geographic distribution in France and Europe, low germination success with WOSR and high germination success, attachment success and shoot formation with hemp, tobacco or tomato. The subclades 2a and 2b include most of the French populations in hemp crops in eastern France and in tobacco fields in several European countries respectively. The genetic analyses revealed the potential of the three groups to increase their geographic range in the future. Intermediate genetic groups showed higher intrapopulation diversity and represent potential stocks for new host race emergence. Those findings argue in favour of the existence of host races in P. ramosa and should be considered for appropriate management strategies, notably in breeding programmes for resistance against this parasitic weed.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{LeCaignec2019,
title = {RPL13 Variants Cause Spondyloepimetaphyseal Dysplasia with Severe Short Stature},
author = {Cédric Le Caignec and Benjamin Ory and François Lamoureux and Marie Francoise O'Donohue and Emilien Orgebin and Pierre Lindenbaum and Stéphane Téletchéa and Manon Saby and Anna Hurst and Katherine Nelson and Shawn R Gilbert and Yael Wilnai and Leonid Zeitlin and Eitan Segev and Robel Tesfaye and Mathilde Nizon and Benjamin Cogne and Stéphane Bezieau and Loic Geoffroy and Antoine Hamel and Emmanuelle Mayrargue and Beno{î}t de Courtivron and Aliette Decock-Giraudaud and Céline Charrier and Olivier Pichon and Christelle Retière and Richard Redon and Alexander Pepler and Kirsty McWalter and Lydie Da Costa and Annick Toutain and Pierre Emmanuel Gleizes and Marc Baud'huin and Bertrand Isidor},
doi = {10.1016/j.ajhg.2019.09.024},
issn = {15376605},
year  = {2019},
date = {2019-01-01},
journal = {American Journal of Human Genetics},
volume = {105},
number = {5},
pages = {1040--1047},
abstract = {Variants in genes encoding ribosomal proteins have thus far been associated with Diamond-Blackfan anemia, a rare inherited bone marrow failure, and isolated congenital asplenia. Here, we report one de novo missense variant and three de novo splice variants in RPL13, which encodes ribosomal protein RPL13 (also called eL13), in four unrelated individuals with a rare bone dysplasia causing severe short stature. The three splice variants (c.477+1GtextgreaterT, c.477+1GtextgreaterA, and c.477+2 TtextgreaterC) result in partial intron retention, which leads to an 18-amino acid insertion. In contrast to observations from Diamond-Blackfan anemia, we detected no evidence of significant pre-rRNA processing disturbance in cells derived from two affected individuals. Consistently, we showed that the insertion-containing protein is stably expressed and incorporated into 60S subunits similar to the wild-type protein. Erythroid proliferation in culture and ribosome profile on sucrose gradient are modified, suggesting a change in translation dynamics. We also provide evidence that RPL13 is present at high levels in chondrocytes and osteoblasts in mouse growth plates. Taken together, we show that the identified RPL13 variants cause a human ribosomopathy defined by a rare skeletal dysplasia, and we highlight the role of this ribosomal protein in bone development.},
keywords = {bone dysplasia, chondrodysplasia, ribosome, RPL13, short stature, Spondyloepimetaphyseal dysplasia, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{Ghosh2019,
title = {EcRBPome: A comprehensive database of all known E. coli RNA-binding proteins},
author = {Pritha Ghosh and Adwait Joshi and Niang Guita and Bernard Offmann and Ramanathan Sowdhamini},
doi = {10.1186/s12864-019-5755-5},
issn = {14712164},
year  = {2019},
date = {2019-01-01},
journal = {BMC Genomics},
volume = {20},
number = {1},
pages = {1--6},
publisher = {BMC Genomics},
abstract = {The repertoire of RNA-binding proteins (RBPs) in bacteria play a crucial role in their survival, and interactions with the host machinery, but there is little information, record or characterisation in bacterial genomes. As a first step towards this, we have chosen the bacterial model system Escherichia coli, and organised all RBPs in this organism into a comprehensive database named EcRBPome. It contains RBPs recorded from 614 complete E. coli proteomes available in the RefSeq database (as of October 2018). The database provides various features related to the E. coli RBPs, like their domain architectures, PDB structures, GO and EC annotations etc. It provides the assembly, bioproject and biosample details of each strain, as well as cross-strain comparison of occurrences of various RNA-binding domains (RBDs). The percentage of RBPs, the abundance of the various RBDs harboured by each strain have been graphically represented in this database and available alongside other files for user download. To the best of our knowledge, this is the first database of its kind and we hope that it will be of great use to the biological community.},
keywords = {Cross-genome comparison, Database, Escherichia coli, Genome-wide survey, Pathotypes, Proteomes, RNA-binding proteins, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{10.1093/protein/gzz032,
title = {Toward the design of efficient transglycosidases: the case of the GH1 of Thermus thermophilus},
author = {Benoit David and Philippe Arnaud and Charles Tellier and Yves-Henri Sanejouand},
url = {https://doi.org/10.1093/protein/gzz032},
doi = {10.1093/protein/gzz032},
issn = {1741-0126},
year  = {2019},
date = {2019-01-01},
journal = {Protein Engineering, Design and Selection},
volume = {32},
number = {7},
pages = {309--316},
abstract = {Using the information available in the sequences of well-characterized transglycosidases found in plants, mutations were introduced in the glycoside hydrolase of the bacterium Thermus thermophilus, with the aim of turning it into an efficient transglycosidase. All mutants happen to have fair catalytic efficiencies, being at worst 25 times less efficient than the wild type. Noteworthy, W120F, one of our high transglycosylation yield (≈ 50%) mutants, is only two times less efficient than the wild type. Interestingly, while in the wild type the sidechain of the acid–base is only found able to sample a pair of equivalent conformations during 0.5-µs-long molecular dynamics simulations, its flexibility is much higher in the case of the high transglycosylation yield mutants. Our results thus suggest that engineering the flexibility of the acid–base of a retaining glycoside hydrolase could be a general way to turn it into an efficient transglycosidase.},
keywords = {team 1, team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Chaaya2019,
title = {Genetic background and immunological status influence B cell repertoire diversity in mice},
author = {Nancy Chaaya and Melody A Shahsavarian and Irene Maffucci and Alain Friboulet and Bernard Offmann and Jean Benoist Léger and Sylvain Rousseau and Bérang{è}re Avalle and Séverine Padiolleau-Lef{è}vre},
doi = {10.1038/s41598-019-50714-y},
issn = {20452322},
year  = {2019},
date = {2019-01-01},
journal = {Scientific Reports},
volume = {9},
number = {1},
pages = {1--7},
abstract = {The relationship between the immune repertoire and the physiopathological status of individuals is essential to apprehend the genesis and the evolution of numerous pathologies. Nevertheless, the methodological approaches to understand these complex interactions are challenging. We performed a study evaluating the diversity harbored by different immune repertoires as a function of their physiopathological status. In this study, we base our analysis on a murine scFv library previously described and representing four different immune repertoires: i) healthy and naïve, ii) healthy and immunized, iii) autoimmune prone and naïve, and iv) autoimmune prone and immunized. This library, 2.6 × 109 in size, is submitted to high throughput sequencing (Next Generation Sequencing, NGS) in order to analyze the gene subgroups encoding for immunoglobulins. A comparative study of the distribution of immunoglobulin gene subgroups present in the four libraries has revealed shifts in the B cell repertoire originating from differences in genetic background and immunological status of mice.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{Vetrivel2019,
title = {Structural variations within proteins can be as large as variations observed across their homologues},
author = {Iyanar Vetrivel and Alexandre G de Brevern and Frédéric Cadet and Narayanaswamy Srinivasan and Bernard Offmann},
doi = {10.1016/j.biochi.2019.09.013},
issn = {61831638},
year  = {2019},
date = {2019-01-01},
journal = {Biochimie},
volume = {167},
pages = {162--170},
abstract = {Understanding the structural plasticity of proteins is key to understanding the intricacies of their functions and mechanistic basis. In the current study, we analyzed the available multiple crystal structures of the same protein for the structural differences. For this purpose we used an abstraction of protein structures referred as Protein Blocks (PBs) that was previously established. We also characterized the nature of the structural variations for a few proteins using molecular dynamics simulations. In both the cases, the structural variations were summarized in the form of substitution matrices of PBs. We show that certain conformational states are preferably replaced by other specific conformational states. Interestingly, these structural variations are highly similar to those previously observed across structures of homologous proteins (r2 = 0.923) or across the ensemble of conformations from NMR data (r2 = 0.919). Thus our study quantitatively shows that overall trends of structural changes in a given protein are nearly identical to the trends of structural differences that occur in the topologically equivalent positions in homologous proteins. Specific case studies are used to illustrate the nature of these structural variations.},
keywords = {Molecular dynamics, Protein conformation, Protein structural variation, Structural alphabet, team 1, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Richoux2019,
title = {Comparing two deep learning sequence-based models for protein-protein interaction prediction},
author = {Florian Richoux and Charlène Servantie and Cynthia Borès and Stéphane Téletchéa},
url = {http://arxiv.org/abs/1901.06268},
year  = {2019},
date = {2019-01-01},
journal = {arXiv},
volume = {1901.06268},
abstract = {Biological data are extremely diverse, complex but also quite sparse. The recent developments in deep learning methods are offering new possibilities for the analysis of complex data. However, it is easy to be get a deep learning model that seems to have good results but is in fact either overfitting the training data or the validation data. In particular, the fact to overfit the validation data, called "information leak", is almost never treated in papers proposing deep learning models to predict protein-protein interactions (PPI). In this work, we compare two carefully designed deep learning models and show pitfalls to avoid while predicting PPIs through machine learning methods. Our best model predicts accurately more than 78% of human PPI, in very strict conditions both for training and testing. The methodology we propose here allow us to have strong confidences about the ability of a model to scale up on larger datasets. This would allow sharper models when larger datasets would be available, rather than current models prone to information leaks. Our solid methodological foundations shall be applicable to more organisms and whole proteome networks predictions.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@inproceedings{lva.20191097b,
title = {PBmapclust: Mapping and Clustering the Protein Conformational Space Using a Structural Alphabet},
author = {Iyanar Vetrivel and Lionel Hoffmann and Sean Guegan and Bernard Offmann and Adele D Laurent},
editor = {Jan Byska and Michael Krone and Björn Sommer},
doi = {10.2312/molva.20191097},
isbn = {978-3-03868-085-7},
year  = {2019},
date = {2019-01-01},
booktitle = {Workshop on Molecular Graphics and Visual Analysis of Molecular Data},
publisher = {The Eurographics Association},
abstract = {Analyzing the data from molecular dynamics simulation of biological macromolecules like proteins is challenging. We propose a simple tool called PBmapclust that is based on a well established structural alphabet called Protein blocks (PB). PBs help in tracing the trajectory of the protein backbone by categorizing it into 16 distinct structural states. PBmapclust provides a time vs. amino acid residue plot that is color coded to match each of the PBs. Color changes correspond to structural changes, giving a visual overview of the simulation. Further, PBmapclust enables the user to "map" the conformational space sampled by the protein during the MD simulation by clustering the conformations. The ability to generate sub-maps for specific residues and specific time intervals allows the user to focus on residues of interest like for active sites or disordered regions. We have included an illustrative case study to demonstrate the utility of the tool. It describes the effect of the disordered domain of a HSP90 co-chaperone on the conformation of its active site residues. The scripts required to perform PBmapclust are made freely available under the GNU general public license.},
keywords = {team 1, thesis},
pubstate = {published},
tppubtype = {inproceedings}
}
@incollection{liu2019pheromone,
title = {Pheromone, Natural Odor and Odorant Reception Suppressing Agent (ORSA) for Insect Control},
author = {Guoxia Liu and Philippe Arnaud and Bernard Offmann and Jean-François Picimbon},
doi = {10.1007/978-3-030-05165-5},
year  = {2019},
date = {2019-01-01},
booktitle = {Olfactory Concepts of Insect Control-Alternative to Insecticides},
pages = {311--345},
publisher = {Springer, Cham},
abstract = {Odorant-binding proteins (OBPs) are small ``bowl-like'' globular pro- teins, highly abundant in the antennae of most insect species. These proteins are believed to mediate reception of odor molecules at the periphery of sensory receptor neurons. Therefore, they may represent crucial targets for becoming new methods of insect pest control by directly interfering with the olfactory acuity of the insect. The current better understanding of molecular mechanisms underlying odor detec- tion and the knowledge about the functional binding sites of OBPs and many other families of binding proteins in various insect species is elucidated here. Such infor- mation forms the basis for the synthesis of new inhibitor olfactory compounds (Odorant Reception-Suppressing Agents, ORSAs) to interact specifically with the groups of insect pests.},
keywords = {team 1},
pubstate = {published},
tppubtype = {incollection}
}
@article{avEQ5:DELAVAT:2019aab,
title = {Transient Replication in Specialized Cells Favors Transfer of an Integrative and Conjugative Element},
author = {François Delavat and Roxane Moritz and Jan Roelof van der Meer},
doi = {10.1128/mBio.01133-19},
year  = {2019},
date = {2019-01-01},
journal = {mBio},
volume = {10},
number = {3},
abstract = {Integrative and conjugative elements (ICEs) are widespread mobile DNA within bacterial genomes, whose lifestyle is relatively poorly understood. ICEs transmit vertically through donor cell chromosome replication, but in order to transfer, they have to excise from the chromosome. The excision step makes ICEs prone to loss, in case the donor cell divides and the ICE is not replicated. By adapting the system of LacI-cyan fluorescent protein (CFP) binding to lacO operator arrays, we analyze here the process of excision and transfer of the ICE for 3-chlorobenzoate degradation (ICEclc) in individual cells of the bacterium Pseudomonas putida We provide evidence that ICEclc excises exclusively in a subset of specialized transfer-competent cells. ICEclc copy numbers in transfer-competent cells were higher than in regular nontransferring cells but were reduced in mutants lacking the ICE oriT1 origin of transfer, the ICE DNA relaxase, or the excision recombination sites. Consistently, transfer-competent cells showed a higher proportion without any observable LacI-CFP foci, suggesting ICEclc loss, but this proportion was independent of the ICE relaxase or the ICE origins of transfer. Our results thus indicated that the excised ICE becomes transiently replicated in transfer-competent cells, with up to six observable copies from LacI-CFP fluorescent focus measurements. Most of the observed ICEclc transfer to ICE-free P. putida recipients occurred from donors displaying 3 to 4 ICE copies, which constitute a minority among all transfer-competent cells. This finding suggests, therefore, that replication of the excised ICEclc in donors is beneficial for transfer fitness to recipient cells.IMPORTANCE Bacterial evolution is driven to a large extent by horizontal gene transfer (HGT)-the processes that distribute genetic material between species rather than by vertical descent. The different elements and processes mediating HGT have been characterized in great molecular detail. In contrast, very little is known on adaptive features selecting HGT evolvability and fitness optimization. By studying the molecular behavior of an integrated mobile DNA of the class of integrative and conjugative elements in individual Pseudomonas putida donor bacteria, we report here how transient replication of the element after its excision from the chromosome is favorable for its transfer success. Since successful transfer into a new recipient is a measure of the element's fitness, transient replication may have been selected as an adaptive benefit for more-optimal transfer.},
keywords = {Adaptation, chromosome replication, fitness, Horizontal gene transfer, origin of transfer, out_lab, Pseudomonas putida, single-cell studies, time-lapse microscopy, TraI relaxase},
pubstate = {published},
tppubtype = {article}
}
@article{EQ2:CAMBERLEIN:2019,
title = {Relative Contributions of Extracellular and Internalized Bacteria to Early Macrophage Proinflammatory Responses to Streptococcus pneumoniae},
author = {Jimstan Periselneris and Giuseppe Ercoli and Tracey Pollard and Suneeta Chimalapati and Emilie Camberlein and Gabriella Szylar and Catherine Hyams and Gillian Tomlinson and Fernanda C Petersen and Andres R Floto and Mahdad Noursadeghi and Jeremy S Brown},
editor = {Liise-anne Pirofski and Larry S McDaniel},
url = {https://mbio.asm.org/content/10/5/e02144-19},
doi = {10.1128/mBio.02144-19},
year  = {2019},
date = {2019-01-01},
journal = {mBio},
volume = {10},
number = {5},
publisher = {American Society for Microbiology},
abstract = {Both intracellular immune sensing and extracellular innate immune sensing have been implicated in initiating macrophage proinflammatory cytokine responses to Streptococcus pneumoniae. The S. pneumoniae capsule, a major virulence determinant, prevents phagocytosis, and we hypothesized that this would reduce activation of host innate inflammatory responses by preventing activation of intracellular proinflammatory signaling pathways. We investigated this hypothesis in human monocyte-derived macrophages stimulated with encapsulated or isogenic unencapsulated mutant S. pneumoniae. Unexpectedly, despite strongly inhibiting bacterial internalization, the capsule resulted in enhanced inflammatory cytokine production by macrophages infected with S. pneumoniae. Experiments using purified capsule material and a Streptococcus mitis mutant expressing an S. pneumoniae serotype 4 capsule indicated these differences required whole bacteria and were not due to proinflammatory effects of the capsule itself. Transcriptional profiling demonstrated relatively few differences in macrophage gene expression profiles between infections with encapsulated S. pneumoniae and those with unencapsulated S. pneumoniae, largely limited to reduced expression of proinflammatory genes in response to unencapsulated bacteria, predicted to be due to reduced activation of the NF-κB family of transcription factors. Blocking S. pneumoniae internalization using cytochalasin D had minimal effects on the inflammatory response to S. pneumoniae. Experiments using murine macrophages indicated that the affected genes were dependent on Toll-like receptor 2 (TLR2) activation, although not through direct stimulation of TLR2 by capsule polysaccharide. Our data demonstrate that the early macrophage proinflammatory response to S. pneumoniae is mainly dependent on extracellular bacteria and reveal an unexpected proinflammatory effect of encapsulated S. pneumoniae that could contribute to disease pathogenesis.IMPORTANCE Multiple extra- and intracellular innate immune receptors have been identified that recognize Streptococcus pneumoniae, but the relative contributions of intra- versus extracellular bacteria to the inflammatory response were unknown. We have shown that intracellular S. pneumoniae contributes surprisingly little to the inflammatory responses, with production of important proinflammatory cytokines largely dependent on extracellular bacteria. Furthermore, although we expected the S. pneumoniae polysaccharide capsule to block activation of the host immune system by reducing bacterial internalization and therefore activation of intracellular innate immune receptors, there was an increased inflammatory response to encapsulated compared to unencapsulated bacteria, which is likely to contribute to disease pathogenesis.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{EQ2:LAMBERT:2019,
title = {Physiological and genetic changes during natural senescence of Medicago truncatula root nodules},
author = {Sarra El Msehli and Annie Lambert and Julie Hopkins and Eric Boncompagni and Samira Smiti-Aschi and Didier Hérouart and Pierre Frendo},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/jpln.201800233},
doi = {10.1002/jpln.201800233},
year  = {2019},
date = {2019-01-01},
journal = {Journal of Plant Nutrition and Soil Science},
volume = {182},
number = {3},
pages = {385-392},
abstract = {Abstract Under nitrogen-limiting conditions, legumes are able to form a symbiotic interaction with bacteria of the Rhizobiaceae family to produce root nodules. These new root organs satisfy plant nitrogen needs by reducing atmospheric nitrogen to ammonium. However, the senescence of these organs disturbs the assimilation of nitrogen. In this study, we present different histological, biochemical, and genetic markers of the natural nodule senescence in Medicago truncatula over a 10-week period following bacterial inoculation. During aging the length and the weight of nodules increased, whereas the nitrogen-fixing capacity of the nodules decreased. The development of the nodule senescence zone correlated with a reduction in leghemoglobin levels without significant reduction in the total protein concentration of the nodule. In contrast, no difference in glutathione and homoglutathione concentration was detected at the onset of senescence at 6 and 8 weeks after bacterial infection. Furthermore, we observed a significant decrease in the relative transcription levels of Nodule Cysteine Rich 001, MtLb1, sucrose synthase 1, thioredoxin S1 and thioredoxin S2 genes, which are involved in nodule development and functioning, thus demonstrating that natural senescence impacts the transcription of genes involved in the expansion and the metabolism of the nitrogen-fixing zone. Finally, the induction of amine oxidase and cysteine protease CP6 transcription was unstable, suggesting that these two genes are related to senescence but are not robust gene markers of the natural senescence process. Considered together, our results define novel biochemical and genetic markers for natural nodule senescence and show that leghemoglobin gene transcription and protein concentration are robust markers that closely correlate with nitrogen fixation efficiency.},
keywords = {biological nitrogen fixation, leghemoglobin, Medicago truncatula, natural nodule senescence, nodule gene expression, out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{EQ4:DUC:2019c,
title = {How well do RNA-Seq differential gene expression tools perform in a complex eukaryote? A case study in Arabidopsis thaliana},
author = {Kimon Froussios and Nick J Schurch and Katarzyna Mackinnon and Marek Gierliṅski and Céline Duc and Gordon G Simpson and Geoffrey J Barton},
url = {https://doi.org/10.1093/bioinformatics/btz089},
doi = {10.1093/bioinformatics/btz089},
issn = {1367-4803},
year  = {2019},
date = {2019-01-01},
journal = {Bioinformatics},
volume = {35},
number = {18},
pages = {3372-3377},
abstract = {RNA-seq experiments are usually carried out in three or fewer replicates. In order to work well with so few samples, differential gene expression (DGE) tools typically assume the form of the underlying gene expression distribution. In this paper, the statistical properties of gene expression from RNA-seq are investigated in the complex eukaryote, Arabidopsis thaliana, extending and generalizing the results of previous work in the simple eukaryote Saccharomyces cerevisiae.We show that, consistent with the results in S.cerevisiae, more gene expression measurements in A.thaliana are consistent with being drawn from an underlying negative binomial distribution than either a log-normal distribution or a normal distribution, and that the size and complexity of the A.thaliana transcriptome does not influence the false positive rate performance of nine widely used DGE tools tested here. We therefore recommend the use of DGE tools that are based on the negative binomial distribution.The raw data for the 17 WT Arabidopsis thaliana datasets is available from the European Nucleotide Archive (E-MTAB-5446). The processed and aligned data can be visualized in context using IGB (Freese et al., 2016), or downloaded directly, using our publicly available IGB quickload server at https://compbio.lifesci.dundee.ac.uk/arabidopsisQuickload/public_quickload/ under ^a€˜RNAseq&gt;Froussios2019^a€texttrademark. All scripts and commands are available from github at https://github.com/bartongroup/KF_arabidopsis-GRNA.Supplementary data are available at Bioinformatics online.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{EQ4:DUC:2019b,
title = {Replication-coupled histone H3.1 deposition determines nucleosome composition and heterochromatin dynamics during Arabidopsis seedling development},
author = {Matthias Benoit and Lauriane Simon and Sophie Desset and Céline Duc and Sylviane Cotterell and Axel Poulet and Samuel Le Goff and Christophe Tatout and Aline V Probst},
url = {https://nph.onlinelibrary.wiley.com/doi/abs/10.1111/nph.15248},
doi = {10.1111/nph.15248},
year  = {2019},
date = {2019-01-01},
journal = {New Phytologist},
volume = {221},
number = {1},
pages = {385-398},
abstract = {Summary Developmental phase transitions are often characterized by changes in the chromatin landscape and heterochromatin reorganization. In Arabidopsis, clustering of repetitive heterochromatic loci into so-called chromocenters is an important determinant of chromosome organization in nuclear space. Here, we investigated the molecular mechanisms involved in chromocenter formation during the switch from a heterotrophic to a photosynthetically competent state during early seedling development. We characterized the spatial organization and chromatin features at centromeric and pericentromeric repeats and identified mutant contexts with impaired chromocenter formation. We find that clustering of repetitive DNA loci into chromocenters takes place in a precise temporal window and results in reinforced transcriptional repression. Although repetitive sequences are enriched in H3K9me2 and linker histone H1 before repeat clustering, chromocenter formation involves increasing enrichment in H3.1 as well as H2A.W histone variants, hallmarks of heterochromatin. These processes are severely affected in mutants impaired in replication-coupled histone assembly mediated by CHROMATIN ASSEMBLY FACTOR 1 (CAF-1). We further reveal that histone deposition by CAF-1 is required for efficient H3K9me2 enrichment at repetitive sequences during chromocenter formation. Taken together, we show that chromocenter assembly during post-germination development requires dynamic changes in nucleosome composition and histone post-translational modifications orchestrated by the replication-coupled H3.1 deposition machinery.},
keywords = {Arabidopsis thaliana, CAF-1, Chromatin, development, epigenetics, histone variant, out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid31078733,
title = {Tumor vasculature remodeling by radiation therapy increases doxorubicin distribution and efficacy},
author = {Vincent Potiron and Karen Clément-Colmou and Emmanuel Jouglar and Manon Pietri and Sophie Chiavassa and Grégory Delpon and François Paris and Stéphane Supiot},
doi = {10.1016/j.canlet.2019.05.005},
issn = {1872-7980},
year  = {2019},
date = {2019-01-01},
urldate = {2019-01-01},
journal = {Cancer Lett},
volume = {457},
pages = {1--9},
abstract = {The tumor microenvironment regulates cancer initiation, progression and response to treatment. In particular, the immature tumor vasculature may impede drugs from reaching tumor cells at a lethal concentration. We and others have shown that radiation therapy (RT) induces pericyte recruitment, resembling vascular normalization. Here, we asked whether radiation-induced vascular remodeling translates into improved tissue distribution and efficacy of chemotherapy. First, RT induced vascular remodeling, accompanied by decreased hypoxia and/or increased Hoechst perfusion in prostate PC3 and LNCaP and Lewis lung carcinoma. These results were independent of the RT regimen, respectively 10 × 2 Gy and 2 × 12 Gy, suggesting a common effect. Next, using doxorubicin as a fluorescent reporter, we observed that RT improves intra-tumoral chemotherapy distribution. These effects were not hindered by anti-angiogenic sunitinib. Moreover, sub-optimal doses of doxorubicin had almost no effect alone, but significantly delayed tumor growth after RT. These data demonstrate that RT favors the efficacy of chemotherapy by improving tissue distribution, and could be an alternative chemosensitizing strategy.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid30300771,
title = {Management of non-metastatic castrate-resistant prostate cancer: A systematic review},
author = {Yohann Loriot and Stéphane Supiot and Jean-Baptiste Beauval and Friederike Schlürmann and Gilles Pasticier and Paul Sargos and Philippe Barthélémy and Géraldine Pignot and Denis Maillet and Sébastien Vincendeau and Emmanuel Gross and Guillaume Ploussard and Marc-Olivier Timsit and Delphine Borchiellini},
doi = {10.1016/j.ctrv.2018.09.006},
issn = {1532-1967},
year  = {2018},
date = {2018-11-01},
urldate = {2018-11-01},
journal = {Cancer Treat Rev},
volume = {70},
pages = {223--231},
abstract = {Management of non metastatic castrate resistant prostate cancer is challenging for clinicians due to the heterogeneity of the disease and to the scarce clinical data available in this setting. Recent results obtained with the new generation hormone therapies (NGHT) apalutamide and enzalutamide bring a new perspective for the treatment strategy. The authors present here a systematic review of the treatment options.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Frioux2018,
title = {Scalable and exhaustive screening of metabolic functions carried out by microbial consortia},
author = {Clémence Frioux and Enora Fremy and Camille Trottier and Anne Siegel},
url = {https://academic.oup.com/bioinformatics/article/34/17/i934/5093211},
doi = {10.1093/bioinformatics/bty588},
issn = {1367-4803},
year  = {2018},
date = {2018-09-01},
journal = {Bioinformatics},
volume = {34},
number = {17},
pages = {i934--i943},
publisher = {Oxford University Press},
abstract = {Motivation. The selection of species exhibiting metabolic behaviors of interest is a challenging step when switching from the investigation of a large microbiota to the study of functions effectiveness. Approaches based on a compartmentalized framework are not scalable. The output of scalable approaches based on a non-compartmentalized modeling may be so large that it has neither been explored nor handled so far. 
Results. We present the Miscoto tool to facilitate the selection of a community optimizing a desired function in a microbiome by reporting several possibilities which can be then sorted according to biological criteria. Communities are exhaustively identified using logical programming and by combining the non-compartmentalized and the compartmentalized frameworks. The benchmarking of 4.9 million metabolic functions associated with the Human Microbiome Project, shows that Miscoto is suited to screen and classify metabolic producibility in terms of feasibility, functional redundancy and cooperation processes involved. As an illustration of a host-microbial system, screening the Recon 2.2 human metabolism highlights the role of different consortia within a family of 773 intestinal bacteria. 
Availability and implementation. Miscoto source code, instructions for use and examples are available at: https://github.com/cfrioux/miscoto.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid29860350,
title = {Potential contribution of strigolactones in regulating scion growth and branching in grafted grapevine in response to nitrogen availability},
author = {Noé Cochetel and Eloïse Météier and Isabelle Merlin and Cyril Hévin and Jean-Bernard Pouvreau and Pierre Coutos-Thévenot and Michel Hernould and Philippe Vivin and Sarah Jane Cookson and Nathalie Ollat and Virginie Lauvergeat},
doi = {10.1093/jxb/ery206},
issn = {1460-2431},
year  = {2018},
date = {2018-07-01},
urldate = {2018-07-01},
journal = {J Exp Bot},
volume = {69},
number = {16},
pages = {4099--4112},
abstract = {In grafted plants, rootstocks assure the mineral nutrition of the scion and modify its development. In this study, we show that two grapevine rootstock genotypes have different shoot branching architectures when cultivated as cuttings and that this trait is transmitted to the scion when grafted. Shoot branching plasticity in response to nitrogen supply was also studied. As strigolactones are known to have a role in the regulation of shoot development in response to nutrient availability, their involvement in the control of scion architecture by the rootstock was investigated. Functional characterization of putative grapevine strigolactone biosynthetic genes in Arabidopsis mutants or grapevine cell suspensions showed similar functions to those of Arabidopsis. Both rootstocks produced strigolactone-like compounds; the quantity produced in response to nitrogen treatments differed between the two rootstock genotypes and correlated with the expression of putative strigolactone biosynthetic genes. Exudation of strigolactone-like compounds by both rootstocks was closely related to the developmental pattern of the scion in grafted plants. These results suggest that differential regulation of strigolactone biosynthesis in response to nitrogen availability may contribute to the control of scion development conferred by each rootstock genotype.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Aite2018,
title = {Traceability, reproducibility and wiki-exploration for “à-la-carte” reconstructions of genome-scale metabolic models},
author = {Méziane Aite and Marie Chevallier and Clémence Frioux and Camille Trottier and Jeanne Got and Maria Paz Cortés and Sebastiàn N Mendoza and Grégory Carrier and Olivier Dameron and Nicolas Guillaudeux and Mauricio Latorre and Nicolàs Loira and Gabriel V Markov and Alejandro Maass and Anne Siegel},
editor = {Jens Nielsen},
url = {http://dx.plos.org/10.1371/journal.pcbi.1006146},
doi = {10.1371/journal.pcbi.1006146},
issn = {1553-7358},
year  = {2018},
date = {2018-05-01},
journal = {PLOS Computational Biology},
volume = {14},
number = {5},
pages = {e1006146},
publisher = {Public Library of Science},
abstract = {Genome-scale metabolic models have become the tool of choice for the global analysis of microorganism metabolism, and their reconstruction has attained high standards of quality and reliability. Improvements in this area have been accompanied by the development of some major platforms and databases, and an explosion of individual bioinformatics methods. Consequently, many recent models result from “à la carte” pipelines, combining the use of platforms, individual tools and biological expertise to enhance the quality of the reconstruction. Although very useful, introducing heterogeneous tools, that hardly interact with each other, causes loss of traceability and reproducibility in the reconstruction process. This represents a real obstacle, especially when considering less studied species whose metabolic reconstruction can greatly benefit from the comparison to good quality models of related organisms. This work proposes an adaptable workspace, AuReMe, for sustainable reconstructions or improvements of genome-scale metabolic models involving personalized pipelines. At each step, relevant information related to the modifications brought to the model by a method is stored. This ensures that the process is reproducible and documented regardless of the combination of tools used. Additionally, the workspace establishes a way to browse metabolic models and their metadata through the automatic generation of ad-hoc local wikis dedicated to monitoring and facilitating the process of reconstruction. AuReMe supports exploration and semantic query based on RDF databases. We illustrate how this workspace allowed handling, in an integrated way, the metabolic reconstructions of non-model organisms such as an extremophile bacterium or eukaryote algae. Among relevant applications, the latter reconstruction led to putative evolutionary insights of a metabolic pathway.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{avEQ5:Nomaguchi_TIRICHINE:2018,
title = {Homoeolog expression bias in allopolyploid oleaginous marine diatom Fistulifera solaris},
author = {Tatsuhiro Nomaguchi and Yoshiaki Maeda and Tomoko Yoshino and Toru Asahi and Leila Tirichine and Chris Bowler and Tsuyoshi Tanaka},
url = {https://doi.org/10.1186%2Fs12864-018-4691-0},
doi = {10.1186/s12864-018-4691-0},
year  = {2018},
date = {2018-05-01},
journal = {BMC Genomics},
volume = {19},
number = {1},
publisher = {Springer Science and Business Media LLC},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid29506537,
title = {A mini-review of quality of life as an outcome in prostate cancer trials: patient-centered approaches are needed to propose appropriate treatments on behalf of patients},
author = {Yohann Foucher and Marine Lorent and Philippe Tessier and Stéphane Supiot and Véronique Sébille and Etienne Dantan},
doi = {10.1186/s12955-018-0870-6},
issn = {1477-7525},
year  = {2018},
date = {2018-03-01},
urldate = {2018-03-01},
journal = {Health Qual Life Outcomes},
volume = {16},
number = {1},
pages = {40},
abstract = {BACKGROUND: Patients with prostate cancer (PC) may be ready to make trade-offs between their quantity and their quality of life. For instance, elderly patients may prefer the absence of treatment if it is associated with a low-risk of disease progression, compared to treatments aiming at preventing disease progression but with a substantial deterioration of their Health-Related Quality of Life (HRQoL). Therefore, it seems relevant to compare the treatments by considering both survival and HRQoL. In this mini-review, the aim was to question whether the potential trade-offs between survival and HRQoL are considered in high impact factor journals.

METHODS: The study was conducted from the PubMed database for recent papers published between May 01, 2013, and May 01, 2015. We also restricted our search to nine medical journals with 2013 impact factor &gt; 15.

RESULTS: Among the 30 selected studies, only six collected individual HRQoL as a secondary endpoint by using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. In four studies, the time to HRQoL change was analyzed, but its definitions varied. In two studies, the mean changes in HRQoL between the baseline and the 12- or 16-week follow-up were analyzed. None of the six studies reported in a single endpoint both the quantity and the quality of life.

CONCLUSIONS: Our mini-review, which only focused on recent publications in journals with high-impact, suggests moving PC clinical research towards patient-centered outcomes-based studies. This may help physicians to propose the most appropriate treatment on behalf of patients. We recommend the use of indicators such as Quality-Adjusted Life-Years (QALYs) as principal endpoint in future clinical trials.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{avEQ5:Rastogi_TIRICHINE:2018,
title = {Integrative analysis of large scale transcriptome data draws a comprehensive landscape of Phaeodactylum tricornutum, genome and evolutionary origin of diatoms},
author = {Achal Rastogi and Uma Maheswari and Richard G Dorrell and Fabio Rocha Jimenez Vieira and Florian Maumus and Adam Kustka and James McCarthy and Andy E Allen and Paul Kersey and Chris Bowler and Leila Tirichine},
url = {https://doi.org/10.1038%2Fs41598-018-23106-x},
doi = {10.1038/s41598-018-23106-x},
year  = {2018},
date = {2018-03-01},
journal = {Scientific Reports},
volume = {8},
number = {1},
publisher = {Springer Science and Business Media LLC},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid29515786,
title = {Evaluation of tumor hypoxia prior to radiotherapy in intermediate-risk prostate cancer using F-fluoromisonidazole PET/CT: a pilot study},
author = {Stéphane Supiot and Caroline Rousseau and Mélanie Dore and Catherine Cheze-Le-Rest and Christine Kandel-Aznar and Vincent Potiron and Stéphane Guerif and François Paris and Ludovic Ferrer and Loïc Campion and Philippe Meingan and Gregory Delpon and Mathieu Hatt and Dimitris Visvikis},
doi = {10.18632/oncotarget.24234},
issn = {1949-2553},
year  = {2018},
date = {2018-02-01},
urldate = {2018-02-01},
journal = {Oncotarget},
volume = {9},
number = {11},
pages = {10005--10015},
abstract = {Purpose: Hypoxia is a major factor in prostate cancer aggressiveness and radioresistance. Predicting which patients might be bad candidates for radiotherapy may help better personalize treatment decisions in intermediate-risk prostate cancer patients. We assessed spatial distribution of F-Misonidazole (FMISO) PET/CT uptake in the prostate prior to radiotherapy treatment.

Materials and Methods: Intermediate-risk prostate cancer patients about to receive high-dose (&gt;74 Gy) radiotherapy to the prostate without hormonal treatment were prospectively recruited between 9/2012 and 10/2014. Prior to radiotherapy, all patients underwent a FMISO PET/CT as well as a MRI and F-choline-PET. F-choline and FMISO-positive volumes were semi-automatically determined using the fuzzy locally adaptive Bayesian (FLAB) method. In FMISO-positive patients, a dynamic analysis of early tumor uptake was performed. Group differences were assessed using the Wilcoxon signed rank test. Parameters were correlated using Spearman rank correlation.

Results: Of 27 patients (median age 76) recruited to the study, 7 and 9 patients were considered positive at 2.5h and 3.5h FMISO PET/CT respectively. Median SUV and SUV tumor to muscle (T/M) ratio were respectively 3.4 and 3.6 at 2.5h, and 3.2 and 4.4 at 3.5h. The median FMISO-positive volume was 1.1 ml.

Conclusions: This is the first study regarding hypoxia imaging using FMISO in prostate cancer showing that a small FMISO-positive volume was detected in one third of intermediate-risk prostate cancer patients.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid29482652,
title = {A new tissue segmentation method to calculate 3D dose in small animal radiation therapy},
author = {C Noblet and G Delpon and S Supiot and V Potiron and F Paris and S Chiavassa},
doi = {10.1186/s13014-018-0971-8},
issn = {1748-717X},
year  = {2018},
date = {2018-02-01},
urldate = {2018-02-01},
journal = {Radiat Oncol},
volume = {13},
number = {1},
pages = {32},
abstract = {BACKGROUND: In pre-clinical animal experiments, radiation delivery is usually delivered with kV photon beams, in contrast to the MV beams used in clinical irradiation, because of the small size of the animals. At this medium energy range, however, the contribution of the photoelectric effect to absorbed dose is significant. Accurate dose calculation therefore requires a more detailed tissue definition because both density (ρ) and elemental composition (Z) affect the dose distribution. Moreover, when applied to cone beam CT (CBCT) acquisitions, the stoichiometric calibration of HU becomes inefficient as it is designed for highly collimated fan beam CT acquisitions. In this study, we propose an automatic tissue segmentation method of CBCT imaging that assigns both density (ρ) and elemental composition (Z) in small animal dose calculation.

METHODS: The method is based on the relationship found between CBCT number and ρ*Z product computed from known materials. Monte Carlo calculations were performed to evaluate the impact of ρZ variation on the absorbed dose in tissues. These results led to the creation of a tissue database composed of artificial tissues interpolated from tissue values published by the ICRU. The ρZ method was validated by measuring transmitted doses through tissue substitute cylinders and a mouse with EBT3 film. Measurements were compared to the results of the Monte Carlo calculations.

RESULTS: The study of the impact of ρZ variation over the range of materials, from ρZ = 2 g.cm (lung) to 27 g.cm (cortical bone) led to the creation of 125 artificial tissues. For tissue substitute cylinders, the use of ρZ method led to maximal and average relative differences between the Monte Carlo results and the EBT3 measurements of 3.6% and 1.6%. Equivalent comparison for the mouse gave maximal and average relative differences of 4.4% and 1.2%, inside the 80% isodose area. Gamma analysis led to a 94.9% success rate in the 10% isodose area with 4% and 0.3 mm criteria in dose and distance.

CONCLUSIONS: Our new tissue segmentation method was developed for 40kVp CBCT images. Both density and elemental composition are assigned to each voxel by using a relationship between HU and the product ρZ. The method, validated by comparing measurements and calculations, enables more accurate small animal dose distribution calculated on low energy CBCT images.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1021/acs.nanolett.8b02717,
title = {Mechanical Vibrations of Atomically Defined Metal Clusters: From Nano- to Molecular-Size Oscillators},
author = {Paolo Maioli and Tatjana Stoll and Huziel E Sauceda and Israel Valencia and Aude Demessence and Franck Bertorelle and Aurélien Crut and Fabrice Vallée and Ignacio L Garzón and Giulio Cerullo and Natalia Del Fatti},
url = {https://doi.org/10.1021/acs.nanolett.8b02717},
doi = {10.1021/acs.nanolett.8b02717},
year  = {2018},
date = {2018-01-01},
journal = {Nano Letters},
volume = {18},
number = {11},
pages = {6842-6849},
abstract = {Acoustic vibrations of small nanoparticles are still ruled by continuum mechanics laws down to diameters of a few nanometers. The elastic behavior at lower sizes (&lt;1–2 nm), where nanoparticles become molecular clusters made by few tens to few atoms, is still little explored. The question remains to which extent the transition from small continuous-mass solids to discrete-atom molecular clusters affects their specific low-frequency vibrational modes, whose period is classically expected to linearly scale with diameter. Here, we investigate experimentally by ultrafast time-resolved optical spectroscopy the acoustic response of atomically defined ligand-protected metal clusters Aun(SR)m with a number n of atoms ranging from 10 to 102 (0.5–1.5 nm diameter range). Two periods, corresponding to fundamental breathing- and quadrupolar-like acoustic modes, are detected, with the latter scaling linearly with cluster diameters and the former taking a constant value. Theoretical calculations based on density functional theory (DFT) predict in the case of bare clusters vibrational periods scaling with size down to diatomic molecules. For ligand-protected clusters, they show a pronounced effect of the ligand molecules on the breathing-like mode vibrational period at the origin of its constant value. This deviation from classical elasticity predictions results from mechanical mass-loading effects due to the protecting layer. This study shows that clusters characteristic vibrational frequencies are compatible with extrapolation of continuum mechanics model down to few atoms, which is in agreement with DFT computations.},
note = {PMID: 30247927},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1021/acsomega.8b02615,
title = {Isomeric Effect of Mercaptobenzoic Acids on the Synthesis, Stability, and Optical Properties of Au25(MBA)18 Nanoclusters},
author = {Franck Bertorelle and Isabelle Russier-Antoine and Clothilde Comby-Zerbino and Fabien Chirot and Philippe Dugourd and Pierre-François Brevet and Rodolphe Antoine},
url = {https://doi.org/10.1021/acsomega.8b02615},
doi = {10.1021/acsomega.8b02615},
year  = {2018},
date = {2018-01-01},
journal = {ACS Omega},
volume = {3},
number = {11},
pages = {15635-15642},
abstract = {We report a simple size focusing, two-step “bottom-up” protocol to prepare water-soluble Au25(MBA)18 nanoclusters, using the three isomers of mercaptobenzoic acids (p/m/o-MBA) as capping ligands and Me3NBH3 as a mild reducing agent. The relative stability of the gas-phase multiply deprotonated Au25(MBA)18 ions was investigated by collision-induced dissociation. This permitted us to evaluate the possible isomeric effect on the Au–S interfacial bond stress. We also investigated their optical properties. The absorption spectra of Au25(MBA)18 isomers were very similar and showed bands at 690, 470, and 430 nm. For all Au25(MBA)18 isomeric clusters, no measurable one-photon excited fluorescence under UV–vis light was found, in neither solid- nor solution-state. The two-photon excited emission spectra and first hyperpolarizabilities of the clusters were also determined. The results are discussed in terms of the possible isomeric effect on excitations within the metal core and the possibility of charge transfer excitations from the ligands to the metal nanocluster.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{C8NR00660A,
title = {pH-Induced transformation of ligated Au25 to brighter Au23 nanoclusters},
author = {Magdalena Waszkielewicz and Joanna Olesiak-Banska and Clothilde Comby-Zerbino and Franck Bertorelle and Xavier Dagany and Ashu K Bansal and Muhammad T Sajjad and Ifor D W Samuel and Zeljka Sanader and Miroslawa Rozycka and Magdalena Wojtas and Katarzyna Matczyszyn and Vlasta Bonacic-Koutecky and Rodolphe Antoine and Andrzej Ozyhar and Marek Samoc},
url = {http://dx.doi.org/10.1039/C8NR00660A},
doi = {10.1039/C8NR00660A},
year  = {2018},
date = {2018-01-01},
journal = {Nanoscale},
volume = {10},
pages = {11335-11341},
publisher = {The Royal Society of Chemistry},
abstract = {Thiolate-protected gold nanoclusters have recently attracted considerable attention due to their size-dependent luminescence characterized by a long lifetime and large Stokes shift. However, the optimization of nanocluster properties such as the luminescence quantum yield is still a challenge. We report here the transformation of Au25Capt18 (Capt labels captopril) nanoclusters occurring at low pH and yielding a product with a much increased luminescence quantum yield which we have identified as Au23Capt17. We applied a simple method of treatment with HCl to accomplish this transformation and we characterized the absorption and emission of the newly created ligated nanoclusters as well as their morphology. Based on DFT calculations we show which Au nanocluster size transformations can lead to highly luminescent species such as Au23Capt17.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1021/acs.jpcc.8b03550,
title = {Nonlinear Refraction and Absorption of Ag29 Nanoclusters: Evidence for Two-Photon Absorption Saturation},
author = {Albert S Reyna and Isabelle Russier-Antoine and Franck Bertorelle and Emmanuel Benichou and Philippe Dugourd and Rodolphe Antoine and Pierre-François Brevet and Cid B de Araújo},
url = {https://doi.org/10.1021/acs.jpcc.8b03550},
doi = {10.1021/acs.jpcc.8b03550},
year  = {2018},
date = {2018-01-01},
journal = {The Journal of Physical Chemistry C},
volume = {122},
number = {32},
pages = {18682-18689},
abstract = {We report the nonlinear absorption and refraction of Ag29 nanocluster aqueous suspensions using the open and closed aperture Z-scan method at 532 nm. The stoichiometry of the atomically precise silver nanoclusters has been determined by mass spectrometry, and their formula is Ag29DHLA12 where the ligand is dihydrolipoic acid (DHLA). Using different concentration of nanoclusters, we observe beyond the expected linear absorption saturation and nonlinear absorption a clear saturation of the nonlinear absorption, a feature so far not described for nanoclusters. The nonlinear refraction is also determined and exhibits a regular behavior with a negative n2 value. A figure of merit is discussed in view of potential applications.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{SOLEILHAC2018283,
title = {Sizing protein-templated gold nanoclusters by time resolved fluorescence anisotropy decay measurements},
author = {Antonin Soleilhac and Franck Bertorelle and Rodolphe Antoine},
url = {https://www.sciencedirect.com/science/article/pii/S138614251730999X},
doi = {https://doi.org/10.1016/j.saa.2017.12.025},
issn = {1386-1425},
year  = {2018},
date = {2018-01-01},
journal = {Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy},
volume = {193},
pages = {283-288},
abstract = {Protein-templated gold nanoclusters (AuNCs) are very attractive due to their unique fluorescence properties. A major problem however may arise due to protein structure changes upon the nucleation of an AuNC within the protein for any future use as in vivo probes, for instance. In this work, we propose a simple and reliable fluorescence based technique measuring the hydrodynamic size of protein-templated gold nanoclusters. This technique uses the relation between the time resolved fluorescence anisotropy decay and the hydrodynamic volume, through the rotational correlation time. We determine the molecular size of protein-directed AuNCs, with protein templates of increasing sizes, e.g. insulin, lysozyme, and bovine serum albumin (BSA). The comparison of sizes obtained by other techniques (e.g. dynamic light scattering and small-angle X-ray scattering) between bare and gold clusters containing proteins allows us to address the volume changes induced either by conformational changes (for BSA) or the formation of protein dimers (for insulin and lysozyme) during cluster formation and incorporation.},
keywords = {Fluorescence anisotropy, Gold nanoclusters, Oligomers, out_lab, Proteins, Size, Unfolding},
pubstate = {published},
tppubtype = {article}
}
@article{comby2018structural,
title = {Structural insights into glutathione-protected gold Au 10- 12 (SG) 10- 12 nanoclusters revealed by ion mobility mass spectrometry},
author = {Clothilde Comby-Zerbino and Franck Bertorelle and Fabien Chirot and Philippe Dugourd and Rodolphe Antoine},
url = {https://doi.org/10.1140/epjd/e2018-90133-8},
doi = {10.1140/epjd/e2018-90133-8},
year  = {2018},
date = {2018-01-01},
journal = {The European Physical Journal D},
volume = {72},
number = {8},
pages = {1--5},
publisher = {Springer},
abstract = {Gold nanoclusters protected by ligands present well-defined compositions and tunable structures, which builds a solid basis for correlation between structures and properties. We report a combined ion mobility-mass spectrometry approach for the analysis of ultra-small gold nanoclusters protected by glutathione (SG) as ligand molecules, Au10−12(SG)10−12. Collision cross section (CCS) measurements are reported for different charge states for Au10(SG)10, Au11(SG)11 and Au12(SG)12 nanoclusters. Computational calculations, at the PM7 semi-empirical level of theory, are performed to optimize geometrical structures and use them to compute CCS. The comparison of the experimentally and theoretically determined CCS allows drawing conclusions on the structural changes, in particular partial unfolding of SG ligands, upon charging.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{bertorelle2018bulky,
title = {Bulky Counterions: Enhancing the Two-Photon Excited Fluorescence of Gold Nanoclusters},
author = {Franck Bertorelle and Christophe Moulin and Antonin Soleilhac and Clothilde Comby-Zerbino and Philippe Dugourd and Isabelle Russier-Antoine and Pierre-François Brevet and Rodolphe Antoine},
url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cphc.201701186},
doi = {https://doi.org/10.1002/cphc.201701186},
year  = {2018},
date = {2018-01-01},
journal = {ChemPhysChem},
volume = {19},
number = {2},
pages = {165-168},
abstract = {Abstract Increasing fluorescence quantum yields of ligand-protected gold nanoclusters has attracted wide research interest. The strategy consisting in using bulky counterions has been found to dramatically enhance the fluorescence. In this Communication, we push forward this concept to the nonlinear optical regime. We show that by an appropriate choice of bulky counterions and of solvent, a 30-fold increase in two-photon excited fluorescence (TPEF) signal at ≈600 nm for gold nanoclusters can be obtained. This would correspond to a TPEF cross-section in the range of 0.1 to 1 GM.},
keywords = {glutathione, gold clusters, luminescence, multiphoton imaging, two-photon absorption},
pubstate = {published},
tppubtype = {article}
}
@article{sanejouand2018density,
title = {Has the density of sources of gamma-ray burts been constant over the last ten billion years ?},
author = {Yves-Henri Sanejouand},
url = {https://arxiv.org/abs/1803.05303},
year  = {2018},
date = {2018-01-01},
journal = {arXiv:1803.05303},
abstract = {A generic tired-light mechanism is examined in which a photon, like any particle moving in a medium, experiences friction, that is, a force resisting its motion. If the velocity of light is assumed to be constant, this hypothesis yields a Hubble-like law which is also a consequence of the Rh = ct cosmology. Herein, it is used for estimating matter density as a function of redshift, allowing to show that the density of sources of long gamma-ray bursts appears to be nearly constant, up to z ≈ 4. Assuming that the later is a fair probe of the former, this means that matter density has been roughly constant over the last ten billion years, implying that, at least over this period, matter has been in an overall state of equilibrium.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{TENSAOUTI201812,
title = {19 Is dose escalation in intracranial pediatric ependymoma feasible with advanced radiation techniques?},
author = {F Tensaouti and A Ducassou and S Bolle and JL Habrand and C Alapetite and B Coche-Dequeant and V Bernier and L Claude and C Carrie and L Padovani and X Muracciole and S Supiot and A Huchet and J Leseur and C Kerr and G Hangard and A Lisbona and F Goudjil and R Ferrand and A Laprie},
url = {https://www.sciencedirect.com/science/article/pii/S1120179718311943},
doi = {https://doi.org/10.1016/j.ejmp.2018.09.032},
issn = {1120-1797},
year  = {2018},
date = {2018-01-01},
urldate = {2018-01-01},
journal = {Physica Medica},
volume = {56},
pages = {12},
note = {Abstracts of the 57èmes Journées Scientifiques de la Société Française de Physique Médicale},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@incollection{cEQ4:THIRIET:2018,
title = {Nuclear Dynamics at Specific Cell Cycle Stages in the Slime Mold emphPhysarum polycephalum},
author = {Christophe Thiriet},
editor = {Christophe Lavelle and Jean-Marc Victor},
url = {http://www.sciencedirect.com/science/article/pii/B9780128034804000247},
doi = {https://doi.org/10.1016/B978-0-12-803480-4.00024-7},
issn = {25425358},
year  = {2018},
date = {2018-01-01},
urldate = {2018-01-01},
booktitle = {Nuclear Architecture and Dynamics},
volume = {2},
pages = {557 - 567},
publisher = {Academic Press},
address = {Boston},
series = {Translational Epigenetics},
abstract = {The genetic activities require the alteration of chromatin structures. This involves movements of nucleosomes that make accessible the genetic information. Understanding the mechanisms of chromatin activities, the roles of histone domains and modifications in vivo are important tasks. The slime mold Physarum polycephalum is a powerful model system with millions of naturally synchronous nuclei and the unique capability to spontaneously internalize exogenous proteins. The present chapter describes the life cycle of the myxomycete and provides examples of analyses of chromatin dynamics in replication and in transcription.},
keywords = {chromatin assembly, chromatin dynamics, histones, Nucleus},
pubstate = {published},
tppubtype = {incollection}
}
@article{DELAVAT20181,
title = {Rapid and efficient protocol to introduce exogenous DNA in Vibrio harveyi and Pseudoalteromonas sp.},
author = {François Delavat and Adeline Bidault and Vianney Pichereau and Christine Paillard},
url = {https://www.sciencedirect.com/science/article/pii/S0167701218306870},
doi = {https://doi.org/10.1016/j.mimet.2018.09.022},
issn = {0167-7012},
year  = {2018},
date = {2018-01-01},
journal = {Journal of Microbiological Methods},
volume = {154},
pages = {1-5},
abstract = {Vibrio campbellii BAA-1116 is renowned for its bioluminescence properties, and genetic tools are available to genetically track this strain. However, many other ecologically important V. harveyi strains exist, for which only few genetic tools are available. In this study, a rapid electroporation protocol was developed to transform replicative plasmids in various environmental V. harveyi and Pseudoalteromonas strains. Moreover, a mini-Tn7 delivery system was modified to site-specifically integrate mini-transposons in the genome of V. harveyi ORM4. As a proof-of-principle, replicative plasmids carrying bioreporters were introduced by electroporation in V. harveyi ORM4 cells, and gene expression was followed at the single cell level. We could demonstrate that a flagellar gene is subjected to bimodal gene expression in V. harveyi ORM4, being highly expressed in 10% of the population in stationary phase. This study extends the possibilities to study environmental Vibrio strains and uncovers the occurrence of phenotypic heterogeneity in flagellar expression in Vibrio.},
keywords = {Bioreporter, Electroporation, Flagellum expression, Mini-transposon, out_lab, phenotypic heterogeneity},
pubstate = {published},
tppubtype = {article}
}
@article{palve2018detection,
title = {Detection of high-risk human papillomavirus in oral cavity squamous cell carcinoma using multiple analytes and their role in patient survival},
author = {Vinayak Palve and Jamir Bagwan and Neeraja M Krishnan and Manisha Pareek and Udita Chandola and Amritha Suresh and Gangotri Siddappa and Bonney L James and Vikram Kekatpure and Moni Abraham Kuriakose and others},
doi = {10.1200/JGO.18.00058},
year  = {2018},
date = {2018-01-01},
journal = {Journal of global oncology},
volume = {4},
pages = {1--33},
publisher = {American Society of Clinical Oncology},
abstract = {Purpose. Accurate detection of human papillomavirus (HPV) in oral cavity squamous cell carcinoma (OSCC) is essential to understanding the role of HPV in disease prognosis and management of patients. We used different analytes and methods to understand the true prevalence of HPV in a cohort of patients with OSCC with different molecular backgrounds, and we correlated HPV data with patient survival. 
 Methods. We integrated data from multiple analytes (HPV DNA, HPV RNA, and p16), assays (immunohistochemistry, polymerase chain reaction [PCR], quantitative PCR [qPCR], and digital PCR), and molecular changes (somatic mutations and DNA methylation) from 153 patients with OSCC to correlate p16 expression, HPV DNA, and HPV RNA with HPV incidence and patient survival. 
 Results. High prevalence (33% to 58%) of HPV16/18 DNA did not correlate with the presence of transcriptionally active viral genomes (15%) in tumors. Eighteen percent of the tumors were p16 positive and only 6% were both HPV DNA and HPV RNA positive. Most tumors with relatively high copy number HPV DNA and/or HPV RNA, but not with HPV DNA alone (irrespective of copy number), were wild-type for TP53 and CASP8 genes. In our study, p16 protein, HPV DNA, and HPV RNA, either alone or in combination, did not correlate with patient survival. Nine HPV-associated genes stratified the virus-positive from the virus-negative tumor group with high confidence (P &lt; .008) when HPV DNA copy number and/or HPV RNA were considered to define HPV positivity, and not HPV DNA alone, irrespective of copy number (P &lt; .2). 
 Conclusion. In OSCC, the presence of both HPV RNA and p16 is rare. HPV DNA alone is not an accurate measure of HPV positivity and therefore may not be informative. HPV DNA, HPV RNA, and p16 do not correlate with patients’ outcome.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{li2018genome,
title = {Genome-Wide RNAi Screen Identify Melanoma-Associated Antigen Mageb3 Involved in X Chromosome Inactivation},
author = {Wei Li and Ru Hong and Lan-Tian Lai and Qiman Dong and Peiling Ni and Rosi Chelliah and Mehnaz Huq and Siti Nadirah Binte Ismail and Udita Chandola and Zhiwei Ang and others},
doi = {10.1016/j.jmb.2018.05.031},
year  = {2018},
date = {2018-01-01},
journal = {Journal of molecular biology},
volume = {430},
number = {17},
pages = {2734--2746},
publisher = {Elsevier},
abstract = {Xist (inactivated X chromosome specific transcript) is a prototype long noncoding RNA in charge of epigenetic silencing of one X chromosome in each female cell in mammals. In a genetic screen, we identify Mageb3 and its homologs Mageb1 and Mageb2 as genes functionally required for Xist-mediated gene silencing. Mageb1–3 are previously uncharacterized genes belonging to the MAGE (melanoma-associated antigen) gene family. Mageb1–3 are expressed in undifferentiated ES cells and early stages of in vitro differentiation, a critical time window of X chromosome inactivation. Mageb3 showed both cytoplasmic and nuclear localization without enrichment on the inactive X (Xi). Mageb3 interacted with Polycomb group ring finger 3 (Pcgf3), a RING finger protein involved in recruiting Polycomb activities onto Xi. Mageb3 overexpression stabilized Pcgf3 protein. Mageb1–3 gene knockout affected H3K27me3 enrichment and the spreading of gene silencing along Xi. These data suggested that Mageb3 might regulate the recruitment of the Polycomb complex onto Xi and subsequent H3K27me3 modification through Pcgf3. Moreover, the nucleolar enrichment of Mageb3 was diminished when nuclear matrix factor hnRNP U is overexpressed, implying the interaction between Mageb3 and nuclear matrix, which is another possible mechanism for Mageb3 to regulate X chromosome inactivation.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@incollection{THIRIET2018557,
title = {25 - Nuclear Dynamics at Specific Cell Cycle Stages in the Slime Mold Physarum polycephalum},
author = {Christophe Thiriet},
editor = {Christophe Lavelle and Jean-Marc Victor},
url = {http://www.sciencedirect.com/science/article/pii/B9780128034804000247},
doi = {https://doi.org/10.1016/B978-0-12-803480-4.00024-7},
issn = {25425358},
year  = {2018},
date = {2018-01-01},
booktitle = {Nuclear Architecture and Dynamics},
volume = {2},
pages = {557--567},
publisher = {Academic Press},
address = {Boston},
series = {Translational Epigenetics},
abstract = {The genetic activities require the alteration of chromatin structures. This involves movements of nucleosomes that make accessible the genetic information. Understanding the mechanisms of chromatin activities, the roles of histone domains and modifications in vivo are important tasks. The slime mold Physarum polycephalum is a powerful model system with millions of naturally synchronous nuclei and the unique capability to spontaneously internalize exogenous proteins. The present chapter describes the life cycle of the myxomycete and provides examples of analyses of chromatin dynamics in replication and in transcription.},
keywords = {chromatin assembly, chromatin dynamics, histones, Nucleus},
pubstate = {published},
tppubtype = {incollection}
}
@inproceedings{dion2018,
title = {Design and screening of sugar-derived small molecule inhibitors of galectins.},
author = {Johann Dion and Nataliya Storozhylova and S Dahbi and Annie Lambert and Stéphane Téletchéa and Christophe Dussouy and Cyrille Grandjean},
year  = {2018},
date = {2018-01-01},
booktitle = {J. Protein Proteomics},
journal = {J. Protein Proteomics},
volume = {9},
keywords = {team 2, thesis},
pubstate = {published},
tppubtype = {inproceedings}
}
@article{10.1093/nar/gky1257,
title = {A novel Staphylococcus aureus cis–trans type I toxin–antitoxin module with dual effects on bacteria and host cells},
author = {Noëlla Germain-Amiot and Yoann Augagneur and Emilie Camberlein and Irène Nicolas and Valérie Lecureur and Astrid Rouillon and Brice Felden},
url = {https://doi.org/10.1093/nar/gky1257},
doi = {10.1093/nar/gky1257},
issn = {0305-1048},
year  = {2018},
date = {2018-01-01},
journal = {Nucleic Acids Research},
volume = {47},
number = {4},
pages = {1759-1773},
abstract = {Bacterial type I toxin–antitoxin (TA) systems are widespread, and consist of a stable toxic peptide whose expression is monitored by a labile RNA antitoxin. We characterized Staphylococcus aureus SprA2/SprA2AS module, which shares nucleotide similarities with the SprA1/SprA1AS TA system. We demonstrated that SprA2/SprA2AS encodes a functional type I TA system, with the cis-encoded SprA2AS antitoxin acting in trans to prevent ribosomal loading onto SprA2 RNA. We proved that both TA systems are distinct, with no cross-regulation between the antitoxins in vitro or in vivo. SprA2 expresses PepA2, a toxic peptide which internally triggers bacterial death. Conversely, although PepA2 does not affect bacteria when it is present in the extracellular medium, it is highly toxic to other host cells such as polymorphonuclear neutrophils and erythrocytes. Finally, we showed that SprA2AS expression is lowered during osmotic shock and stringent response, which indicates that the system responds to specific triggers. Therefore, the SprA2/SprA2AS module is not redundant with SprA1/SprA1AS, and its PepA2 peptide exhibits an original dual mode of action against bacteria and host cells. This suggests an altruistic behavior for S. aureus in which clones producing PepA2 in vivo shall die as they induce cytotoxicity, thereby promoting the success of the community.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@inbook{groisillier2018cloning,
title = {Cloning and expression strategies for the post-genomic analysis of brown algae},
author = {Agnès Groisillier},
editor = {Bénédicte Charrier and Thomas Wichard and C R K Reddy},
doi = {https://doi.org/10.1201/b21460},
isbn = {9781498796422},
year  = {2018},
date = {2018-01-01},
booktitle = {Protocols for Macroalgae Research},
journal = {Protocols for macroalgae research},
pages = {453--468},
publisher = {CRC Press},
chapter = {30},
abstract = {The production of stable and soluble proteins is one of the most important steps before structural and functional studies of biological importance. An alternative to obtaining native enzymes is the purification of recombinant enzymes after expression of genes of interest in a heterologous host, in particular the bacteria Escherichia coli. One of the advantages of this approach is to quickly produce bacterial biomass likely to contain the proteins of interest. This protocol describes the different steps to cloning, expression, and purification of protein identified in the brown alga Ectocarpus siliculosus.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {inbook}
}
@article{Benhelli-Mokrani2018,
title = {Genome-wide identification of genic and intergenic neuronal DNA regions bound by Tau protein under physiological and stress conditions},
author = {Houda Benhelli-Mokrani and Zeyni Mansuroglu and Alban Chauderlier and Benoit Albaud and David Gentien and Sabrina Sommer and Claire Schirmer and Lucie Laqueuvre and Thibaut Josse and Luc Buée and Bruno Lefebvre and Marie Christine Galas and Sylvie Sou{è}s and Eliette Bonnefoy},
doi = {10.1093/nar/gky929},
issn = {13624962},
year  = {2018},
date = {2018-01-01},
journal = {Nucleic acids research},
volume = {46},
number = {21},
pages = {11405--11422},
abstract = {Tauopathies such as Alzheimer's Disease (AD) are neurodegenerative disorders for which there is presently no cure. They are named after the abnormal oligomerization/aggregation of the neuronal microtubule-associated Tau protein. Besides its role as a microtubule-associated protein, a DNA-binding capacity and a nuclear localization for Tau protein has been described in neurons. While questioning the potential role of Tau-DNA binding in the development of tauopathies, we have carried out a large-scale analysis of the interaction of Tau protein with the neuronal genome under physiological and heat stress conditions using the ChIP-on-chip technique that combines Chromatin ImmunoPrecipitation (ChIP) with DNA microarray (chip). Our findings show that Tau protein specifically interacts with genic and intergenic DNA sequences of primary culture of neurons with a preference for DNA regions positioned beyond the ±5000 bp range from transcription start site. An AG-rich DNA motif was found recurrently present within Tau-interacting regions and 30% of Tau-interacting regions overlapped DNA sequences coding for lncRNAs. Neurological processes affected in AD were enriched among Tau-interacting regions with in vivo gene expression assays being indicative of a transcriptional repressor role for Tau protein, which was exacerbated in neurons displaying nuclear pathological oligomerized forms of Tau protein.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Deriabin2018,
title = {Similar nature leads to improved properties: Cyclic organosilicon triperoxides as promising curing agents for liquid polysiloxanes},
author = {Konstantin V Deriabin and Ivan A Yaremenko and Mikhail V Chislov and Fabrice Fleury and Alexander O Terent'Ev and Regina M Islamova},
doi = {10.1039/c8nj02499e},
issn = {13699261},
year  = {2018},
date = {2018-01-01},
journal = {New Journal of Chemistry},
volume = {42},
number = {18},
pages = {15006--15013},
publisher = {Royal Society of Chemistry},
abstract = {Cyclic organosilicon triperoxides were found to be vinyl-selective free-radical initiators for thermal curing at 100-180 °C of vinyl-terminated polydimethylsiloxane and trimethylsilyl-terminated polymethylhydrosiloxane producing homogeneous transparent silicone rubbers with antibacterial properties. The usage of the cyclic organosilicon triperoxides as the curing agents does not require free radical inhibitors in comparison with diacyl- and dialkyl peroxides. Among the tested compounds, the peroxide with the Me-Si-Me fragment and two cyclohexane rings is a much more active curing agent (180 °C},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Lafont2018,
title = {Assessment of DNA-PKcs kinase activity by quantum dot–based microarray},
author = {Florian Lafont and Nizar Ayadi and Cathy Charlier and Pierre Weigel and Igor Nabiev and Houda Benhelli-Mokrani and Fabrice Fleury},
doi = {10.1038/s41598-018-29256-2},
issn = {20452322},
year  = {2018},
date = {2018-01-01},
journal = {Scientific Reports},
volume = {8},
number = {1},
pages = {1--12},
abstract = {Therapeutic efficacy against cancer is often based on a variety of DNA lesions, including DNA double-strand breaks (DSBs) which are repaired by homologous recombination and non-homologous end joining (NHEJ) pathways. In the past decade, the functions of the DNA repair proteins have been described as a potential mechanism of resistance in tumor cells. Therefore, the DNA repair proteins have become targets to improve the efficacy of anticancer therapy. Given the central role of DNA-PKcs in NHEJ, the therapeutic efficacy of targeting DNA-PKcs is frequently described as a strategy to prevent repair of treatment-induced DNA damage in cancer cells. The screening of a new inhibitor acting as a sensitizer requires the development of a high-throughput tool in order to identify and assess the most effective molecule. Here, we describe the elaboration of an antibody microarray dedicated to the NHEJ pathway that we used to evaluate the DNA-PKcs kinase activity in response to DNA damage. By combining a protein microarray with Quantum-Dot detection, we show that it is possible to follow the modification of phosphoproteomic cellular profiles induced by inhibitors during the response to DNA damage. Finally, we discuss the promising tool for screening kinase inhibitors and targeting DSB repair to improve cancer treatment.},
keywords = {impact, team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{cadet2018application,
title = {Application of fourier transform and proteochemometrics principles to protein engineering},
author = {Frédéric Cadet and Nicolas Fontaine and Iyanar Vetrivel and Matthieu Ng Fuk Chong and Olivier Savriama and Xavier Cadet and Philippe Charton},
doi = {10.1186/s12859-018-2407-8},
year  = {2018},
date = {2018-01-01},
journal = {BMC bioinformatics},
volume = {19},
number = {1},
pages = {1--11},
publisher = {BioMed Central},
abstract = {Connecting the dots between the protein sequence and its function is of fundamental interest for protein engineers. In-silico methods are useful in this quest especially when structural information is not available. In this study we propose a mutant library screening tool called iSAR (innovative Sequence Activity Relationship) that relies on the physicochemical properties of the amino acids, digital signal processing and partial least squares regression to uncover these sequence-function correlations.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Thiriet-Rupert2018,
title = {Identification of transcription factors involved in the phenotype of a domesticated oleaginous microalgae strain of Tisochrysis lutea},
author = {S Thiriet-Rupert and G Carrier and Camille Trottier and D Eveillard and B Schoefs and G Bougaran and J -P Cadoret and B Chénais and B Saint-Jean},
doi = {10.1016/j.algal.2017.12.011},
issn = {22119264},
year  = {2018},
date = {2018-01-01},
journal = {Algal Research},
volume = {30},
abstract = {Microalgae are an outstanding source of high value products with applications in food, feed or biofuel production. Among these promising organisms, the haptophyte Tisochrysis lutea is commonly used as a feed for shellfish and shrimps in aquaculture. Its capacity to produce high amounts of docosahexanoic acid and storage lipids is also of economic interest for nutrition and energy production. Consequently, understanding its lipid accumulation under nitrogen deprivation is of major interest. Here, we aimed to identify Transcription Factors (TFs) involved in the establishment of the mutant phenotype of the 2Xc1 strain of T. lutea, which accumulates double the quantity of storage lipids under nitrogen deprivation than the wild type strain (WTc1). Strains were grown in chemostats and subjected to different nitrogen availability (limitation, repletion and depletion). Using RNA-seq data, the differentially expressed genes (DEGs) between strains were identified and summarized as a co-expression network to pinpoint putative major TFs in mutant phenotypes. This analysis was followed by a complementary Weighted Gene Correlation Network Analysis in order to classify genes based on their relative importance to mutant phenotype features, regardless of annotation biases due to the lack of functional annotation of the Tisochrysis lutea draft genome. This network-like strategy allowed the identification of seven TF candidates related to key functions in the mutant strain compared with WTc1. In particular, MYB-2R_14 and NF-YB_2 TFs are related to photosynthesis, oxidative stress response and triacylglycerol synthesis. GATA_2, MYB-rel_11 and MYB-2R_20 TFs are likely to be related to nitrogen uptake or carbon and nitrogen recycling, feeding carbohydrate synthesis in the form of chrysolaminarin. Finally, a q-RT-PCR approach further characterized the role of MYB-rel_11 and MYB-2R_20, revealing an expression pattern dependent on nitrogen availability.},
keywords = {Algae, Carbohydrates, Gene co-expression network, lipids, out_lab, Tisochrysis lutea, Transcription factor},
pubstate = {published},
tppubtype = {article}
}
@article{Jaunet-Lahary2018,
title = {Computational simulations determining disulfonic stilbene derivative bioavailability within human serum albumin},
author = {Titouan Jaunet-Lahary and Daniel P Vercauteren and Fabrice Fleury and Adèle D Laurent},
doi = {10.1039/c8cp00704g},
issn = {14639076},
year  = {2018},
date = {2018-01-01},
journal = {Physical Chemistry Chemical Physics},
volume = {20},
number = {26},
pages = {18020--18030},
publisher = {Royal Society of Chemistry},
abstract = {Disulfonic stilbene (DS) derivatives are a member of the large family of compounds widely employed in medicine and biology as modulators for membrane transporters or inhibitors of a protein involved in DNA repair. They constitute interesting compounds that have not yet been investigated within the bioavailability framework. No crystallographic structures exist involving such compounds embedded in the most common drug carrier, human serum albumin (HSA). The present work studies, for the first time, the physico-chemical features driving the inclusion of three DS derivatives (amino, nitro and acetamido, named DADS, DNDS and DATDS, respectively) within the four common HSA binding sites using combined molecular docking and molecular dynamics simulations. A careful analysis of each ligand within each of the studied binding sites is carried out, highlighting specific interactions and key residues playing a role in stabilizing the ligand within each pocket. The comparison between DADS, DNDS and DATDS reveals that depending on the binding site, the conclusions are rather different. For instance, the IB binding site shows a specificity to DADS compounds while IIIA is the most favorable site for DNDS and DATDS. 2018},
keywords = {team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{RN5,
title = {Seed germination in parasitic plants: what insights can we expect from strigolactone research?},
author = {Guillaume Brun and Lukas Braem and Séverine Thoiron and Kris Gevaert and Sophie Goormachtig and Philippe Delavault},
url = {https://watermark.silverchair.com/erx472.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAt4wggLaBgkqhkiG9w0BBwagggLLMIICxwIBADCCAsAGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM1yniRk8_noMBOyNMAgEQgIICkQSx0NkVWTLILIUWSlmnkftHgPP-m5t-cQPJknvKituLwilM0lvjYzZ8hS9XgfOcZXtWI5s8xbpatlB8cdpZP9UIDbsBGHsUHt7S7HlpuAZMTQ45haVuNqJvyuKge5jMk7hS88X3g81iv7EI3sBpzHd2YIKMfNhaf48kbTwwrzS4DRYGNAvL4WBc-raLQpiuWzkwcigfD-aABZkBD1-gFe8IEUnOb2RkmjlUr_liOJU7PFy_Cx4vIQEP2JYFSTWPLCUjkUom_5WQQc6OEtCE9DM41tXRLSckgbL81--d43m9Fej8gsZ4BfyxtqW2HQeS-iOmIDEWFFSwij_htBntsNJyL2q_vklyiqNPmXnr7aAG5USvV7SKNyBXBLiZMhcK4LNAPAEXOmSdSzYuMfXoO0kbljSM6ht_Z5lxwGuDDEByCqSieqyirwwsSP5G7zjEwBgLyWku3qPSVQlSht3Zw5syxIR8XT1sWmvYDcKEttmpmlsNbJCFK8vfRSi8KeAAbs1zSzg17FzgpZCOkqRY5GKdESZfeVuNdyzEA5rlbuLLEKwV2LRm2RAg8b2ygsderPTNrSDDfwLwbN5VRWZF7lyhSHemRqDOnYU59ezeS882026E4kS2LpG_zwSjma0HyCHEE2GNywtVrwKfa_0_gKE1Q-OQ8INzeshP-lrHHZqa8Q4bZLCQXLfyE1qlJnLTroDX4UIpRRhA1Ildrf_lGv2vFlPxs9DzFqjLPoqsmb5cBVdv819hiJTgqzR4v-Nm2sw1H5Vp2V8l6aPIab9ijg3ZIlpm-B6VUnUsjZA5gxKdSDHHZzIQluh9wxsUc6c_WYBWNA20_EOSP9ALg-sQsplZk3VAb1WhQh7antobYSAx_A},
doi = {10.1093/jxb/erx472},
issn = {0022-0957},
year  = {2018},
date = {2018-01-01},
urldate = {2018-01-01},
journal = {J Exp Bot},
volume = {69},
number = {9},
pages = {2265-2280},
abstract = {Obligate root-parasitic plants belonging to the Orobanchaceae family are deadly pests for major crops all over the world. Because these heterotrophic plants severely damage their hosts even before emerging from the soil, there is an unequivocal need to design early and efficient methods for their control. The germination process of these species has probably undergone numerous selective pressure events in the course of evolution, in that the perception of host-derived molecules is a necessary condition for seeds to germinate. Although most of these molecules belong to the strigolactones, structurally different molecules have been identified. Since strigolactones are also classified as novel plant hormones that regulate several physiological processes other than germination, the use of autotrophic model plant species has allowed the identification of many actors involved in the strigolactone biosynthesis, perception, and signal transduction pathways. Nevertheless, many questions remain to be answered regarding the germination process of parasitic plants. For instance, how did parasitic plants evolve to germinate in response to a wide variety of molecules, while autotrophic plants do not? What particular features are associated with their lack of spontaneous germination? In this review, we attempt to illustrate to what extent conclusions from research into strigolactones could be applied to better understand the biology of parasitic plants.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Cadet2018,
title = {A machine learning approach for reliable prediction of amino acid interactions and its application in the directed evolution of enantioselective enzymes},
author = {Frédéric Cadet and Nicolas Fontaine and Guangyue Li and Joaquin Sanchis and Matthieu {Ng Fuk Chong} and Rudy Pandjaitan and Iyanar Vetrivel and Bernard Offmann and Manfred T Reetz},
doi = {10.1038/s41598-018-35033-y},
issn = {20452322},
year  = {2018},
date = {2018-01-01},
journal = {Scientific Reports},
volume = {8},
number = {1},
pages = {1--15},
abstract = {Directed evolution is an important research activity in synthetic biology and biotechnology. Numerous reports describe the application of tedious mutation/screening cycles for the improvement of proteins. Recently, knowledge-based approaches have facilitated the prediction of protein properties and the identification of improved mutants. However, epistatic phenomena constitute an obstacle which can impair the predictions in protein engineering. We present an innovative sequence-activity relationship (innov'SAR) methodology based on digital signal processing combining wet-lab experimentation and computational protein design. In our machine learning approach, a predictive model is developed to find the resulting property of the protein when the n single point mutations are permuted (2n combinations). The originality of our approach is that only sequence information and the fitness of mutants measured in the wet-lab are needed to build models. We illustrate the application of the approach in the case of improving the enantioselectivity of an epoxide hydrolase from Aspergillus niger. n = 9 single point mutants of the enzyme were experimentally assessed for their enantioselectivity and used as a learning dataset to build a model. Based on combinations of the 9 single point mutations (29), the enantioselectivity of these 512 variants were predicted, and candidates were experimentally checked: better mutants with higher enantioselectivity were indeed found.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{pmid28976545,
title = {A novel, smaller scaffold for Affitins: Showcase with binders specific for EpCAM},
author = {Valentina Kalichuk and Axelle Renodon-Cornière and Ghislaine Béhar and Federico Carrión and Gonzalo Obal and Mike Maillasson and Barbara Mouratou and Véronique Préat and Frédéric Pecorari},
doi = {10.1002/bit.26463},
issn = {1097-0290},
year  = {2018},
date = {2018-01-01},
urldate = {2018-01-01},
journal = {Biotechnol Bioeng},
volume = {115},
number = {2},
pages = {290--299},
abstract = {Affitins are highly stable engineered affinity proteins, originally derived from Sac7d and Sso7d, two 7 kDa DNA-binding polypeptides from Sulfolobus genera. Their efficiency as reagents for intracellular targeting, enzyme inhibition, affinity purification, immunolocalization, and various other applications has been demonstrated. Recently, we have characterized the 7 kDa DNA-binding family, and Aho7c originating from Acidianus hospitalis was shown to be its smallest member with thermostability comparable to those of Sac7d and Sso7d. Here, after four rounds of selection by ribosome display against the human recombinant Epithelial Cell Adhesion Molecule (hrEpCAM), we obtained novel Aho7c-based Affitins. The binders were expressed in soluble form in Escherichia coli, displayed high stability (up to 74°C; pH 0-12) and were shown to be specific for the hrEpCAM extracellular domain with picomolar affinities (K  = 110 pM). Thus, we propose Aho7c as a good candidate for the creation of Affitins with a 10% smaller size than the Sac7d-based ones (60 vs. 66 amino acids).},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{avEQ5:DELAVAT:2018aab,
title = {Rapid and efficient protocol to introduce exogenous DNA in emphVibrio harveyi and emphPseudoalteromonas sp},
author = {François Delavat and Adeline Bidault and Vianney Pichereau and Christine Paillard},
doi = {10.1016/j.mimet.2018.09.022},
year  = {2018},
date = {2018-01-01},
journal = {J Microbiol Methods},
volume = {154},
pages = {1-5},
abstract = {Vibrio campbellii BAA-1116 is renowned for its bioluminescence properties, and genetic tools are available to genetically track this strain. However, many other ecologically important V. harveyi strains exist, for which only few genetic tools are available. In this study, a rapid electroporation protocol was developed to transform replicative plasmids in various environmental V. harveyi and Pseudoalteromonas strains. Moreover, a mini-Tn7 delivery system was modified to site-specifically integrate mini-transposons in the genome of V. harveyi ORM4. As a proof-of-principle, replicative plasmids carrying bioreporters were introduced by electroporation in V. harveyi ORM4 cells, and gene expression was followed at the single cell level. We could demonstrate that a flagellar gene is subjected to bimodal gene expression in V. harveyi ORM4, being highly expressed in 10% of the population in stationary phase. This study extends the possibilities to study environmental Vibrio strains and uncovers the occurrence of phenotypic heterogeneity in flagellar expression in Vibrio.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
@article{EQ2:CAMBERLEIN:2018,
title = {A novel Staphylococcus aureus cis-trans type I toxin-antitoxin module with dual effects on bacteria and host cells},
author = {Noëlla Germain-Amiot and Yoann Augagneur and Emilie Camberlein and Irène Nicolas and Valérie Lecureur and Astrid Rouillon and Brice Felden},
url = {https://doi.org/10.1093/nar/gky1257},
doi = {10.1093/nar/gky1257},
issn = {0305-1048},
year  = {2018},
date = {2018-01-01},
journal = {Nucleic Acids Research},
volume = {47},
number = {4},
pages = {1759-1773},
abstract = {Bacterial type I toxin^a€``antitoxin (TA) systems are widespread, and consist of a stable toxic peptide whose expression is monitored by a labile RNA antitoxin. We characterized Staphylococcus aureus SprA2/SprA2AS module, which shares nucleotide similarities with the SprA1/SprA1AS TA system. We demonstrated that SprA2/SprA2AS encodes a functional type I TA system, with the cis-encoded SprA2AS antitoxin acting in trans to prevent ribosomal loading onto SprA2 RNA. We proved that both TA systems are distinct, with no cross-regulation between the antitoxins in vitro or in vivo. SprA2 expresses PepA2, a toxic peptide which internally triggers bacterial death. Conversely, although PepA2 does not affect bacteria when it is present in the extracellular medium, it is highly toxic to other host cells such as polymorphonuclear neutrophils and erythrocytes. Finally, we showed that SprA2AS expression is lowered during osmotic shock and stringent response, which indicates that the system responds to specific triggers. Therefore, the SprA2/SprA2AS module is not redundant with SprA1/SprA1AS, and its PepA2 peptide exhibits an original dual mode of action against bacteria and host cells. This suggests an altruistic behavior for S.^A aureus in which clones producing PepA2 in vivo shall die as they induce cytotoxicity, thereby promoting the success of the community.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{avEQ5:Carradec_TIRICHINE:2018,
title = {A global ocean atlas of eukaryotic genes},
author = {Quentin Carradec and Eric and Pelletier and Corinne Da Silva and Adriana Alberti and Yoann Seeleuthner and Romain Blanc-Mathieu and Gipsi Lima-Mendez and Fabio Rocha and Leila Tirichine and Karine Labadie and Amos Kirilovsky and Alexis Bertrand and Stefan Engelen and Mohammed-Amin Madoui and Raphaël Méheust and Julie Poulain and Sarah Romac and Daniel J Richter and Genki Yoshikawa and Céline Dimier and Stefanie Kandels-Lewis and Marc Picheral and Sarah Searson and Olivier Jaillon and Jean-Marc Aury and Eric Karsenti and Matthew B Sullivan and Shinichi Sunagawa and Peer Bork and Fabrice Not and Pascal Hingamp and Jeroen Raes and Lionel Guidi and Hiroyuki Ogata and Colomban de Vargas and Daniele Iudicone and Chris Bowler and Patrick Wincker},
url = {https://doi.org/10.1038%2Fs41467-017-02342-1},
doi = {10.1038/s41467-017-02342-1},
year  = {2018},
date = {2018-01-01},
journal = {Nature Communications},
volume = {9},
number = {1},
publisher = {Springer Science and Business Media LLC},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Bertorelle_2017,
title = {Bulky Counterions: Enhancing the Two-Photon Excited Fluorescence of Gold Nanoclusters},
author = {Franck Bertorelle and Christophe Moulin and Antonin Soleilhac and Clothilde Comby-Zerbino and Philippe Dugourd and Isabelle Russier-Antoine and Pierre-François Brevet and Rodolphe Antoine},
url = {http://dx.doi.org/10.1002/cphc.201701186},
doi = {10.1002/cphc.201701186},
issn = {1439-4235},
year  = {2017},
date = {2017-12-01},
journal = {ChemPhysChem},
volume = {19},
number = {2},
pages = {165–168},
publisher = {Wiley},
abstract = {Increasing fluorescence quantum yields of ligand-protected gold nanoclusters has attracted wide research interest. The strategy consisting in using bulky counterions has been found to dramatically enhance the fluorescence. In this communication, we push forward this concept to the nonlinear optical regime. We show that by an appropriate choice of bulky counterions and of solvent, a 30-fold increase in two-photon excited fluorescence (TPEF) signal at ~600 nm for gold nanoclusters can be obtained. This would correspond to a TPEF cross section in the range of 0.1 to 1 GM.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Vetrivel2017,
title = {Knowledge-based prediction of protein backbone conformation using a structural alphabet},
author = {Iyanar Vetrivel and Swapnil Mahajan and Manoj Tyagi and Lionel Hoffmann and Yves-Henri Sanejouand and Narayanaswamy Srinivasan and Alexandre G {De Brevern} and Frédéric Cadet and Bernard Offmann},
doi = {10.1371/journal.pone.0186215},
issn = {19326203},
year  = {2017},
date = {2017-11-01},
journal = {PLoS ONE},
volume = {12},
number = {11},
publisher = {Public Library of Science},
abstract = {Libraries of structural prototypes that abstract protein local structures are known as structural alphabets and have proven to be very useful in various aspects of protein structure analyses and predictions. One such library, Protein Blocks, is composed of 16 standard 5-residues long structural prototypes. This form of analyzing proteins involves drafting its structure as a string of Protein Blocks. Predicting the local structure of a protein in terms of protein blocks is the general objective of this work. A new approach, PB-kPRED is proposed towards this aim. It involves (i) organizing the structural knowledge in the form of a database of pentapeptide fragments extracted from all protein structures in the PDB and (ii) applying a knowledge-based algorithm that does not rely on any secondary structure predictions and/ or sequence alignment profiles, to scan this database and predict most probable backbone conformations for the protein local structures. Though PB-kPRED uses the structural information from homologues in preference, if available. The predictions were evaluated rigorously on 15,544 query proteins representing a non-redundant subset of the PDB filtered at 30% sequence identity cut-off. We have shown that the kPRED method was able to achieve mean accuracies ranging from 40.8% to 66.3% depending on the availability of homologues. The impact of the different strategies for scanning the database on the prediction was evaluated and is discussed. Our results highlight the usefulness of the method in the context of proteins without any known structural homologues. A scoring function that gives a good estimate of the accuracy of prediction was further developed. This score estimates very well the accuracy of the algorithm (R2 of 0.82). An online version of the tool is provided freely for non-commercial usage at http://www.bo-protscience.fr/kpred/.},
keywords = {team 1, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Sanejouand2017b,
title = {Mutational dynamics of influenza A viruses: a principal component analysis of hemagglutinin sequences of subtype H1},
author = {Yves-Henri Sanejouand},
url = {http://arxiv.org/abs/1710.01594},
year  = {2017},
date = {2017-10-01},
abstract = {A principal component analysis of a multiple sequence alignement of hemagglutinin sequences of subtype H1 has been performed, the sequences being encoded using the amino-acid property that maximizes the weight of the major component. In the case of this alignment, it happens to be a well-known hydrophobicity scale. Interestingly, sequences coming from human have large positive amplitudes along the major component before 2009, and large negative ones afterwards. This means that the 2009 pandemic was associated to a major change in the hydrophobicity pattern of hemagglutinin. The present analysis also highlights the high variability of viral sequences coming from swine. At a more general level, the method proposed in this paper allows to describe a sequence coming from an alignment with a set of numbers, the original point being that the choice of the corresponding property is driven by the data. This approach should allow the application of numerous methods to the study of large multiple sequence alignments.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{pmid28536438,
title = {Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes},
author = {Perrine Paul-Gilloteaux and Vincent Potiron and Grégory Delpon and Stéphane Supiot and Sophie Chiavassa and François Paris and Sylvain V Costes},
doi = {10.1038/s41598-017-01757-6},
issn = {2045-2322},
year  = {2017},
date = {2017-05-23},
urldate = {2017-01-01},
journal = {Sci Rep},
volume = {7},
number = {1},
pages = {2280},
abstract = {The concept of hypofractionation is gaining momentum in radiation oncology centres, enabled by recent advances in radiotherapy apparatus. The gain of efficacy of this innovative treatment must be defined. We present a computer model based on translational murine data for in silico testing and optimization of various radiotherapy protocols with respect to tumour resistance and the microenvironment heterogeneity. This model combines automata approaches with image processing algorithms to simulate the cellular response of tumours exposed to ionizing radiation, modelling the alteration of oxygen permeabilization in blood vessels against repeated doses, and introducing mitotic catastrophe (as opposed to arbitrary delayed cell-death) as a means of modelling radiation-induced cell death. Published data describing cell death in vitro as well as tumour oxygenation in vivo are used to inform parameters. Our model is validated by comparing simulations to in vivo data obtained from the radiation treatment of mice transplanted with human prostate tumours. We then predict the efficacy of untested hypofractionation protocols, hypothesizing that tumour control can be optimized by adjusting daily radiation dosage as a function of the degree of hypoxia in the tumour environment. Further biological refinement of this tool will permit the rapid development of more sophisticated strategies for radiotherapy.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid29218299,
title = {Editorial: Controversies and Perspectives in the Use of Postoperative Radiotherapy for Prostate Cancer},
author = {Alan Dal Pra and Thomas Zilli and Stephane Supiot},
doi = {10.3389/fonc.2017.00275},
issn = {2234-943X},
year  = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
journal = {Front Oncol},
volume = {7},
pages = {275},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{BELKACEMI2017E213,
title = {Patterns of Daily Practice of Hormone Therapy in Unfavorable and Favorable Intermediate-Risk Prostate Cancer: Results of the French PROACT Survey},
author = {Y Belkacemi and I Latorzef and A Hasbini and D Pasquier and A Toledano and C Hennequin and A Bossi and O Chapet and G Crehange and S Guerif and T Duberge and N Allouache and P Clavere and E Gross and S Supiot and D Azria and M Bolla and P Sargos},
url = {https://www.sciencedirect.com/science/article/pii/S0360301617321673},
doi = {https://doi.org/10.1016/j.ijrobp.2017.06.1113},
issn = {0360-3016},
year  = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
journal = {International Journal of Radiation Oncology*Biology*Physics},
volume = {99},
number = {2, Supplement},
pages = {E213},
note = {Proceedings of the American Society for Radiation Oncology},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid28337425,
title = {Post-Prostatectomy Image-Guided Radiotherapy: The Invisible Target Concept},
author = {Florent Vilotte and Mickael Antoine and Maxime Bobin and Igor Latorzeff and Stéphane Supiot and Pierre Richaud and Laurence Thomas and Nicolas Leduc and Stephane Guérif and Jone Iriondo-Alberdi and Renaud de Crevoisier and Paul Sargos},
doi = {10.3389/fonc.2017.00034},
issn = {2234-943X},
year  = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
journal = {Front Oncol},
volume = {7},
pages = {34},
abstract = {In the era of intensity-modulated radiation therapy, image-guided radiotherapy (IGRT) appears crucial to control dose delivery and to promote dose escalation while allowing healthy tissue sparing. The place of IGRT following radical prostatectomy is poorly described in the literature. This review aims to highlight some key points on the different IGRT techniques applicable to prostatic bed radiotherapy. Furthermore, methods used to evaluate target motion and to reduce planning target volume margins will also be explored.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid28620579,
title = {Delineation of the Prostate Bed: The “Invisible Target“ Is Still an Issue?},
author = {Igor Latorzeff and Paul Sargos and Geneviève Loos and Stéphane Supiot and Stéphane Guerif and Christian Carrie},
doi = {10.3389/fonc.2017.00108},
issn = {2234-943X},
year  = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
journal = {Front Oncol},
volume = {7},
pages = {108},
abstract = {For pathological high-risk prostate cancer, adjuvant irradiation has shown a survival benefit. Phase III studies have highlighted that half men would face biochemical relapse and would be candidate for radiotherapy at adjuvant or salvage times. Despite at least four published international contouring guidelines from different collaborative groups, discrepancies remain for volumes, delineation, and margins to be considered in order to optimize radiotherapy planning. This article from "Groupe d'Etude des Tumeurs UroGénitales (GETUG)" members will focus on controversies to help clinicians to create best volume delineation for adjuvant or salvage post prostatectomy radiotherapy.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{avrEQ5:TIRICHINE:2017,
title = {Recent progress in diatom genomics and epigenomics},
author = {Leila Tirichine and Achal Rastogi and Chris Bowler},
url = {http://www.sciencedirect.com/science/article/pii/S1369526616301327},
doi = {10.1016/j.pbi.2017.02.001},
issn = {1369-5266},
year  = {2017},
date = {2017-01-01},
journal = {Current Opinion in Plant Biology},
volume = {36},
pages = {46 - 55},
abstract = {Diatoms are one of the most diverse and successful groups of phytoplankton at the base of the food chain, sustaining life in the ocean and performing vital biogeochemical functions. The last fifteen years have witnessed the comprehensive analysis of several diatom genomes, revealing that they bear traces of their endosymbiotic origins from algal and heterotrophic ancestors, as well as significant gene transfer from bacteria. Their chimeric genomes are further regulated by a range of chromatin-based processes that are characteristic of both plant and animal genomes. We discuss the conservation of gene regulatory mechanisms in diatoms and propose that epigenetic processes may have a significant role in mediating responses to a highly dynamic and unpredictable environment in these organisms.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1021/acs.bioconjchem.7b00374,
title = {Nanofitin as a New Molecular-Imaging Agent for the Diagnosis of Epidermal Growth Factor Receptor Over-Expressing Tumors},
author = {Marine Goux and Guillaume Becker and Harmony Gorré and Sylvestre Dammicco and Ariane Desselle and Dominique Egrise and Natacha Leroi and François Lallemand and Mohamed Ali Bahri and Gilles Doumont and Alain Plenevaux and Mathieu Cinier and André Luxen},
url = {https://doi.org/10.1021/acs.bioconjchem.7b00374},
doi = {10.1021/acs.bioconjchem.7b00374},
year  = {2017},
date = {2017-01-01},
journal = {Bioconjugate Chemistry},
volume = {28},
number = {9},
pages = {2361-2371},
abstract = {Epidermal growth-factor receptor (EGFR) is involved in cell growth and proliferation and is over-expressed in malignant tissues. Although anti-EGFR-based immunotherapy became a standard of care for patients with EGFR-positive tumors, this strategy of addressing cancer tumors by targeting EGFR with monoclonal antibodies is less-developed for patient diagnostic and monitoring. Indeed, antibodies exhibit a slow blood clearance, which is detrimental for positron emission tomography (PET) imaging. New molecular probes are proposed to overcome such limitations for patient monitoring, making use of low-molecular-weight protein scaffolds as alternatives to antibodies, such as Nanofitins with better pharmacokinetic profiles. Anti-EGFR Nanofitin B10 was reformatted by genetic engineering to exhibit a unique cysteine moiety at its C-terminus, which allows the development of a fast and site-specific radiolabeling procedure with 18F–4-fluorobenzamido-N-ethylamino-maleimide (18F–FBEM). The in vivo tumor targeting and imaging profile of the anti-EGFR Cys–B10 Nanofitin was investigated in a double-tumor xenograft model by static small-animal PET at 2 h after tail-vein injection of the radiolabeled Nanofitin 18F–FBEM–Cys–B10. The image showed that the EGFR-positive tumor (A431) is clearly delineated in comparison to the EGFR-negative tumor (H520) with a significant tumor-to-background contrast. 18F–FBEM–Cys–B10 demonstrated a significantly higher retention in A431 tumors than in H520 tumors at 2.5 h post-injection with a A431-to-H520 uptake ratio of 2.53 ± 0.18 and a tumor-to-blood ratio of 4.55 ± 0.63. This study provides the first report of Nanofitin scaffold used as a targeted PET radiotracer for in vivo imaging of EGFR-positive tumor, with the anti-EGFR B10 Nanofitin used as proof-of-concept. The fast generation of specific Nanofitins via a fully in vitro selection process, together with the excellent imaging features of the Nanofitin scaffold, could facilitate the development of valuable PET-based companion diagnostics.},
note = {PMID: 28825794},
keywords = {out_lab, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{DAMMICCO201733,
title = {Regiospecific radiolabelling of Nanofitin on Ni magnetic beads with [18F]FBEM and in vivo PET studies},
author = {Sylvestre Dammicco and Marine Goux and Christian Lemaire and Guillaume Becker and Mohamed Ali Bahri and Alain Plenevaux and Mathieu Cinier and André Luxen},
url = {https://www.sciencedirect.com/science/article/pii/S0969805116303304},
doi = {https://doi.org/10.1016/j.nucmedbio.2017.04.006},
issn = {0969-8051},
year  = {2017},
date = {2017-01-01},
journal = {Nuclear Medicine and Biology},
volume = {51},
pages = {33-39},
abstract = {Introduction 
Nanofitins are low molecular weight, single chain and cysteine-free protein scaffolds able to selectively bind a defined biological target. They derive from Sac7d bacterial protein family and are highly stable over a wide range of pH (0–13) and temperature (Tm ~80°C). Their extreme stability, low cost of production and high tolerability for chemical coupling make Nanofitins a very interesting alternative to antibodies and their fragments. Here, a hexahistidine tagged model Nanofitin (H4) directed against hen egg white lysozyme was radiolabelled and injected in mice to provide a baseline biodistribution and pharmacokinetic profiles to support future Nanofitin development programs. 
Method 
A single cysteine residue has been genetically inserted in a model Nanofitin and its regioselective radiolabelling has been performed with 4-[18F]fluorobenzamido-N-ethylamino-maleimide ([18F]FBEM). The synthesis of [18F]FBEM has been completely implemented on a radiosynthesis unit (FastLab) including HPLC purification and formulation. Coupling with the [18F]FBEM has been achieved on a solid support (Ni magnetic beads) allowing rapid purification at room temperature without organic solvent. PET-MRI studies on C57BL/6 mice were conducted after injection of [18F]FBEM-Cys-H4 in order to access the biodistribution of this Nanofitin model. 
Results Radiochemical yield (decay corrected) of 54±7% (n=4) was obtained after optimization for coupling the [18F]FBEM to Nanofitin. Pharmacokinetics results of [18F]FBEM-Cys-H4 revealed a fast clearance through the liver and the kidneys. 
Conclusion 
An efficient new method on Ni magnetic beads was developed to radiolabelled his-tagged biomolecules with [18F]FBEM. This procedure was applied on a Nanofitin model Cys-H4 and biodistribution kinetic studies were achieved to evaluate the potential use of Nanofitin for diagnostic imaging. Fast clearance indicates that Nanofitins represent very interesting tools for diagnostic imaging. Image 1},
keywords = {[F]FBEM, Biodistribution, Nanofitin, Ni beads, out_lab, PET, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{hong2017cat,
title = {Cat-D: a targeted sequencing method for the simultaneous detection of small DNA mutations and large DNA deletions with flexible boundaries},
author = {Ru Hong and Udita Chandola and Li-Feng Zhang},
doi = {10.1038/s41598-017-15764-0},
year  = {2017},
date = {2017-01-01},
journal = {Scientific reports},
volume = {7},
number = {1},
pages = {1--8},
publisher = {Nature Publishing Group},
abstract = {We developed a targeted DNA sequencing method that is capable of detecting a comprehensive panel of DNA mutations including small DNA mutations and large DNA deletions with unknown/flexible boundaries. The method directly identifies the large DNA deletions (Cat-D) without relying on sequencing coverage to make the genotype calls. We performed the method to simultaneously detect 10 small DNA mutations in β-thalassemia and 2 large genomic deletions in α-thalassemia from 10 genomic DNA samples. Cat-D was performed on 8 genomic DNA samples in duplicate. The 18 Cat-D samples were combined in one sequencing run. In total, 216 genotype calls were made, and 215 of the genotype calls were accurate. No false negative genotype calls were made. One false positive genotype call was made on one target mutation in one experimental duplicate from a genomic DNA sample. In summary, Cat-D can be developed into a robust, high-throughput and cost-effective method suitable for population-based carrier screens.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{bastard2017parallel,
title = {Parallel evolution of non-homologous isofunctional enzymes in methionine biosynthesis},
author = {Karine Bastard and Alain Perret and Aline Mariage and Thomas Bessonnet and Agnès Pinet-Turpault and Jean-Louis Petit and Ekaterina Darii and Pascal Bazire and Carine Vergne-Vaxelaire and Clémence Brewee and Adrien Debard and Virginie Pellouin and Marielle Besnard-Gonnet and François Artiguenave and Claudine Médigue and David Vallenet and Antoine Danchin and Anne Zaparucha and Jean Weissenbach and Marcel Salanoubat and Véronique de Berardinis },
doi = {10.1038/nchembio.2397},
year  = {2017},
date = {2017-01-01},
journal = {Nature Chemical Biology},
volume = {13},
number = {8},
pages = {858},
publisher = {Nature Publishing Group},
abstract = {Experimental validation of enzyme function is crucial for genome interpretation, but it remains challenging because it cannot be scaled up to accommodate the constant accumulation of genome sequences. We tackled this issue for the MetA and MetX enzyme families, phylogenetically unrelated families of acyl-L-homoserine transferases involved in L-methionine biosynthesis. Members of these families are prone to incorrect annotation because MetX and MetA enzymes are assumed to always use acetyl-CoA and succinyl-CoA, respectively. We determined the enzymatic activities of 100 enzymes from diverse species, and interpreted the results by structural classification of active sites based on protein structure modeling. We predict that &gt;60% of the 10,000 sequences from these families currently present in databases are incorrectly annotated, and suggest that acetyl-CoA was originally the sole substrate of these isofunctional enzymes, which evolved to use exclusively succinyl-CoA in the most recent bacteria. We also uncovered a divergent subgroup of MetX enzymes in fungi that participate only in L-cysteine biosynthesis as O-succinyl-L-serine transferases.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Ejlassi2017b,
title = {Histones H3 and H4 require their relevant amino-tails for efficient nuclear import and replication-coupled chromatin assembly in vivo},
author = {Aïda Ejlassi and Vanessa Menil-Philippot and Angélique Galvani and Christophe Thiriet},
doi = {10.1038/s41598-017-03218-6},
issn = {20452322},
year  = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
journal = {Scientific Reports},
volume = {7},
number = {1},
pages = {1--10},
abstract = {Concomitant chromatin assembly and DNA duplication is essential for cell survival and genome integrity, and requires newly synthesized histones. Although the N-terminal domains of newly synthesized H3 and H4 present critical functions, their requirement for replication-coupled chromatin assembly is controversial. Using the unique capability of the spontaneous internalization of exogenous proteins in Physarum, we showed that H3 and H4 N-tails present critical functions in nuclear import during the S-phase, but are dispensable for assembly into nucleosomes. However, our data revealed that chromatin assembly in the S-phase of complexes presenting ectopic N-terminal domains occurs by a replication-independent mechanism. We found that replication-dependent chromatin assembly requires an H3/H4 complex with the relevant N-tail domains, suggesting a concomitant recognition of the two histone domains by histone chaperones.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
@article{Menil-Philippot2017,
title = {Physarum polycephalum for Studying the Function of Histone Modifications In Vivo.},
author = {Vanessa Menil-Philippot and Christophe Thiriet},
doi = {10.1007/978-1-4939-6630-1_15},
issn = {1940-6029 (Electronic)},
year  = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {1528},
pages = {245--256},
abstract = {Histone modifications have been widely correlated with genetic activities. However, how these posttranslational modifications affect the dynamics and the structure of chromatin is poorly understood. Here, we describe the incorporation of the exogenous histone proteins into the slime mold Physarum polycephalum, which has been revealed to be a valuable tool for examining different facets of the function histones in chromatin dynamics like replication-coupled chromatin assembly, histone exchange, and nucleosome turnover.},
keywords = {Chromatin, Chromatin Assembly and Disassembly, DNA Replication, genetics, Histone Code, histones, metabolism, Nucleosomes, Physarum polycephalum, physiology, Post-Translational, Protein Processing},
pubstate = {published},
tppubtype = {article}
}
@article{Rouaud2017,
title = {Complement C3 of the innate immune system secreted by muscle adipogenic cells promotes myogenic differentiation},
author = {Thierry Rouaud and Nader Siami and Tanaelle Dupas and Pascal Gervier and Marie France Gardahaut and Gwenola Auda-Boucher and Christophe Thiriet},
doi = {10.1038/s41598-017-00099-7},
issn = {20452322},
year  = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
journal = {Scientific Reports},
volume = {7},
number = {1},
pages = {1--9},
abstract = {Myogenic differentiation results in different cell type cooperation, but the molecules involved in the myogenic cell activation remain elusive. Here, we show that muscle-resident pre-adipocytes promote myogenic differentiation through the secretion of factors. Using proteomic and transcriptomic analyses, we identified that proliferative adipogenic lineage cells produce and secrete a key factor of the innate immune system, the complement C3. Cell culture experiments revealed that C3 promotes the differentiation of myogenic progenitors following internalisation of the immune molecule. These data demonstrate that the third component of the complement system, which is a pivotal factor in the immune response to pathogens, is also involved in the differentiation of myogenic progenitor cells.},
keywords = {thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Bosseboeuf2017,
title = {Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens},
author = {Adrien Bosseboeuf and Delphine Feron and Anne Tallet and Cédric Rossi and Cathy Charlier and Laurent Garderet and Denis Caillot and Philippe Moreau and Marina Cardó-Vila and Renata Pasqualini and Wadih Arap and Alfreda Destea Nelson and Bridget S Wilson and Hélène Perreault and Eric Piver and Pierre Weigel and François Girodon and Jean Harb and Edith Bigot-Corbel and Sylvie Hermouet},
doi = {10.1172/jci.insight.95367},
issn = {0021-9738},
year  = {2017},
date = {2017-01-01},
journal = {JCI Insight},
volume = {2},
number = {19},
pages = {1--18},
abstract = {Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens. Antigen specificity of purified mc IgG from a large patient cohort (n = 244) was determined using a multiplex infectious-antigen array (MIAA), which screens for reactivity to purified antigens or lysates from 9 pathogens. Purified mc IgG from 23.4% of patients (57 of 244) specifically recognized 1 pathogen in the MIAA. EBV was the most frequent target (15.6%), with 36 of 38 mc IgGs recognizing EBV nuclear antigen-1 (EBNA-1). MM patients with EBNA-1-specific mc IgG (14.0%) showed substantially greater bone marrow plasma cell infiltration and higher β2-microglobulin and inflammation/infection-linked cytokine levels compared with other smoldering myeloma/MM patients. Five other pathogens were the targets of mc IgG: herpes virus simplex-1 (2.9%), varicella zoster virus (1.6%), cytomegalovirus (0.8%), hepatitis C virus (1.2%), and H. pylori (1.2%). We conclude that a dysregulated immune response to infection may underlie disease onset and/or progression of MGUS and MM for subsets of patients.},
keywords = {impact, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Laniau2017,
title = {Combining graph and flux-based structures to decipher phenotypic essential metabolites within metabolic networks},
author = {J Laniau and C Frioux and J Nicolas and C Baroukh and M-P Cortes and J Got and Camille Trottier and D Eveillard and A Siegel},
doi = {10.7717/peerj.3860},
issn = {21678359},
year  = {2017},
date = {2017-01-01},
journal = {PeerJ},
volume = {2017},
number = {10},
abstract = {Background. The emergence of functions in biological systems is a long-standing issue that can now be addressed at the cell level with the emergence of high throughput technologies for genome sequencing and phenotyping. The reconstruction of complete metabolic networks for various organisms is a key outcome of the analysis of these data, giving access to a global view of cell functioning. The analysis of metabolic networks may be carried out by simply considering the architecture of the reaction network or by taking into account the stoichiometry of reactions. In both approaches, this analysis is generally centered on the outcome of the network and considers all metabolic compounds to be equivalent in this respect. As in the case of genes and reactions, about which the concept of essentiality has been developed, it seems, however, that some metabolites play crucial roles in system responses, due to the cell structure or the internal wiring of the metabolic network. Results. We propose a classification of metabolic compounds according to their capacity to influence the activation of targeted functions (generally the growth phenotype) in a cell. We generalize the concept of essentiality to metabolites and introduce the concept of the phenotypic essential metabolite (PEM) which influences the growth phenotype according to sustainability, producibility or optimal-efficiency criteria. We have developed and made available a tool, Conquests, which implements a method combining graph-based and flux-based analysis, two approaches that are usually considered separately. The identification of PEMs is made effective by using a logical programming approach. Conclusion. The exhaustive study of phenotypic essential metabolites in six genomescale metabolic models suggests that the combination and the comparison of graph, stoichiometry and optimal flux-based criteria allows some features of the metabolic network functionality to be deciphered by focusing on a small number of compounds.},
keywords = {Answer Set Programming, Constraint-based analysis, Essential metabolite, Graph-based analysis, Metabolic networks, out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Yaremenko2017,
title = {Cyclic peroxides as promising anticancer agents: in vitro cytotoxicity study of synthetic ozonides and tetraoxanes on human prostate cancer cell lines},
author = {Ivan A Yaremenko and Mikhail A Syroeshkin and Dmitri O Levitsky and Fabrice Fleury and Alexander O Terent'ev},
url = {https://doi.org/10.1007/s00044-016-1736-2},
doi = {10.1007/s00044-016-1736-2},
issn = {1554-8120},
year  = {2017},
date = {2017-01-01},
journal = {Medicinal Chemistry Research},
volume = {26},
number = {1},
pages = {170--179},
abstract = {Synthetic ozonides and tetraoxanes were shown to have high cytotoxicity in vitro when tested on androgen-independent prostate cancer cell lines DU145 and PC3, which is in some cases was higher than that of doxorubicin, cisplatin, etoposide, artemisinin, and artesunate. Activity of ozonide stereoisomers differs from each other. This difference in activity and absence of correlation between activity of stereoisomers and their oxidative properties allow us to suggest existence of a quite specific mechanism of cytotoxicity of these endoperoxides different from a traditional mechanism based mainly on oxidative properties of peroxides.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Levitsky2017,
title = {ANABOLIC CYANOSTEROIDS AND THEIR BIOLOGICAL ACTIVITIES – A BRIEF REVIEW},
author = {Dmitri O Levitsky and Tatyana A Gloriozova and Vladimir V Poroikov and M Valery},
doi = {10.20959/wjpps201712-10618},
isbn = {2017121061},
year  = {2017},
date = {2017-01-01},
volume = {6},
number = {12},
pages = {127--151},
abstract = {The present review describes the biological activities of synthetic anabolic cyanosteroids. More than forty biologically active compounds have shown confirmed anti-tumour, anti-inflammatory, antiviral and other activities. The structures and reported and predicted activities of synthetic cyanosteroids are available. With the computer programme PASS and based on structure–activity relationships (SAR), some additional activities are also predicted, which point towards new possible applications of these lipids. This review emphasizes the role of cyanosteroids as an important source and potential leads for drug discovery and they are of great interest to chemists, physicians, biologists, pharmacologists and the pharmaceutical industry. KEYWORDS:},
keywords = {activities, anabolic, Cyanosteroids, lipids, PASS., SAR, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Faucon2017,
title = {Bioconjugated fluorescent organic nanoparticles targeting EGFR-overexpressing cancer cells},
author = {Adrien Faucon and Houda Benhelli-Mokrani and Fabrice Fleury and Stéphanie Dutertre and Marc Tramier and Joanna Boucard and Lénaïc Lartigue and Steven Nedellec and Philippe Hulin and Eléna Ishow},
doi = {10.1039/c7nr06533g},
issn = {20403372},
year  = {2017},
date = {2017-01-01},
journal = {Nanoscale},
volume = {9},
number = {45},
pages = {18094--18106},
publisher = {Royal Society of Chemistry},
abstract = {The field of optical bioimaging has considerably flourished with the advent of sophisticated microscopy techniques and ultra-bright fluorescent tools. Fluorescent organic nanoparticles (FONs) have thus recently appeared as very attractive labels for their high payload, absence of cytotoxicity and eventual biodegradation. Nevertheless, their bioconjugation to target specific receptors with high imaging contrast is scarcely performed. Moreover, assessing the reality of bioconjugation represents high challenges given the sub-nanomolar concentrations resulting from the commonly adopted nanoprecipitation fabrication process. Here, we describe how the combination of a magnetic shell allows us to easily generate red-emitting FONs conjugated with the epidermal growth factor ligand (EGF), a small protein promoting cancer cell proliferation by activating the EGF receptor (EGFR) pathway. Dual color fluorescence correlation spectroscopy combined with immunofluorescence is originally harnessed in its time trace mode to unambiguously demonstrate covalent attachment between the FON and EGF at sub-nanomolar concentrations. Strong asymmetric clustering of EGF-conjugated FONs is observed at the membrane of MDA-MB-468 human breast cancer cells overexpressing EGF receptors using super-resolution fluorescence microscopy. Such high recruitment of EGF-conjugated FONs is attributed to their EGF multivalency (4.7 EGF per FON) which enables efficient EGFR activation and subsequent phosphorylation. The large hydrodynamic diameter (DH ∼ 301 nm) of EGF-conjugated FONs prevents immediate engulfment of the sequestered receptors, which provides very bright and localized spots in less than 30 minutes. The reported bioconjugated nanoassemblies could thus serve as ultra-bright probes of breast cancer cells with EGFR-overexpression that is often associated with poor prognosis.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Alligand2017,
title = {Functional effects of diphosphomimetic mutations at cAbl-mediated phosphorylation sites on Rad51 recombinase activity},
author = {Brendan Alligand and Magali {Le Breton} and Damien Marquis and François Vallette and Fabrice Fleury},
url = {http://dx.doi.org/10.1016/j.biochi.2017.05.020},
doi = {10.1016/j.biochi.2017.05.020},
issn = {61831638},
year  = {2017},
date = {2017-01-01},
journal = {Biochimie},
volume = {139},
pages = {115--124},
publisher = {Elsevier Ltd},
abstract = {Homologous Recombination enables faithful repair of the deleterious double strand breaks of DNA. This pathway relies on Rad51 to catalyze homologous DNA strand exchange. Rad51 is known to be phosphorylated in a sequential manner on Y315 and then on Y54, but the effect of such phosphorylation on Rad51 function remains poorly understood. We have developed a phosphomimetic model in order to study all the phosphorylation states. With the purified phosphomimetic proteins we performed in vitro assays to determine the activity of Rad51. Here we demonstrate the inhibitory effect of the double phosphomimetic mutant and suggest that it may be due to a defect in nucleofilament formation.},
keywords = {DNA repair, Homologous Recombination, Phosphomimetic, Protein phosphorylation, Rad51, team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@phdthesis{david2017conception,
title = {Conception rationnelle dénzyme: conversion de glycoside hydrolases en transglycosidases},
author = {Benoît David},
url = {https://www.theses.fr/2017NANT1044},
year  = {2017},
date = {2017-01-01},
school = {Université de Nantes},
abstract = {Catalyseurs de la dégradation de polysaccharides dans le cadre de diverses applications industrielles, de nombreuses glycoside hydrolases (GH) possèdent également une activité de transglycosylation qui peut être exploitée pour la synthèse dóligosaccharides. Afin dáugmenter cette activité, minoritaire par rapport à l'hydrolyse, des expériences de mutagenèse rationnelle peuvent être employées. Toutefois, lénsemble des bases moléculaires régissant l’équilibre entre ces deux activités reste en revanche difficile a élucider. L'étude de quatre GH (Ttβgly, AgaD, TcTS, TrSA) par simulation de dynamique moléculaire a permis la découverte de canaux déau internes à leurs structures et connectant le site actif au milieu. Cette observation suggère que les canaux déau internes aux GH pourraient être impliqués dans leur activité d'hydrolyse. Plusieurs paires de résidus bordant deux de ces canaux ont été mis en évidence chez Ttβgly et AgaD et semblent contrôler le passage de léau du canal vers le site actif. La mutagenèse de ces résidus a été entreprise afin de tenter dáugmenter láctivité de transglycosylation chez ces deux enzymes. Une réduction de l'hydrolyse d'un facteur 7 et 50 au profit de láctivité de transglycosylation a été caractérisée chez les deux meilleurs mutants de Ttβgly et AgaD, respectivement. Lánalyse des simulations a révélé que ces résultats étaient corrélés à une augmentation de la dynamique des molécules déau internes aux deux canaux étudiés. Cette étude souligne ainsi límportance fonctionnelle de léau interne aux hydrolases et suggère que língénierie de sa dynamique peut constituer une approche originale pour convertir les GH en transglycosidases.},
keywords = {team 1, team 2, thesis},
pubstate = {published},
tppubtype = {phdthesis}
}
@article{Dion2017c,
title = {Lactosamine-Based Derivatives as Tools to Delineate the Biological Functions of Galectins: Application to Skin Tissue Repair},
author = {Johann Dion and Frédérique Deshayes and Nataliya Storozhylova and Tamara Advedissian and Annie Lambert and Mireille Viguier and Charles Tellier and Christophe Dussouy and Françoise Poirier and Cyrille Grandjean},
doi = {10.1002/cbic.201600673},
issn = {14397633},
year  = {2017},
date = {2017-01-01},
journal = {ChemBioChem},
volume = {18},
number = {8},
pages = {782--789},
abstract = {Galectins have been recognized as potential novel therapeutic targets for the numerous fundamental biological processes in which they are involved. Galectins are key players in homeostasis, and as such their expression and function are finely tuned in vivo. Thus, their modes of action are complex and remain largely unexplored, partly because of the lack of dedicated tools. We thus designed galectin inhibitors from a lactosamine core, functionalized at key C2 and C3′ positions by aromatic substituents to ensure both high affinity and selectivity, and equipped with a spacer that can be modified on demand to further modulate their physico-chemical properties. As a proof-of-concept, galectin-3 was selectively targeted. The efficacy of the synthesized di-aromatic lactosamine tools was shown in cellular assays to modulate collective epithelial cell migration and to interfere with actin/cortactin localization.},
keywords = {cell migration, drug design, galectin-3, inhibitors, skin tissue repair, team 2, thesis, wound healing},
pubstate = {published},
tppubtype = {article}
}
@article{Coppin2017,
title = {Galectin-3 is a non-classic RNA binding protein that stabilizes the mucin MUC4 mRNA in the cytoplasm of cancer cells},
author = {Lucie Coppin and Audrey Vincent and Frédéric Frénois and Belinda Duch{ê}ne and Fatima Lahdaoui and Laurence Stechly and Florence Renaud and Céline Villenet and Isabelle Van Seuningen and Emmanuelle Leteurtre and Johann Dion and Cyrille Grandjean and Fran{ç}oise Poirier and Martin Figeac and Delphine Delacour and Nicole Porchet and Pascal Pigny},
doi = {10.1038/srep43927},
issn = {20452322},
year  = {2017},
date = {2017-01-01},
journal = {Scientific Reports},
volume = {7},
number = {March},
pages = {1--14},
abstract = {Pancreatic cancer cells express high levels of MUC1, MUC4 and MUC16 mRNAs that encode membrane-bound mucins. These mRNAs share unusual features such as a long half-life. However, it remains unknown how mucin mRNA stability is regulated. Galectin-3 (Gal-3) is an endogenous lectin playing important biological functions in epithelial cells. Gal-3 is encoded by LGALS3 which is up-regulated in pancreatic cancer. Despite the absence of a RNA-recognition motif, Gal-3 interacts indirectly with pre-mRNAs in the nucleus and promotes constitutive splicing. However a broader role of Gal-3 in mRNA fate is unexplored. We report herein that Gal-3 increases MUC4 mRNA stability through an intermediate, hnRNP-L which binds to a conserved CA repeat element in the 3′UTR in a Gal-3 dependent manner and also controls Muc4 mRNA levels in epithelial tissues of Gal3-/- mice. Gal-3 interacts with hnRNP-L in the cytoplasm, especially during cell mitosis, but only partly associates with protein markers of P-Bodies or Stress Granules. By RNA-IP plus RNA-seq analysis and imaging, we demonstrate that Gal-3 binds to mature spliced MUC4 mRNA in the perinuclear region, probably in hnRNP-L-containing RNA granules. Our findings highlight a new role for Gal-3 as a non-classic RNA-binding protein that regulates MUC4 mRNA post-transcriptionally.},
keywords = {team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Alvarez-Dorta2017,
title = {Magnetic Nanoparticles Coated with Thiomannosides or Iminosugars to Switch and Recycle Galactosidase Activity},
author = {Dimitri Alvarez-Dorta and Yoan Brissonnet and Amélie Saumonneau and David Deniaud and Julien Bernard and Xibo Yan and Charles Tellier and Franck Daligault and Sébastien G Gouin},
doi = {10.1002/slct.201702063},
issn = {23656549},
year  = {2017},
date = {2017-01-01},
journal = {ChemistrySelect},
volume = {2},
number = {29},
pages = {9552--9556},
abstract = {Glycosidase effectors have rarely been reported despite their great potential interest in pharmaceutical sciences and industry. Magnetic nanoparticles were coated with thiomannosides (SMan@Fe3O4) or the broad spectrum glycosidase inhibitor deoxynojirimycin (DNJ@Fe3O4). The coated ligands were shown to exert a fully reverse effect on a model galactosidase (AgaB), with SMan@Fe3O4 or DNJ@Fe3O4 ligands acting as an enzyme inhibitor (Ki=3.7 µM) or a strong activator (250% higher AgaB velocity at 50 µM), respectively. This is striking considering that monovalent soluble SMan and DNJ analogues do not interact with AgaB at millimolar concentrations. The AgaB-DNJ@Fe3O4 enzyme-effector complex could be magnetically recycled and still showed a higher activity compared to free AgaB after four catalytic cycles. The “boost and recycle” procedure may provide interesting perspectives in glycosidase biocatalysis.},
keywords = {d-zyme, Enzymatic effectors, Glycosidases, Iminosugars, Magnetic nanoparticles, Multivalency, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{Legentil2017,
title = {Regioselective Galactofuranosylation for the Synthesis of Disaccharide Patterns Found in Pathogenic Microorganisms},
author = {Laurent Legentil and Yari Cabezas and Olivier Tasseau and Charles Tellier and Franck Daligault and Vincent Ferri{è}res},
doi = {10.1021/acs.joc.7b00565},
issn = {15206904},
year  = {2017},
date = {2017-01-01},
journal = {Journal of Organic Chemistry},
volume = {82},
number = {14},
pages = {7114--7122},
abstract = {Koenigs-Knorr glycosylation of acceptors with more than one free hydroxyl group by 2,3,5,6-tetrabenzoyl galactofuranosyl bromide was performed using diphenylborinic acid 2-aminoethyl ester (DPBA) as inducer of regioselectivity. High regioselectivity for the glycosylation on the equatorial hydroxyl group of the acceptor was obtained thanks to the transient formation of a borinate adduct of the corresponding 1,2-cis diol. Nevertheless formation of orthoester byproducts hampered the efficiency of the method. Interestingly electron-withdrawing groups on O-6 or on C-1 of the acceptor displaced the reaction in favor of the desired galactofuranosyl containing disaccharide. The best yield was obtained for the furanosylation of p-nitrophenyl 6-O-acetyl mannopyranoside. Precursors of other disaccharides, found in the glycocalix of some pathogens, were synthesized according to the same protocol with yields ranging from 45 to 86%. This is a good alternative for the synthesis of biologically relevant glycoconjugates.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{RN11,
title = {Haustorium initiation in the obligate parasitic plant Phelipanche ramosa involves a host-exudated cytokinin signal},
author = {Vincent Goyet and Estelle Billard and Jean-Bernard Pouvreau and Marc-Marie Lechat and Sandra Pelletier and Muriel Bahut and Fabrice Monteau and Lukas Spíchal and Philippe Delavault and Grégory Montiel and Philippe Simier},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853424/pdf/erx359.pdf},
doi = {10.1093/jxb/erx359},
issn = {0022-0957 (Print) 0022-0957},
year  = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
journal = {J Exp Bot},
volume = {68},
number = {20},
pages = {5539-5552},
abstract = {The heterotrophic lifestyle of parasitic plants relies on the development of the haustorium, a specific infectious organ required for attachment to host roots. While haustorium development is initiated upon chemodetection of host-derived molecules in hemiparasitic plants, the induction of haustorium formation remains largely unknown in holoparasitic species such as Phelipanche ramosa. This work demonstrates that the root exudates of the host plant Brassica napus contain allelochemicals displaying haustorium-inducing activity on P. ramosa germinating seeds, which increases the parasite aggressiveness. A de novo assembled transcriptome and microarray approach with P. ramosa during early haustorium formation upon treatment with B. napus root exudates allowed the identification of differentially expressed genes involved in hormone signaling. Bioassays using exogenous cytokinins and the specific cytokinin receptor inhibitor PI-55 showed that cytokinins induced haustorium formation and increased parasite aggressiveness. Root exudates triggered the expression of cytokinin-responsive genes during early haustorium development in germinated seeds, and bio-guided UPLC-ESI(+)-/MS/MS analysis showed that these exudates contain a cytokinin with dihydrozeatin characteristics. These results suggest that cytokinins constitutively exudated from host roots play a major role in haustorium formation and aggressiveness in P. ramosa.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{SANEJOUAND201713,
title = {A singular mutation in the hemagglutinin of the 1918 pandemic virus},
author = {Yves-Henri Sanejouand},
url = {http://www.sciencedirect.com/science/article/pii/S0003986117302576},
doi = {https://doi.org/10.1016/j.abb.2017.05.013},
issn = {0003-9861},
year  = {2017},
date = {2017-01-01},
journal = {Archives of Biochemistry and Biophysics},
volume = {625-626},
pages = {13--16},
abstract = {The influenza pandemic of 1918–1919 killed at least 50 million people. The reasons why this pandemic was so deadly remain largely unknown [9]. However, It has been shown that the 1918 viral hemagglutinin allows to reproduce the hallmarks of the illness observed during the original pandemic [11]. Thanks to the wealth of hemagglutinin sequences accumulated over the last decades, amino-acid substitutions that are found in the 1918–1919 sequences but rare otherwise can be identified with high confidence. Noteworthy, Gly 188, which is located within a key motif of the receptor binding site, has never been observed again in sequences of human viruses of subtype H1. Monitoring this singular mutation in viral sequences may help prevent another dramatic pandemic.},
keywords = {Hemagglutinin, Influenza, Mutations, Pandemic, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{Mahajan2017,
title = {Jumping between protein conformers using normal modes},
author = {Swapnil Mahajan and Yves-Henri Sanejouand},
doi = {10.1002/jcc.24803},
issn = {1096987X},
year  = {2017},
date = {2017-01-01},
journal = {Journal of Computational Chemistry},
volume = {38},
number = {18},
pages = {1622--1630},
abstract = {The relationship between the normal modes of a protein and its functional conformational change has been studied for decades. However, using this relationship in a predictive context remains a challenge. In this work, we demonstrate that, starting from a given protein conformer, it is possible to generate in a single step model conformers that are less than 1 Å (Cα-RMSD) from the conformer which is the known endpoint of the conformational change, particularly when the conformational change is collective in nature. Such accurate model conformers can be generated by following either the so-called robust or the 50 lowest-frequency modes obtained with various Elastic Network Models (ENMs). Interestingly, the quality of many of these models compares well with actual crystal structures, as assessed by the ROSETTA scoring function and PROCHECK. The most accurate and best quality conformers obtained in the present study were generated by using the 50 lowest-frequency modes of an all-atom ENM. However, with less than ten robust modes, which are identified without any prior knowledge of the nature of the conformational change, nearly 90% of the motion described by the 50 lowest-frequency modes of a protein can be captured. Such results strongly suggest that exploring the robust modes of ENMs may prove efficient for sampling the functionally relevant conformational repertoire of many proteins. textcopyright 2017 Wiley Periodicals, Inc.},
keywords = {conformational change, elastic network model, low-frequency modes, robust modes, ROSETTA, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{Atmanene2017,
title = {Biophysical and structural characterization of mono/di-arylated lactosamine derivatives interaction with human galectin-3},
author = {Cédric Atmanene and Céline Ronin and Stéphane Téletchéa and François Moana Gautier and Florence Djedaïni-Pilard and Fabrice Ciesielski and Valérie Vivat and Cyrille Grandjean},
doi = {10.1016/j.bbrc.2017.05.150},
issn = {10902104},
year  = {2017},
date = {2017-01-01},
journal = {Biochemical and Biophysical Research Communications},
volume = {489},
number = {3},
pages = {281--286},
abstract = {Combination of biophysical and structural techniques allowed characterizing and uncovering the mechanisms underlying increased binding affinity of lactosamine derivatives for galectin 3. In particular, complementing information gathered from X-ray crystallography, native mass spectrometry and isothermal microcalorimetry showed favorable enthalpic contribution of cation-π interaction between lactosamine aryl substitutions and arginine residues from the carbohydrate recognition domain, which resulted in two log increase in compound binding affinity. This incrementing strategy allowed individual contribution of galectin inhibitor moieties to be dissected. Altogether, our results suggest that core and substituents of these saccharide-based inhibitors can be optimized separately, providing valuable tools to study the role of galectins in diseases.},
keywords = {cation-π, Galectin-3 inhibitor, Isothermal titration calorimetry, Lactosamine, Native mass spectrometry, team 1, X-ray crystallography},
pubstate = {published},
tppubtype = {article}
}
@article{Labbe2017,
title = {The alternatively spliced LRRFIP1 Isoform-1 is a key regulator of the Wnt/β-catenin transcription pathway},
author = {Pauline Labbé and Emilie Faure and Simon Lecointe and Solena {Le Scouarnec} and Florence Kyndt and Marie Marrec and Thierry {Le Tourneau} and Bernard Offmann and Cécile Duplaà and Stéphane Zaffran and Jean Jacques Schott and Jean Merot},
doi = {10.1016/j.bbamcr.2017.03.008},
issn = {18792596},
year  = {2017},
date = {2017-01-01},
journal = {Biochimica et Biophysica Acta - Molecular Cell Research},
volume = {1864},
number = {7},
pages = {1142--1152},
abstract = {The GC-rich Binding Factor 2/Leucine Rich Repeat in the Flightless 1 Interaction Protein 1 gene (GCF2/LRRFIP1) is predicted to be alternatively spliced in five different isoforms. Although important peptide sequence differences are expected to result from this alternative splicing, to date, only the gene transcription regulator properties of LRRFIP1-Iso5 were unveiled. Based on molecular, cellular and biochemical data, we show here that the five isoforms define two molecular entities with different expression profiles in human tissues, subcellular localizations, oligomerization properties and transcription enhancer properties of the canonical Wnt pathway. We demonstrated that LRRFIP1-Iso3, -4 and -5, which share over 80% sequence identity, are primarily located in the cell cytoplasm and form homo and hetero-multimers between each other. In contrast, LRRFIP1-Iso1 and -2 are primarily located in the cell nucleus in part thanks to their shared C-terminal domain. Furthermore, we showed that LRRFIP1-Iso1 is preferentially expressed in the myocardium and skeletal muscle. Using the in vitro Topflash reporter assay we revealed that among LRRFIP1 isoforms, LRRFIP1-Iso1 is the strongest enhancer of the β-catenin Wnt canonical transcription pathway thanks to a specific N-terminal domain harboring two critical tryptophan residues (W76, 82). In addition, we showed that the Wnt enhancer properties of LRRFIP1-Iso1 depend on its homo-dimerisation which is governed by its specific coiled coil domain. Together our study identified LRRFIP1-Iso1 as a critical regulator of the Wnt canonical pathway with a potential role in myocyte differentiation and myogenesis.},
keywords = {Coiled coil domain, LEF-TCF, Leucine rich repeat, Muscle differentiation, team 1, Wnt catenin transcription},
pubstate = {published},
tppubtype = {article}
}
@article{David2017a,
title = {Internal Water Dynamics Control the Transglycosylation/Hydrolysis Balance in the Agarase (AgaD) of Zobellia galactanivorans},
author = {Benoit David and Romain Irague and Diane Jouanneau and Franck Daligault and Mirjam Czjzek and Yves-Henri Sanejouand and Charles Tellier},
doi = {10.1021/acscatal.7b00348},
issn = {21555435},
year  = {2017},
date = {2017-01-01},
journal = {ACS Catalysis},
volume = {7},
number = {5},
pages = {3357--3367},
abstract = {In retaining glycoside hydrolases (GHs), transglycosylase activity is often low due to the natural hydrolytic activity that is favored in water. Improving the relative transglycosylase activity of these enzymes is of particular interest to obtain enzymes suitable for the synthesis of oligosaccharides. We explored the effect of engineering the water dynamics within the endo-β-agarase AgaD on the transglycosylation/hydrolysis (T/H) balance. By mutating three amino acids (D341, Q342, and S351), which could control water access to a putative water channel ending close to the active site, we obtained AgaD variants with an inverted T/H balance. For the best mutant, D341L/Q342H/S351F, the hydrolysis activity was reduced 50-fold in comparison to the wild type, while the transglycosylase activity was maintained and even slightly improved. This variant produced a large amount of oligo-agaroses by a disproportionation reaction with deca-agarose as the substrate. Molecular dynamics simulations showed that these enzymatic modifications were correlated with higher water dynamics, as revealed by a marked reduction in the water survival time and a decrease in the purge time of water in a channel ending close to the active site. These results suggest that modifying the water dynamics in GHs could be a rational basis for engineering of transglycosylase activity.},
keywords = {agarase, Glycoside hydrolase, oligosaccharide synthesis, team 1, team 2, thesis, Transglycosylation, water dynamics},
pubstate = {published},
tppubtype = {article}
}
@article{Shahsavarian2017,
title = {Multitarget selection of catalytic antibodies with β-lactamase activity using phage display},
author = {Melody A Shahsavarian and Nancy Chaaya and Narciso Costa and Didier Boquet and Alexandre Atkinson and Bernard Offmann and Srini V Kaveri and Sébastien Lacroix-Desmazes and Alain Friboulet and Bérangère Avalle and Séverine Padiolleau-Lefèvre},
doi = {10.1111/febs.14012},
issn = {17424658},
year  = {2017},
date = {2017-01-01},
journal = {FEBS Journal},
volume = {284},
number = {4},
pages = {634--653},
abstract = {β-lactamase enzymes responsible for bacterial resistance to antibiotics are among the most important health threats to the human population today. Understanding the increasingly vast structural motifs responsible for the catalytic mechanism of β-lactamases will help improve the future design of new generation antibiotics and mechanism-based inhibitors of these enzymes. Here we report the construction of a large murine single chain fragment variable (scFv) phage display library of size 2.7 × 109 with extended diversity by combining different mouse models. We have used two molecularly different inhibitors of the R-TEM β-lactamase as targets for selection of catalytic antibodies with β-lactamase activity. This novel methodology has led to the isolation of five antibody fragments, which are all capable of hydrolyzing the β-lactam ring. Structural modeling of the selected scFv has revealed the presence of different motifs in each of the antibody fragments potentially responsible for their catalytic activity. Our results confirm (a) the validity of using our two target inhibitors for the in vitro selection of catalytic antibodies endowed with β-lactamase activity, and (b) the plasticity of the β-lactamase active site responsible for the wide resistance of these enzymes to clinically available inhibitors and antibiotics.},
keywords = {catalytic antibody, enzyme inhibitor, phage display, scFv library, team 1, β-lactamase},
pubstate = {published},
tppubtype = {article}
}
@article{Dion2017a,
title = {Development of a Sensitive Microarray Platform for the Ranking of Galectin Inhibitors: Identification of a Selective Galectin-3 Inhibitor},
author = {Johann Dion and Tamara Advedissian and Nataliya Storozhylova and Samir Dahbi and Annie Lambert and Frédérique Deshayes and Mireille Viguier and Charles Tellier and Françoise Poirier and Stéphane Téletchéa and Christophe Dussouy and Hiroaki Tateno and Jun Hirabayashi and Cyrille Grandjean},
doi = {10.1002/cbic.201700544},
issn = {14397633},
year  = {2017},
date = {2017-01-01},
journal = {ChemBioChem},
volume = {18},
number = {24},
pages = {2428--2440},
abstract = {Glycan microarrays are useful tools for lectin glycan profiling. The use of a glycan microarray based on evanescent-field fluorescence detection was herein further extended to the screening of lectin inhibitors in competitive experiments. The efficacy of this approach was tested with 2/3′-mono- and 2,3′-diaromatic type II lactosamine derivatives and galectins as targets and was validated by comparison with fluorescence anisotropy proposed as an orthogonal protein interaction measurement technique. We showed that subtle differences in the architecture of the inhibitor could be sensed that pointed out the preference of galectin-3 for 2′-arylamido derivatives over ureas, thioureas, and amines and that of galectin-7 for derivatives bearing an α substituent at the anomeric position of glucosamine. We eventually identified a diaromatic oxazoline as a highly specific inhibitor of galectin-3 versus galectin-1 and galectin-7.},
keywords = {binding studies, fluorescence polarization, galectin, inhibitors, Lactosamine, microarrays, team 1, team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{pmid27894960,
title = {Cancer stem cells in osteosarcoma},
author = {Hannah K Brown and Marta Tellez-Gabriel and Dominique Heymann},
doi = {10.1016/j.canlet.2016.11.019},
issn = {1872-7980},
year  = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
journal = {Cancer Lett},
volume = {386},
pages = {189--195},
abstract = {Osteosarcoma is the most common primary bone tumour in children and adolescents and advanced osteosarcoma patients with evidence of metastasis share a poor prognosis. Osteosarcoma frequently gains resistance to standard therapies highlighting the need for improved treatment regimens and identification of novel therapeutic targets. Cancer stem cells (CSC) represent a sub-type of tumour cells attributed to critical steps in cancer including tumour propagation, therapy resistance, recurrence and in some cases metastasis. Recent published work demonstrates evidence of cancer stem cell phenotypes in osteosarcoma with links to drug resistance and tumorigenesis. In this review we will discuss the commonly used isolation techniques for cancer stem cells in osteosarcoma as well as the identified biochemical and molecular markers.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{avEQ5:DELAVAT:2017aa,
title = {The hidden life of integrative and conjugative elements},
author = {François Delavat and Ryo Miyazaki and Nicolas Carraro and Nicolas Pradervand and Jan Roelof van der Meer},
doi = {10.1093/femsre/fux008},
year  = {2017},
date = {2017-01-01},
journal = {FEMS Microbiol Rev},
volume = {41},
number = {4},
pages = {512-537},
abstract = {Integrative and conjugative elements (ICEs) are widespread mobile DNA that transmit both vertically, in a host-integrated state, and horizontally, through excision and transfer to new recipients. Different families of ICEs have been discovered with more or less restricted host ranges, which operate by similar mechanisms but differ in regulatory networks, evolutionary origin and the types of variable genes they contribute to the host. Based on reviewing recent experimental data, we propose a general model of ICE life style that explains the transition between vertical and horizontal transmission as a result of a bistable decision in the ICE-host partnership. In the large majority of cells, the ICE remains silent and integrated, but hidden at low to very low frequencies in the population specialized host cells appear in which the ICE starts its process of horizontal transmission. This bistable process leads to host cell differentiation, ICE excision and transfer, when suitable recipients are present. The ratio of ICE bistability (i.e. ratio of horizontal to vertical transmission) is the outcome of a balance between fitness costs imposed by the ICE horizontal transmission process on the host cell, and selection for ICE distribution (i.e. ICE 'fitness'). From this emerges a picture of ICEs as elements that have adapted to a mostly confined life style within their host, but with a very effective and dynamic transfer from a subpopulation of dedicated cells.},
keywords = {Bistability, cellular differentiation, fitness cost, Horizontal gene transfer, out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{EQ2:LAMBERT:2017,
title = {Regulation of Differentiation of Nitrogen-Fixing Bacteria by Microsymbiont Targeting of Plant Thioredoxin s1},
author = {Carolina Werner Ribeiro and Fabien Baldacci-Cresp and Olivier Pierre and Marie Larousse and Sofiane Benyamina and Annie Lambert and Julie Hopkins and Claude Castella and Julie Cazareth and Geneviève Alloing and Eric Boncompagni and Jérémy Couturier and Peter Mergaert and Pascal Gamas and Nicolas Rouhier and Françoise Montrichard and Pierre Frendo},
url = {http://www.sciencedirect.com/science/article/pii/S0960982216313380},
doi = {https://doi.org/10.1016/j.cub.2016.11.013},
issn = {0960-9822},
year  = {2017},
date = {2017-01-01},
journal = {Current Biology},
volume = {27},
number = {2},
pages = {250 - 256},
abstract = {Summary 
Legumes associate with rhizobia to form nitrogen (N2)-fixing nodules, which is important for plant fitness [1, 2]. Medicago truncatula controls the terminal differentiation of Sinorhizobium meliloti into N2-fixing bacteroids by producing defensin-like nodule-specific cysteine-rich peptides (NCRs) [3, 4]. The redox state of NCRs influences some biological activities in free-living bacteria, but the relevance of redox regulation of NCRs in planta is unknown [5, 6], although redox regulation plays a crucial role in symbiotic nitrogen fixation [7, 8]. Two thioredoxins (Trx), Trx s1 and s2, define a new type of Trx and are expressed principally in nodules [9]. Here, we show that there are four Trx s genes, two of which, Trx s1 and s3, are induced in the nodule infection zone where bacterial differentiation occurs. Trx s1 is targeted to the symbiosomes, the N2-fixing organelles. Trx s1 interacted with NCR247 and NCR335 and increased the cytotoxic effect of NCR335 in S. meliloti. We show that Trx s silencing impairs bacteroid growth and endoreduplication, two features of terminal bacteroid differentiation, and that the ectopic expression of Trx s1 in S. meliloti partially complements the silencing phenotype. Thus, our findings show that Trx s1 is targeted to the bacterial endosymbiont, where it controls NCR activity and bacteroid terminal differentiation. Similarly, Trxs are critical for the activation of defensins produced against infectious microbes in mammalian hosts. Therefore, our results suggest the Trx-mediated regulation of host peptides as a conserved mechanism among symbiotic and pathogenic interactions.},
keywords = {bacteroids, differentiation, disulfide bond reduction, nitrogen-fixing symbiosis, nodule cysteine-rich peptides, out_lab, redox state, thiol modifications, thioredoxins},
pubstate = {published},
tppubtype = {article}
}
@article{EQ4:DUC:2017,
title = {The LINC complex contributes to heterochromatin organisation and transcriptional gene silencing in plants},
author = {Axel Poulet and Céline Duc and Maxime Voisin and Sophie Desset and Sylvie Tutois and Emmanuel Vanrobays and Matthias Benoit and David E Evans and Aline V Probst and Christophe Tatout},
url = {https://jcs.biologists.org/content/130/3/590},
doi = {10.1242/jcs.194712},
issn = {0021-9533},
year  = {2017},
date = {2017-01-01},
journal = {Journal of Cell Science},
volume = {130},
number = {3},
pages = {590--601},
publisher = {The Company of Biologists Ltd},
abstract = {The linker of nucleoskeleton and cytoskeleton (LINC) complex is an evolutionarily well-conserved protein bridge connecting the cytoplasmic and nuclear compartments across the nuclear membrane. While recent data support its function in nuclear morphology and meiosis, its involvement in chromatin organisation has not been studied in plants. Here, 3D imaging methods have been used to investigate nuclear morphology and chromatin organisation in interphase nuclei of the model plant Arabidopsis thaliana in which heterochromatin clusters in conspicuous chromatin domains called chromocentres. Chromocentres form a repressive chromatin environment contributing to transcriptional silencing of repeated sequences, a general mechanism needed for genome stability. Quantitative measurements of the 3D position of chromocentres indicate their close proximity to the nuclear periphery but that their position varies with nuclear volume and can be altered in specific mutants affecting the LINC complex. Finally, we propose that the plant LINC complex contributes to proper heterochromatin organisation and positioning at the nuclear periphery, since its alteration is associated with the release of transcriptional silencing as well as decompaction of heterochromatic sequences.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{EQ4:DUC:2017b,
title = {Arabidopsis ATRX Modulates H3.3 Occupancy and Fine-Tunes Gene Expression},
author = {Céline Duc and Matthias Benoit and Gwénaëlle Détourné and Lauriane Simon and Axel Poulet and Matthieu Jung and Alaguraj Veluchamy and David Latrasse and Samuel Le Goff and Sylviane Cotterell and Christophe Tatout and Moussa Benhamed and Aline V Probst},
url = {http://www.plantcell.org/content/29/7/1773},
doi = {10.1105/tpc.16.00877},
issn = {1040-4651},
year  = {2017},
date = {2017-01-01},
journal = {The Plant Cell},
volume = {29},
number = {7},
pages = {1773--1793},
publisher = {American Society of Plant Biologists},
abstract = {Histones are essential components of the nucleosome, the major chromatin subunit that structures linear DNA molecules and regulates access of other proteins to DNA. Specific histone chaperone complexes control the correct deposition of canonical histones and their variants to modulate nucleosome structure and stability. In this study, we characterize the Arabidopsis thaliana Alpha Thalassemia-mental Retardation X-linked (ATRX) ortholog and show that ATRX is involved in histone H3 deposition. Arabidopsis ATRX mutant alleles are viable, but show developmental defects and reduced fertility. Their combination with mutants of the histone H3.3 chaperone HIRA (Histone Regulator A) results in impaired plant survival, suggesting that HIRA and ATRX function in complementary histone deposition pathways. Indeed, ATRX loss of function alters cellular histone H3.3 pools and in consequence modulates the H3.1/H3.3 balance in the cell. H3.3 levels are affected especially at genes characterized by elevated H3.3 occupancy, including the 45S ribosomal DNA (45S rDNA) loci, where loss of ATRX results in altered expression of specific 45S rDNA sequence variants. At the genome-wide scale, our data indicate that ATRX modifies gene expression concomitantly to H3.3 deposition at a set of genes characterized both by elevated H3.3 occupancy and high expression. Together, our results show that ATRX is involved in H3.3 deposition and emphasize the role of histone chaperones in adjusting genome expression.GlossaryHUhydroxyureaChIPchromatin immunoprecipitationTEstransposable elementsGOGene OntologyRPKMreads per kilobase per million mapped readsNORnucleolus organizer region},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid28181304,
title = {Treatment of cutaneous and/or soft tissue manifestations of corticosteroids refractory chronic graft versus host disease (cGVHD) by a total nodal irradiation (TNI)},
author = {Guillaume Peyraga and Thibaut Lizee and Pierre Gustin and Karen Clement-Colmou and Christelle Di Bartolo and Stephane Supiot and Marc-Andre Mahe and Sylvie François and Martine Mege},
doi = {10.1111/ctr.12923},
issn = {1399-0012},
year  = {2017},
date = {2017-01-01},
urldate = {2017-01-01},
journal = {Clin Transplant},
volume = {31},
number = {4},
abstract = {The management of corticosteroids refractory chronic graft versus host disease (cGVHD) remains controversial. Retrospective analysis of patients treated at the Integrated Center of Oncology by total nodal irradiation (TNI) was performed to evaluate its therapy potency. TNI delivers a dose of 1 Gy in a single session. The delimitation of the fields is clinical (upper limit: external auditory meatus; lower limit: mid-femur). No pre-therapeutic dosimetry scanner was necessary. Evaluation of the efficacy was by clinical measures at 6 months after the treatment. Twelve patients were treated by TNI between January 2010 and December 2013. TNI was used in second-line treatment or beyond. The median time between allograft and TNI was 31.2 months, and the median time between the first manifestations of cGVHD and TNI was about 24.2 months. Of the 12 patients, nine had a clinical response at 6 months (75%), including five complete clinical responses (41.6%). Five patients could benefit from a reduction of corticosteroid doses. Three patients had hematologic toxicity. TNI could be considered as an option for the treatment of a cutaneous and/or soft tissues corticosteroids refractory cGVHD. However, prospective randomized and double-blind trials remain essential to answer the questions about TNI safety and effectiveness.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Thiriet-Rupert2016,
title = {Transcription factors in microalgae: genome-wide prediction and comparative analysis},
author = {Stanislas Thiriet-Rupert and Grégory Carrier and Benoît Chénais and Camille Trottier and Gaël Bougaran and Jean-Paul Cadoret and Benoît Schoefs and Bruno Saint-Jean},
url = {http://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-016-2610-9},
doi = {10.1186/s12864-016-2610-9},
issn = {1471-2164},
year  = {2016},
date = {2016-12-01},
journal = {BMC Genomics},
volume = {17},
number = {1},
pages = {282},
publisher = {BioMed Central},
abstract = {Studying transcription factors, which are some of the key players in gene expression, is of outstanding interest for the investigation of the evolutionary history of organisms through lineage-specific features. In this study we performed the first genome-wide TF identification and comparison between haptophytes and other algal lineages. For TF identification and classification, we created a comprehensive pipeline using a combination of BLAST, HMMER and InterProScan software. The accuracy evaluation of the pipeline shows its applicability for every alga, plant and cyanobacterium, with very good PPV and sensitivity. This pipeline allowed us to identify and classified the transcription factor complement of the three haptophytes Tisochrysis lutea, Emiliania huxleyi and Pavlova sp.; the two stramenopiles Phaeodactylum tricornutum and Nannochloropsis gaditana; the chlorophyte Chlamydomonas reinhardtii and the rhodophyte Porphyridium purpureum. By using T. lutea and Porphyridium purpureum, this work extends the variety of species included in such comparative studies, allowing the detection and detailed study of lineage-specific features, such as the presence of TF families specific to the green lineage in Porphyridium purpureum, haptophytes and stramenopiles. Our comprehensive pipeline also allowed us to identify fungal and cyanobacterial TF families in the algal nuclear genomes. This study provides examples illustrating the complex evolutionary history of algae, some of which support the involvement of a green alga in haptophyte and stramenopile evolution.},
keywords = {Animal Genetics and Genomics, general, Life Sciences, microarrays, Microbial Genetics and Genomics, out_lab, Plant Genetics {&amp;} Genomics, Proteomics},
pubstate = {published},
tppubtype = {article}
}
@article{pmid27853299,
title = {The archaeal 7 kDa DNA-binding proteins: extended characterization of an old gifted family},
author = {Valentina Kalichuk and Ghislaine Béhar and Axelle Renodon-Cornière and Georgi Danovski and Gonzalo Obal and Jacques Barbet and Barbara Mouratou and Frédéric Pecorari},
doi = {10.1038/srep37274},
issn = {2045-2322},
year  = {2016},
date = {2016-11-17},
urldate = {2016-11-17},
journal = {Sci Rep},
volume = {6},
pages = {37274},
abstract = {The "7 kDa DNA-binding" family, also known as the Sul7d family, is composed of chromatin proteins from the Sulfolobales archaeal order. Among them, Sac7d and Sso7d have been the focus of several studies with some characterization of their properties. Here, we studied eleven other proteins alongside Sac7d and Sso7d under the same conditions. The dissociation constants of the purified proteins for binding to double-stranded DNA (dsDNA) were determined in phosphate-buffered saline at 25 °C and were in the range from 11 μM to 22 μM with a preference for G/C rich sequences. In accordance with the extremophilic origin of their hosts, the proteins were found highly stable from pH 0 to pH 12 and at temperatures from 85.5 °C to 100 °C. Thus, these results validate eight putative "7 kDa DNA-binding" family proteins and show that they behave similarly regarding both their function and their stability among various genera and species. As Sac7d and Sso7d have found numerous uses as molecular biology reagents and artificial affinity proteins, this study also sheds light on even more attractive proteins that will facilitate engineering of novel highly robust reagents.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{avEQ5:Rastogi_TIRICHINE:2016,
title = {PhytoCRISP-Ex: a web-based and stand-alone application to find specific target sequences for CRISPR/CAS editing},
author = {Achal Rastogi and Omer Murik and Chris Bowler and Leila Tirichine},
url = {https://doi.org/10.1186%2Fs12859-016-1143-1},
doi = {10.1186/s12859-016-1143-1},
year  = {2016},
date = {2016-07-01},
journal = {BMC Bioinformatics},
volume = {17},
number = {1},
publisher = {Springer Science and Business Media LLC},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Silva2016,
title = {Rapid diminution in the level and activity of DNA-dependent protein kinase in cancer cells by a reactive nitro-benzoxadiazole compound},
author = {Viviane A O Silva and Florian Lafont and Houda Benhelli-Mokrani and Magali {Le Breton} and Philippe Hulin and Thomas Chabot and Fran{ç}ois Paris and Vehary Sakanyan and Fabrice Fleury},
doi = {10.3390/ijms17050703},
issn = {14220067},
year  = {2016},
date = {2016-05-01},
journal = {International Journal of Molecular Sciences},
volume = {17},
number = {5},
publisher = {MDPI AG},
abstract = {The expression and activity of DNA-dependent protein kinase (DNA-PK) is related to DNA repair status in the response of cells to exogenous and endogenous factors. Recent studies indicate that Epidermal Growth Factor Receptor (EGFR) is involved in modulating DNA-PK. It has been shown that a compound 4-nitro-7-[(1-oxidopyridin-2-yl)sulfanyl]-2,1,3-benzoxadiazole (NSC), bearing a nitro-benzoxadiazole (NBD) scaffold, enhances tyrosine phosphorylation of EGFR and triggers downstream signaling pathways. Here, we studied the behavior of DNA-PK and other DNA repair proteins in prostate cancer cells exposed to compound NSC. We showed that both the expression and activity of DNA-PKcs (catalytic subunit of DNA-PK) rapidly decreased upon exposure of cells to the compound. The decline in DNA-PKcs was associated with enhanced protein ubiquitination, indicating the activation of cellular proteasome. However, pretreatment of cells with thioglycerol abolished the action of compound NSC and restored the level of DNA-PKcs. Moreover, the decreased level of DNA-PKcs was associated with the production of intracellular hydrogen peroxide by stable dimeric forms of Cu/Zn SOD1 induced by NSC. Our findings indicate that reactive oxygen species and electrophilic intermediates, generated and accumulated during the redox transformation of NBD compounds, are primarily responsible for the rapid modulation of DNA-PKcs functions in cancer cells.},
keywords = {Chemiosensitization, DNA repair, DNA-PKcs, Hydrogen peroxide, Nitro-benzoxadiazole, Prostate cancer, Protein targeting, SOD1, team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Liu2016,
title = {Biotype characterization, developmental profiling, insecticide response and binding property of Bemisia tabaci chemosensory proteins: Role of CSP in insect defense},
author = {Guoxia Liu and Hongmei Ma and Hongyan Xie and Ning Xuan and Xia Guo and Zhongxue Fan and Balaji Rajashekar and Philippe Arnaud and Bernard Offmann and Jean François Picimbon},
doi = {10.1371/journal.pone.0154706},
issn = {19326203},
year  = {2016},
date = {2016-05-01},
journal = {PLoS ONE},
volume = {11},
number = {5},
publisher = {Public Library of Science},
abstract = {Chemosensory proteins (CSPs) are believed to play a key role in the chemosensory process in insects. Sequencing genomic DNA and RNA encoding CSP1, CSP2 and CSP3 in the sweet potato whitefly Bemisia tabaci showed strong variation between B and Q biotypes. Analyzing CSP-RNA levels showed not only biotype, but also age and developmental stage-specific expression. Interestingly, applying neonicotinoid thiamethoxam insecticide using twenty-five different dose/time treatments in B and Q young adults showed that Bemisia CSP1, CSP2 and CSP3 were also differentially regulated over insecticide exposure. In our study one of the adult-specific gene (CSP1) was shown to be significantly up-regulated by the insecticide in Q, the most highly resistant form of B. tabaci. Correlatively, competitive binding assays using tryptophan fluorescence spectroscopy and molecular docking demonstrated that CSP1 protein preferentially bound to linoleic acid, while CSP2 and CSP3 proteins rather associated to another completely different type of chemical, i.e. α-pentyl-cinnamaldehyde (jasminaldehyde). This might indicate that some CSPs in whiteflies are crucial to facilitate the transport of fatty acids thus regulating some metabolic pathways of the insect immune response, while some others are tuned to much more volatile chemicals known not only for their pleasant odor scent, but also for their potent toxic insecticide activity.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{pmid26952369,
title = {Affitins as robust tailored reagents for affinity chromatography purification of antibodies and non-immunoglobulin proteins},
author = {Ghislaine Béhar and Axelle Renodon-Cornière and Barbara Mouratou and Frédéric Pecorari},
doi = {10.1016/j.chroma.2016.02.068},
issn = {1873-3778},
year  = {2016},
date = {2016-04-08},
urldate = {2016-04-01},
journal = {J Chromatogr A},
volume = {1441},
pages = {44--51},
abstract = {Affinity chromatography is a convenient way of purifying proteins, as a high degree of purity can be reached in one step. The use of tags has greatly contributed to the popularity of this technique. However, the addition of tags may not be desirable or possible for the production of biopharmaceuticals. There is thus a need for tailored artificial affinity ligands. We have developed the use of archaeal extremophilic proteins as scaffolds to generate affinity proteins (Affitins). Here, we explored the potential of Affitins as ligand to design affinity columns. Affitins specific for human immunoglobulin G (hIgG), bacterial PulD protein, and chicken egg lysozyme were immobilized on an agarose matrix. The columns obtained were functional and highly selective for their cognate target, even in the presence of exogenous proteins as found in cell culture media, ascites and bacterial lysates, which result in a high degree of purity (∼95%) and recovery (∼100%) in a single step. Anti-hIgG Affitin columns withstand repetitive cycles of purification and cleaning-in-place treatments with 0.25 M NaOH as well as Protein A does. High levels of Affitin productions in Escherichia coli makes it possible to produce these affinity columns at low cost. Our results validate Affitins as a new class of tailored ligands for the affinity chromatography purification of potentially any proteins of interest including biopharmaceuticals.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid26909338,
title = {Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer},
author = {Alan Dal Pra and Jennifer A Locke and Gerben Borst and Stephane Supiot and Robert G Bristow},
doi = {10.3389/fonc.2016.00024},
issn = {2234-943X},
year  = {2016},
date = {2016-02-16},
urldate = {2016-01-01},
journal = {Front Oncol},
volume = {6},
pages = {24},
abstract = {Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. },
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid27536556,
title = {Comparison of Automated Atlas-Based Segmentation Software for Postoperative Prostate Cancer Radiotherapy},
author = {Grégory Delpon and Alexandre Escande and Timothée Ruef and Julien Darréon and Jimmy Fontaine and Caroline Noblet and Stéphane Supiot and Thomas Lacornerie and David Pasquier},
doi = {10.3389/fonc.2016.00178},
issn = {2234-943X},
year  = {2016},
date = {2016-01-01},
urldate = {2016-01-01},
journal = {Front Oncol},
volume = {6},
pages = {178},
abstract = {Automated atlas-based segmentation (ABS) algorithms present the potential to reduce the variability in volume delineation. Several vendors offer software that are mainly used for cranial, head and neck, and prostate cases. The present study will compare the contours produced by a radiation oncologist to the contours computed by different automated ABS algorithms for prostate bed cases, including femoral heads, bladder, and rectum. Contour comparison was evaluated by different metrics such as volume ratio, Dice coefficient, and Hausdorff distance. Results depended on the volume of interest showed some discrepancies between the different software. Automatic contours could be a good starting point for the delineation of organs since efficient editing tools are provided by different vendors. It should become an important help in the next few years for organ at risk delineation. },
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pauty2016investigation,
title = {Investigation of the DNA damage response to SFOM-0046, a new small-molecule drug inducing DNA double-strand breaks},
author = {Joris Pauty and Marie-France Côté and Amélie Rodrigue and Denis Velic and Jean-Yves Masson and Sébastien Fortin},
url = {https://www.nature.com/articles/srep23302},
doi = {10.1038/srep23302},
year  = {2016},
date = {2016-01-01},
journal = {Scientific reports},
volume = {6},
number = {1},
pages = {1--11},
publisher = {Nature Publishing Group},
abstract = {2-Ethylphenyl 4-(3-ethylureido)benzenesulfonate (SFOM-0046) is a novel anticancer agent that arrests cell cycle in S-phase and causes DNA replication stress leading to the phosphorylation of H2AX into γ-H2AX. First, using the M21, HT29, HT-1080 and HeLa cell lines, we confirmed that S-phase cell cycle arrest and γ-H2AX foci induction by SFOM-0046 is a general mechanism occurring in diverse cancer cell lines. In addition to γ-H2AX, SFOM-0046 activates preferentially ATR-Chk1 in M21 and HT29 cells while both ATR-Chk1 and ATM-Chk2 pathways are activated in HCT116 cells. Co-localization of SFOM-0046-induced 53BP1 foci with γ-H2AX foci validates that the DNA damage generated corresponds to double-strand-breaks (DSBs). Consistent with an S-phase arrest, SFOM-0046 treatment induces RAD51 foci formation but not DNA-PKcs foci, confirming that homologous recombination is the major DSB repair pathway targeted by the drug. Furthermore, using isogenic HCT116 p53+/+ and HCT116 p53−/− cells, we showed that p53 plays a key role in the survival mechanism to SFOM-0046. Finally, SFOM-0046 exhibits a dose-dependent antitumor activity on human fibrosarcoma HT-1080 tumours grafted onto chick chorioallantoic membranes without showing embryo toxicity even at high doses. Altogether, our results highlight SFOM-0046 as a very promising drug that induces a replication stress response.},
keywords = {out_lab, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{Krylov2016,
title = {Well-Known Mediators of Selective Oxidation with Unknown Electronic Structure: Metal-Free Generation and EPR Study of Imide-N-oxyl Radicals},
author = {Igor B Krylov and Mykhailo O Kompanets and Katerina V Novikova and Iosip O Opeida and Olga V Kushch and Boris N Shelimov and Gennady I Nikishin and Dmitri O Levitsky and Alexander O Terent'ev},
doi = {10.1021/acs.jpca.5b10722},
issn = {15205215},
year  = {2016},
date = {2016-01-01},
journal = {Journal of Physical Chemistry A},
volume = {120},
number = {1},
pages = {68--73},
abstract = {Nitroxyl radicals are widely used in chemistry, materials sciences, and biology. Imide-N-oxyl radicals are subclass of unique nitroxyl radicals that proved to be useful catalysts and mediators of selective oxidation and CH-functionalization. An efficient metal-free method was developed for the generation of imide-N-oxyl radicals from N-hydroxyimides at room temperature by the reaction with (diacetoxyiodo)benzene. The method allows for the production of high concentrations of free radicals and provides high resolution of their EPR spectra exhibiting the superhyperfine structure from benzene ring protons distant from the radical center. An analysis of the spectra shows that, regardless of the electronic effects of the substituents in the benzene ring, the superhyperfine coupling constant of an unpaired electron with the distant protons at positions 4 and 5 of the aromatic system is substantially greater than that with the protons at positions 3 and 6 that are closer to the N-oxyl radical center. This is indicative of an unusual character of the spin density distribution of the unpaired electron in substituted phthalimide-N-oxyl radicals. Understanding of the nature of the electron density distribution in imide-N-oxyl radicals may be useful for the development of commercial mediators of oxidation based on N-hydroxyimides.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Mansuroglu2016,
title = {Loss of Tau protein affects the structure, transcription and repair of neuronal pericentromeric heterochromatin},
author = {Zeyni Mansuroglu and Houda Benhelli-Mokrani and Vasco Marcato and Audrey Sultan and Marie Violet and Alban Chauderlier and Lucie Delattre and Anne Loyens and Smail Talahari and Séverine Bégard and Fabrice Nesslany and Morvane Colin and Sylvie Souès and Bruno Lefebvre and Luc Buée and Marie Christine Galas and Eliette Bonnefoy},
doi = {10.1038/srep33047},
issn = {20452322},
year  = {2016},
date = {2016-01-01},
journal = {Scientific Reports},
volume = {6},
number = {September},
pages = {1--16},
publisher = {Nature Publishing Group},
abstract = {Pericentromeric heterochromatin (PCH) gives rise to highly dense chromatin sub-structures rich in the epigenetic mark corresponding to the trimethylated form of lysine 9 of histone H3 (H3K9me3) and in heterochromatin protein 1α (HP1α), which regulate genome expression and stability. We demonstrate that Tau, a protein involved in a number of neurodegenerative diseases including Alzheimer's disease (AD), binds to and localizes within or next to neuronal PCH in primary neuronal cultures from wild-type mice. Concomitantly, we show that the clustered distribution of H3K9me3 and HP1α, two hallmarks of PCH, is disrupted in neurons from Tau-deficient mice (KOTau). Such altered distribution of H3K9me3 that could be rescued by overexpressing nuclear Tau protein was also observed in neurons from AD brains. Moreover, the expression of PCH non-coding RNAs, involved in PCH organization, was disrupted in KOTau neurons that displayed an abnormal accumulation of stress-induced PCH DNA breaks. Altogether, our results demonstrate a new physiological function of Tau in directly regulating neuronal PCH integrity that appears disrupted in AD neurons.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Jaunet-Lahary2016,
title = {A Joint Theoretical and Experimental Study of the Behavior of the DIDS Inhibitor and its Derivatives},
author = {Titouan Jaunet-Lahary and Anaïs Goupille and Denis Jacquemin and Fabrice Fleury and Jérôme Graton and Adèle D Laurent},
doi = {10.1002/cphc.201600107},
issn = {14397641},
year  = {2016},
date = {2016-01-01},
journal = {ChemPhysChem},
volume = {3},
pages = {2434--2445},
abstract = {4,4′-Diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) is a well-known ion-exchange inhibitor targeting cardiac functions and indirectly impeding both radio- and chemo-resistance. A joint computational and experimental study is presented to provide deeper insights into DIDS and other members of this family of compounds. To this end, we applied state-of-the-art density functional theory (DFT) and time-dependent DFT methods, in addition to measuring the optical properties. The experimental data show that such compounds are highly sensitive to their environment and that the optical properties change within as little time as 7 h. However, the optical properties of DIDS are similar in various acidic/basic environments, which were confirmed by pKa computations on both cis and trans isomers. The protonation analysis also highlights that the singly protonated form of DIDS behaves like a proton sponge compound. The experimentally observed redshift that can be seen when going from water to DMSO was reproduced solely by using the solvation model based on density, although the polarization continuum model and implicit/explicit hybrid schemes were also tested. The characteristic broadening of the absorption peak in water and the vibronic fine structure in DMSO were also reproduced thanks to vibronic coupling simulations associated with the solvent reorganization energy. For other stilbene derivatives, a correlation is found between the maximum absorption wavelength and the Hammett parameters.},
keywords = {density functional calculations, solvent reorganization, stilbene sulfonic acid, team 3, thesis, UV/Vis spectroscopy, vibronic couplings},
pubstate = {published},
tppubtype = {article}
}
@article{TerentEv2016,
title = {Selective transformation of tricyclic peroxides with pronounced antischistosomal activity into 2-hydroxy-1,5-diketones using iron (II) salts},
author = {Alexander O Terent'Ev and Zhanna Yu Pastukhova and Ivan A Yaremenko and Roman A Novikov and Dmitry V Demchuk and Lev G Bruk and Dmitri O Levitsky and Fabrice Fleury and Gennady I Nikishin},
url = {http://dx.doi.org/10.1016/j.tet.2016.04.054},
doi = {10.1016/j.tet.2016.04.054},
issn = {14645416},
year  = {2016},
date = {2016-01-01},
journal = {Tetrahedron},
volume = {72},
number = {24},
pages = {3421--3426},
publisher = {Elsevier Ltd},
abstract = {The present work deals with selective transformations of peroxides into organic compounds via the cleavage of the O-O bond using variable valence metals. A selective transformation of tricyclic peroxides promoted by Fe2+ salts was discovered. This selective transformation is unexpected for compounds with structural features which allow diverse decomposition pathways. 2-Hydroxy-1,5-diketones are prepared in yields up to 92% in the reactions of tricyclic peroxides with FeSO4, Fe(ClO4)2, or FeCl2. This is a new preparative method for the synthesis of 1,5-diketones. 2-Hydroxy-1,5-diketones in CDCl3 at 25 °C exist mainly in the open-chain form of the hydroxyketone over the cyclic hemiacetal. The results of this work can be of interest to understand the mechanism of the antiparasitic action of peroxides.},
keywords = {Antiparasitic, Cycles, Diketones, Iron (II) salts, Peroxides, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Levitsky2016,
title = {Mathews Journal of Pharmaceutical Science Naturally Occurring Isocyano / Isothiocyanato Compounds : Their Pharmacological and SAR Activities},
author = {Dmitri O Levitsky and Tatyana A Gloriozova and Vladimir V Poroikov and Valery M Dembitsky},
year  = {2016},
date = {2016-01-01},
journal = {MATHEWS, Open Access Journals},
volume = {1},
number = {1},
pages = {1--15},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Zdvizhkov2016,
title = {Transformation of 2-allyl-1,3-diketones to bicyclic compounds containing 1,2-dioxolane and tetrahydrofuran rings using the I2/H2O2 system},
author = {Alexander T Zdvizhkov and Alexander O Terent'Ev and Peter S Radulov and Roman A Novikov and Viktor A Tafeenko and Vladimir V Chernyshev and Alexey I Ilovaisky and Dmitri O Levitsky and Fabrice Fleury and Gennady I Nikishin},
url = {http://dx.doi.org/10.1016/j.tetlet.2016.01.061},
doi = {10.1016/j.tetlet.2016.01.061},
issn = {18733581},
year  = {2016},
date = {2016-01-01},
journal = {Tetrahedron Letters},
volume = {57},
number = {8},
pages = {949--952},
publisher = {Elsevier Ltd},
abstract = {A one-pot procedure was developed for the assembly of bicyclic compounds containing 1,2-dioxolane and tetrahydrofuran rings based on the reaction of 2-allyl-1,3-diketones with the I2/H2O2 system. A fivefold molar excess of H2O2 and a twofold excess of I2 are required for the selective formation of tetrahydrofurodioxoles. The synthesis of these structurally complex molecules is unusual in that it does not produce the expected bridged tetraoxanes, products of the addition of several H2O2 molecules to a carbonyl group, or the products of double bond iodoperoxidation.},
keywords = {Cyclization, Hydrogen peroxide, Iodination, Iodine, Peroxides, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Sakanyan2016,
title = {Activation of EGFR by small compounds through coupling the generation of hydrogen peroxide to stable dimerization of Cu/Zn SOD1},
author = {Vehary Sakanyan and Philippe Hulin and Rodolphe {Alves De Sousa} and Viviane A O Silva and Artur Hambardzumyan and Steven Nedellec and Christophe Tomasoni and Cédric Logé and Charles Pineau and Christos Roussakis and Fabrice Fleury and Isabelle Artaud},
url = {http://dx.doi.org/10.1038/srep21088},
doi = {10.1038/srep21088},
issn = {20452322},
year  = {2016},
date = {2016-01-01},
journal = {Scientific Reports},
volume = {6},
number = {January},
pages = {1--14},
publisher = {Nature Publishing Group},
abstract = {Activation of cell signaling by reactive chemicals and pollutants is an important issue for human health. It has been shown that lipophilic nitro-benzoxadiazole (NBD) compounds rapidly move across the plasma membrane and enhance Epidermal Growth Factor Receptor (EGFR) tyrosine phosphorylation in cancer cells. Unlike ligand-dependent activation, the mechanism of this induction relies on the generation of hydrogen peroxide, which is involved in the activation of the catalytic site of the receptor and the inactivation of protein tyrosine phosphatase PTP-1B. Production of H 2 O 2 during redox transformation of NBD compounds is associated with the transition of a monomeric form of Cu/Zn superoxide dismutase 1 (SOD1) to stable dimers. The highly stable and functionally active SOD1 dimer, in the absence of adequate activities in downstream reactions, promotes the disproportionate production and accumulation of intracellular hydrogen peroxide shortly after exposure to NBD compounds. The intrinsic fluorescence of small compounds was used to demonstrate their binding to SOD1. Our data indicate that H 2 O 2 and concomitantly generated electrophilic intermediates behave as independent entities, but all contribute to the biological reactivity of NBD compounds. This study opens a promising path to identify new biomarkers of oxidative/electrophilic stress in the progression of cancer and other diseases.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Faucon2016,
title = {Tuning the architectural integrity of high-performance magneto-fluorescent core-shell nanoassemblies in cancer cells},
author = {Adrien Faucon and Houda Benhelli-Mokrani and Fabrice Fleury and Laurence Dubreil and Philippe Hulin and Steven Nedellec and Tristan Doussineau and Rodolphe Antoine and Tomas Orlando and Alessandro Lascialfari and Jér{ô}me Fresnais and Léna{ï}c Lartigue and Eléna Ishow},
url = {http://dx.doi.org/10.1016/j.jcis.2016.06.064},
doi = {10.1016/j.jcis.2016.06.064},
issn = {10957103},
year  = {2016},
date = {2016-01-01},
journal = {Journal of Colloid and Interface Science},
volume = {479},
pages = {139--149},
publisher = {Elsevier Inc.},
abstract = {High-density nanoarchitectures, endowed with simultaneous fluorescence and contrast properties for MRI and TEM imaging, have been obtained using a simple self-assembling strategy based on supramolecular interactions between non-doped fluorescent organic nanoparticles (FON) and superparamagnetic nanoparticles. In this way, a high-payload core-shell structure FON@mag has been obtained, protecting the hydrophobic fluorophores from the surroundings as well as from emission quenching by the shell of magnetic nanoparticles. Compared to isolated nanoparticles, maghemite nanoparticles self-assembled as an external shell create large inhomogeneous magnetic field, which causes enhanced transverse relaxivity and exacerbated MRI contrast. The magnetic load of the resulting nanoassemblies is evaluated using magnetic sedimentation and more originally electrospray mass spectrometry. The role of the stabilizing agents (citrate versus polyacrylate anions) revealed to be crucial regarding the cohesion of the resulting high-performance magneto-fluorescent nanoassemblies, which questions their use after cell internalization as nanocarriers or imaging agents for reliable correlative light and electron microcopy.},
keywords = {Bioimaging, Core-shell structure, Fluorescent organic nanoparticles, Magnetism, Magneto-fluorescent nanoassemblies, Supraparticles, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Forato2016,
title = {Comparison of Zirconium Phosphonate-Modified Surfaces for Immobilizing Phosphopeptides and Phosphate-Tagged Proteins},
author = {Florian Forato and Hao Liu and Roland Benoit and Franck Fayon and Cathy Charlier and Amina Fateh and Alain Defontaine and Charles Tellier and Daniel R Talham and Clémence Queffélec and Bruno Bujoli},
doi = {10.1021/acs.langmuir.6b01020},
issn = {15205827},
year  = {2016},
date = {2016-01-01},
journal = {Langmuir},
volume = {32},
number = {22},
pages = {5480--5490},
abstract = {Different routes for preparing zirconium phosphonate-modified surfaces for immobilizing biomolecular probes are compared. Two chemical-modification approaches were explored to form self-assembled monolayers on commercially available primary amine-functionalized slides, and the resulting surfaces were compared to well-characterized zirconium phosphonate monolayer-modified supports prepared using Langmuir-Blodgett methods. When using POCl3 as the amine phosphorylating agent followed by treatment with zirconyl chloride, the result was not a zirconium-phosphonate monolayer, as commonly assumed in the literature, but rather the process gives adsorbed zirconium oxide/hydroxide species and to a lower extent adsorbed zirconium phosphate and/or phosphonate. Reactions giving rise to these products were modeled in homogeneous-phase studies. Nevertheless, each of the three modified surfaces effectively immobilized phosphopeptides and phosphopeptide tags fused to an affinity protein. Unexpectedly, the zirconium oxide/hydroxide modified surface, formed by treating the amine-coated slides with POCl3/Zr4+, afforded better immobilization of the peptides and proteins and efficient capture of their targets.},
keywords = {impact, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{RN16,
title = {Phenotypical and biochemical characterisation of resistance for parasitic weed (Orobanche foetida Poir.) in radiation-mutagenised mutants of chickpea},
author = {Ines Brahmi and Yassine Mabrouk and Guillaume Brun and Philippe Delavault and Omrane Belhadj and Philippe Simier},
url = {https://onlinelibrary.wiley.com/doi/10.1002/ps.4278},
doi = {10.1002/ps.4278},
issn = {1526-498x},
year  = {2016},
date = {2016-01-01},
urldate = {2016-01-01},
journal = {Pest Manag Sci},
volume = {72},
number = {12},
pages = {2330-2338},
abstract = {BACKGROUND: Some radiation-mutagenised chickpea mutants potentially resistant to the broomrape, Orobanche foetida Poir., were selected through field trials. The objectives of this work were to confirm resistance under artificial infestation, in pots and mini-rhizotron systems, and to determine the developmental stages of broomrape affected by resistance and the relevant resistance mechanisms induced by radiation mutagenesis. RESULTS: Among 30 mutants tested for resistance to O. foetida, five shared strong resistance in both pot experiments and mini-rhizotron systems. Resistance was not complete, but the few individuals that escaped resistance displayed high disorders of shoot development. Results demonstrated a 2-3-fold decrease in stimulatory activity of root exudates towards broomrape seed germination in resistant mutants in comparison with non-irradiated control plants and susceptible mutants. Resistance was associated with an induction of broomrape necrosis early during infection. When infested, most of the resistant mutants shared enhanced levels of soluble phenolic contents, phenylalanine ammonia lyase activity, guaiacol peroxidase activity and polyphenol oxidase activity, in addition to glutathione and notably ascorbate peroxidase gene expression in roots. CONCLUSION: Results confirmed enhanced resistance in chickpea radiation-mutagenised mutants, and demonstrated that resistance is based on alteration of root exudation, presumed cell-wall reinforcement and change in root oxidative status in response to infection. © 2016 Society of Chemical Industry.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Goux2016,
title = {In vivo phosphorylation of a peptide tag for protein purification},
author = {Marine Goux and Amina Fateh and Alain Defontaine and Mathieu Cinier and Charles Tellier},
url = {https://doi.org/10.1007/s10529-016-2040-4},
doi = {10.1007/s10529-016-2040-4},
issn = {1573-6776},
year  = {2016},
date = {2016-01-01},
journal = {Biotechnology Letters},
volume = {38},
number = {5},
pages = {767--772},
abstract = {To design a new system for the in vivo phosphorylation of proteins in Escherichia coli using the co-expression of the α-subunit of casein kinase II (CKIIα) and a target protein, (Nanofitin) fused with a phosphorylatable tag.},
keywords = {team 2, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{RN23,
title = {New Insights into Phloem Unloading and Expression of Sucrose Transporters in Vegetative Sinks of the Parasitic Plant Phelipanche ramosa L. (Pomel)},
author = {Thomas Péron and Adrien Candat and Grégory Montiel and Christophe Veronesi and David Macherel and Philippe Delavault and Philippe Simier},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220101/pdf/fpls-07-02048.pdf},
doi = {10.3389/fpls.2016.02048},
issn = {1664-462X (Print) 1664-462x},
year  = {2016},
date = {2016-01-01},
urldate = {2016-01-01},
journal = {Front Plant Sci},
volume = {7},
pages = {2048},
abstract = {The plant-parasitic plant interaction is a interesting model to study sink-source relationship and phloem unloading. The parasitic plants, such as the achlorophyllous plant Phelipanche ramosa, connect to the host phloem through the haustorium and act as supernumerary sinks for the host-derived photoassimilates, primarily sucrose. The application of the fluorescent symplastic tracer, carboxyfluorescein (CF) derived from carboxyfluorescein diacetate (CFDA), to the leaves of the host plant (Brassica napus) showed direct phloem connections at the host-parasite interface. These experiments also evidenced the dominant apoplastic pathway for phloem unloading in major vegetative sinks of the parasite, including tubercles and shoots, except the adventitious root apices. The CF experiments showed also the symplastic isolation of the phloem tissues from the sink tissues in tubercle and shoot of the parasite, then suggesting the pivotal role of sucrose transporters in sucrose unloading in P. ramosa sinks. Three cDNAs encoding sucrose transporters (PrSUT) were isolated from the parasitic plant. PrSUT1 transcripts accumulated at the same level in the tubercle throughout the parasite growth while a significant increase in transcript accumulation occurred after emergence in the flowering shoot, notably in the growing apical part. The in situ hybridization experiments revealed the PrSUT1 transcript accumulation in the mature phloem cells of both subterranean and flowering shoots, as well as in shoot terminal sinks corresponding to apical meristem, scale leaf primordia and immature vasculature. The transient expression experiments in Arabidopsis protoplasts showed that PrSUT1 was localized at the plasma membrane, suggesting its role in phloem functioning and sucrose uptake by the sink cells in P. ramosa. Conversely, the PrSUT2 transcript accumulation was constantly low in tubercles and shoots but PrSUT3 transcripts accumulated markedly in the subterranean and flowering shoots, in concordance with the PrSUT3 mRNA accumulation in multiple sink areas including apical meristem, scale-leaf primordia, immature vasculature and even storage parenchyma. However, the PrSUT3 transcripts did not accumulate in the mature phloem cells. The transient expression experiments in Arabidopsis protoplasts suggested a tonoplast localization of PrSUT3, for which nevertheless the involvement in intracellular sucrose transport needs clarification.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{RN12,
title = {Molecular Identification of Broomrape Species from a Single Seed by High Resolution Melting Analysis},
author = {Mathieu Rolland and Aurélie Dupuy and Aude Pelleray and Philippe Delavault},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5149549/pdf/fpls-07-01838.pdf},
doi = {10.3389/fpls.2016.01838},
issn = {1664-462X (Print) 1664-462x},
year  = {2016},
date = {2016-01-01},
urldate = {2016-01-01},
journal = {Front Plant Sci},
volume = {7},
pages = {1838},
abstract = {Broomrapes are holoparasitic plants spreading through seeds. Each plant produces hundreds of thousands of seeds which remain viable in the soils for decades. To limit their spread, drastic measures are being taken and the contamination of a commercial seed lot by a single broomrape seed can lead to its rejection. Considering that broomrapes species identification from a single seed is extremely difficult even for trained botanists and that among all the described species, only a few are really noxious for the crops, numerous seed lots are rejected because of the contamination by seeds of non-noxious broomrape species. The aim of this study was to develop and evaluate a High Resolution Melting assay identifying the eight most noxious and common broomrape species (Phelipanche aegyptiaca, Orobanche cernua, O. crenata, O. cumana, O. foetida, O. hederae, O. minor, and P. ramosa) from a single seed. Based on trnL and rbcL plastidial genes amplification, the designed assay successfully identifies O. cumana, O. cernua, O. crenata, O. minor, O. hederae, and O. foetida; P. ramosa, and P. aegyptiaca can be differentiated from other species but not from each other. Tested on 50 seed lots, obtained results perfectly matched identifications performed by sequencing. Through the analysis of common seed lots by different analysts, the reproducibility of the assay was evaluated at 90%. Despite an original sample preparation process it was not possible to extract enough DNA from some seeds (10% of the samples). The described assay fulfills its objectives and allows an accurate identification of the targeted broomrape species. It can be used to identify contaminants in commercial seed lots or for any other purpose. The assay might be extended to vegetative material.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Verhaeghe2016,
title = {Converting bulk sugars into prebiotics: Semi-rational design of a transglucosylase with controlled selectivity},
author = {Tom Verhaeghe and Karel {De Winter} and Magali Berland and Rob {De Vreese} and Matthias D'Hooghe and Bernard Offmann and Tom Desmet},
doi = {10.1039/c5cc09940d},
issn = {1364548X},
year  = {2016},
date = {2016-01-01},
journal = {Chemical Communications},
volume = {52},
number = {18},
pages = {3687--3689},
publisher = {Royal Society of Chemistry},
abstract = {Despite the growing importance of prebiotics in nutrition and gastroenterology, their structural variety is currently still very limited. The lack of straightforward procedures to gain new products in sufficient amounts often hampers application testing and further development. Although the enzyme sucrose phosphorylase can be used to produce the rare disaccharide kojibiose (α-1,2-glucobiose) from the bulk sugars sucrose and glucose, the target compound is only a side product that is difficult to isolate. Accordingly, for this biocatalyst to become economically attractive, the formation of other glucobioses should be avoided and therefore we applied semi-rational mutagenesis and low-throughput screening, which resulted in a double mutant (L341I-Q345S) with a selectivity of 95% for kojibiose. That way, an efficient and scalable production process with a yield of 74% could be established, and with a simple yeast treatment and crystallization step over a hundred grams of highly pure kojibiose (textgreater99.5%) was obtained.},
keywords = {team 1},
pubstate = {published},
tppubtype = {article}
}
@article{avEQ5:DELAVAT:2016aab,
title = {Highly variable individual donor cell fates characterize robust horizontal gene transfer of an integrative and conjugative element},
author = {François Delavat and Sara Mitri and Serge Pelet and Jan Roelof van der Meer},
doi = {10.1073/pnas.1604479113},
year  = {2016},
date = {2016-01-01},
journal = {Proc Natl Acad Sci U S A},
volume = {113},
number = {24},
pages = {E3375-83},
abstract = {Horizontal gene transfer is an important evolutionary mechanism for bacterial adaptation. However, given the typical low transfer frequencies in a bacterial population, little is known about the fate and interplay of donor cells and the mobilized DNA during transfer. Here we study transfer of an integrative and conjugative element (ICE) among individual live bacterial cells. ICEs are widely distributed mobile DNA elements that are different than plasmids because they reside silent in the host chromosome and are maintained through vertical descent. Occasionally, ICEs become active, excise, and transmit their DNA to a new recipient, where it is reintegrated. We develop a fluorescent tool to differentiate excision, transfer, and reintegration of a model ICE named ICEclc (for carrying the clc genes for chlorocatechol metabolism) among single Pseudomonas cells by using time-lapse microscopy. We find that ICEclc activation is initiated in stationary phase cells, but excision and transfer predominantly occur only when such cells have been presented with new nutrients. Donors with activated ICE develop a number of different states, characterized by reduced cell division rates or growth arrest, persistence, or lysis, concomitant with ICE excision, and likely, ICE loss or replication. The donor cell state transitions can be described by using a stochastic model, which predicts that ICE fitness is optimal at low initiation rates in stationary phase. Despite highly variable donor cell fates, ICE transfer is remarkably robust overall, with 75% success after excision. Our results help to better understand ICE behavior and shed a new light on bacterial cellular differentiation during horizontal gene transfer.},
keywords = {bacterial evolution, conjugation, modeling, out_lab, Pseudomonas, time-lapse microscopy},
pubstate = {published},
tppubtype = {article}
}
@article{EQ5:Groisillier:2016,
title = {Determination of Recombinant Mannitol-1-phosphate Dehydrogenase Activity from Ectocarpus sp.},
author = {Agnès Groisillier and Thierry Tonon},
url = {https://doi.org/10.21769/bioprotoc.1982},
doi = {10.21769/bioprotoc.1982},
year  = {2016},
date = {2016-01-01},
journal = {BIO-PROTOCOL},
volume = {6},
number = {21},
publisher = {Bio-Protocol, LLC},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{EQ5:Groisillier:2016b,
title = {Determination of Recombinant Mannitol-1-phosphatase Activity from Ectocarpus sp.},
author = {Agnès Groisillier and Thierry Tonon},
url = {https://doi.org/10.21769%2Fbioprotoc.1896},
doi = {10.21769/bioprotoc.1896},
year  = {2016},
date = {2016-01-01},
journal = {BIO-PROTOCOL},
volume = {6},
number = {16},
publisher = {Bio-Protocol, LLC},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@phdthesis{goux2015fonctionnalisation,
title = {Fonctionnalisation de protéines alternatives aux anticorps appliquée à límagerie médicale en oncologie},
author = {Marine Goux},
url = {https://www.theses.fr/2015NANT2040},
year  = {2015},
date = {2015-12-04},
school = {Université de Nantes},
abstract = {La tomographie par émission de positon (TEP) est une technique d’imagerie médicale permettant le diagnostic et le suivi de patient en oncologie. L’utilisation des anticorps et de leurs fragments pour le ciblage de biomarqueurs en TEP présente de nombreuses difficultés liées notamment à leur clairance lente (taille &gt;100 kDa). Leur marquage, faisant intervenir principalement des réactions peu spécifiques, conduit à un mélange hétérogène de produits et parfois à l’inactivation des protéines. Le développement d’un nouvel outil de suivi in vivo des patients à l’aide de petites protéines alternatives aux anticorps, les Nanofitines (NF), permet de s’affranchir des contraintes liées à la taille (NF ≈ 10 kDa). La mise en place d’une stratégie de marquage originale et site-spécifique d’une NF sans étape de couplage chimique a d’abord été envisagée dans cette étude. L’approche est basée sur la capacité naturelle des phosphates à fixer des cations métalliques. L’insertion génétique d’une étiquette peptidique phosphorylable, in vivo ou in vitro, a permis la chélation d’un lanthanide en solution, le Tb(III), avec une affinité de l’ordre du μM. La seconde génération d’étiquettes peptidiques obtenues par mutagenèse a permis la chélation du Tb(III) avec une affinité d’environ 500 nM à pH7 et 50 nM à pH5,5, et une affinité pour le Ga(III) de l’ordre du μM à pH5,5. Parallèlement, la biodistribution et le ciblage spécifique in vivo d’une NF anti-EGFR radiomarquée à l’aide du 18F-FBEM ont été évalués dans un double modèle tumoral murin. Les images TEP obtenues avec un bon contraste ont permis de valider la preuve de concept quant à l’utilisation des NF en tant qu’outil en imagerie médicale.},
keywords = {team 2, thesis},
pubstate = {published},
tppubtype = {phdthesis}
}
@article{Martin-Jezequel2015,
title = {Effects of organic and inorganic nitrogen on the growth and production of domoic acid by pseudo-nitzschia multiseries and p. Australis (bacillariophyceae) in culture},
author = {Véronique Martin-Jézéquel and Guillaume Calu and Leo Candela and Zouher Amzil and Thierry Jauffrais and Véronique Séchet and Pierre Weigel},
doi = {10.3390/md13127055},
issn = {16603397},
year  = {2015},
date = {2015-12-01},
journal = {Marine Drugs},
volume = {13},
number = {12},
pages = {7067--7086},
publisher = {MDPI AG},
abstract = {Over the last century, human activities have altered the global nitrogen cycle, and anthropogenic inputs of both inorganic and organic nitrogen species have increased around the world, causing significant changes to the functioning of aquatic ecosystems. The increasing frequency of Pseudo-nitzschia spp. in estuarine and coastal waters reinforces the need to understand better the environmental control of its growth and domoic acid (DA) production. Here, we document Pseudo-nitzschia spp. growth and toxicity on a large set of inorganic and organic nitrogen (nitrate, ammonium, urea, glutamate, glutamine, arginine and taurine). Our study focused on two species isolated from European coastal waters: P. multiseries CCL70 and P. australis PNC1. The nitrogen sources induced broad differences between the two species with respect to growth rate, biomass and cellular DA, but no specific variation could be attributed to any of the inorganic or organic nitrogen substrates. Enrichment with ammonium resulted in an enhanced growth rate and cell yield, whereas glutamate did not support the growth of P. multiseries. Arginine, glutamine and taurine enabled good growth of P. australis, but without toxin production. The highest DA content was produced when P. multiseries grew with urea and P. australis grew with glutamate. For both species, growth rate was not correlated with DA content but more toxin was produced when the nitrogen source could not sustain a high biomass. A significant negative correlation was found between cell biomass and DA content in P. australis. This study shows that Pseudo-nitzschia can readily utilize organic nitrogen in the form of amino acids, and confirms that both inorganic and organic nitrogen affect growth and DA production. Our results contribute to our understanding of the ecophysiology of Pseudo-nitzschia spp. and may help to predict toxic events in the natural environment.},
keywords = {Amino acids, Domoic acid, Nitrogen, Pseudo-nitzschia, team 2, Toxic diatoms},
pubstate = {published},
tppubtype = {article}
}
@phdthesis{alligand2015etude,
title = {Étude du rôle des phosphorylations de Rad51 en Y54 et en Y315 sur son fonctionnement},
author = {Brendan Alligand},
url = {https://www.theses.fr/2015NANT2033},
year  = {2015},
date = {2015-11-26},
school = {Université de Nantes},
abstract = {La Recombinaison Homologue (RH) permet la réparation des dommages à l’ADN les plus délétères : les Cassures double brin. L’étape centrale de la RH est basée sur l’activité d’échange de brins de RAD51. Ainsi, l’activité de RAD51 est cruciale pour le maintien de l’intégrité génomique. Toutefois, cette protéine possède également un côté sombre. En effet, la surexpression de RAD51 permet aux cellules cancéreuses de résister aux traitements. Ce qui en fait une cible thérapeutique potentielle pour sensibiliser les cellules cancéreuses au traitement. Une meilleure compréhension du contrôle de l’activité de RAD51 aiderait sûrement à développer des stratégies thérapeutiques. L’activité de RAD51 est régulée par des phosphorylations et plusieurs kinases sont connues pour cibler RAD51. C’est le cas de la kinase c-Abl qui phosphoryle les tyrosines Y54 et Y315 en réponse aux dommages à l’ADN. Mais le rôle de ces phosphorylations est peu connu. C’est pourquoi nous nous sommes intéressés à l’effet de ces phosphorylations sur RAD51. Dans ce but, nous avons produit des mutants de RAD51 mimant la phosphorylation. Leur activité a été analysée et comparée in vitro. Nous avons démontré que le mutant équivalent à une double phosphorylation est incapable de réaliser l’échange de brins. Un défaut de polymérisation de RAD51 serait à l’origine de cette inhibition. Par la suite, la régulation a été étudiée dans le contexte cellulaire. Les résultats préliminaires montrent un effet de la double phosphorylation sur la localisation cellulaire de RAD51. L’inactivation de RAD51 par cette double phosphorylation pourrait participer à la régulation de la voie de la Recombinaison Homologue et serait une étape clef dans la compréhension de la réponse aux dommages à l’ADN.},
keywords = {team 3, thesis},
pubstate = {published},
tppubtype = {phdthesis}
}
@misc{sanejouand2015simple,
title = {A simple Hubble-like law in lieu of dark energy},
author = {Yves-Henri Sanejouand},
url = {https://arxiv.org/abs/1401.2919},
year  = {2015},
date = {2015-11-11},
abstract = {Within the frame of the Λ cold dark matter paradigm, a dark energy component of unknown origin is expected to represent nearly 70% of the energy of the Universe. Herein, a non-standard form of the Hubble law is advocated, with the aim of providing safe grounds on which alternative cosmologies could be developed. Noteworthy, it yields an age-redshift relationship which is consistent with available data. Together with a straightforward analysis of gamma-ray burst counts, it further suggests that the observable Universe has been euclidean and static over the last 12 Gyr. Although a non-standard distance-duality relation is then required for interpreting luminosity distances, the magnitude-redshift relationship obtained is compatible with type Ia supernovae data.},
howpublished = {arXiv:1401.2919},
keywords = {out_lab},
pubstate = {published},
tppubtype = {misc}
}
@article{EQ5:Groisillier:2015c,
title = {Molecular and biochemical characterization of mannitol-1-phosphate dehydrogenase from the model brown alga Ectocarpus sp},
author = {Patricia Bonin and Agnès Groisillier and Alice Raimbault and Anaïs Guibert and Catherine Boyen and Thierry Tonon},
doi = {10.1016/j.phytochem.2015.07.015},
year  = {2015},
date = {2015-09-01},
journal = {Phytochemistry},
volume = {117},
pages = {509-520},
abstract = {The sugar alcohol mannitol is important in the food, pharmaceutical, medical and chemical industries. It is one of the most commonly occurring polyols in nature, with the exception of Archaea and animals. It has a range of physiological roles, including as carbon storage, compatible solute, and osmolyte. Mannitol is present in large amounts in brown algae, where its synthesis involved two steps: a mannitol-1-phosphate dehydrogenase (M1PDH) catalyzes a reversible reaction between fructose-6-phosphate (F6P) and mannitol-1-phosphate (M1P) (EC 1.1.1.17), and a mannitol-1-phosphatase hydrolyzes M1P to mannitol (EC 3.1.3.22). Analysis of the model brown alga Ectocarpus sp. genome provided three candidate genes for M1PDH activities. We report here the sequence analysis of Ectocarpus M1PDHs (EsM1PDHs), and the biochemical characterization of the recombinant catalytic domain of EsM1PDH1 (EsM1PDH1cat). Ectocarpus M1PDHs are representatives of a new type of modular M1PDHs among the polyol-specific long-chain dehydrogenases/reductases (PSLDRs). The N-terminal domain of EsM1PDH1 was not necessary for enzymatic activity. Determination of kinetic parameters indicated that EsM1PDH1cat displayed higher catalytic efficiency for F6P reduction compared to M1P oxidation. Both activities were influenced by NaCl concentration and inhibited by the thioreactive compound pHMB. These observations were completed by measurement of endogenous M1PDH activity and of EsM1PDH gene expression during one diurnal cycle. No significant changes in enzyme activity were monitored between day and night, although transcription of two out of three genes was altered, suggesting different levels of regulation for this key metabolic pathway in brown algal physiology.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid26408012,
title = {OLIGOPELVIS - GETUG P07: a multicentre phase II trial of combined salvage radiotherapy and hormone therapy in oligometastatic pelvic node relapses of prostate cancer},
author = {Stephane Supiot and Emmanuel Rio and Valérie Pacteau and Marie-Hélène Mauboussin and Loïc Campion and François Pein},
doi = {10.1186/s12885-015-1579-0},
issn = {1471-2407},
year  = {2015},
date = {2015-09-01},
urldate = {2015-09-01},
journal = {BMC Cancer},
volume = {15},
pages = {646},
abstract = {BACKGROUND: Metastatic prostate cancer remains a common cause of death in Europe, and improvements in management of the disease are urgently needed. The advent of positron-emission tomography (PET) imaging enhanced with fluorocholine has led to the identification of a new sub-group of metastatic prostate cancer patients: those with so-called oligometastatic disease. Presenting with a low burden of metastatic disease (≤5 lesions), this new sub-group lies between true metastatic prostate cancer patients for whom androgen- deprivation therapy (ADT) is the mainstay of treatment, and patients with a rising PSA, but no visible lesion on conventional imaging, in whom intermittent ADT has been shown to be no less effective than continuous ADT. One might conclude that intermittent ADT would also be the standard of care for oligometastatic prostate cancer patients, but radical strategies such as extensive lymphadenectomy or high-dose radiotherapy have been suggested as another means to delay the need for ADT, and increase its effectiveness once initiated. This study will explore the role of salvage pelvic image-guided intensity-modulated radiation therapy (IMRT) combined with ADT administered for 6 months in pelvic oligometastatic patients in prolonging the failure-free interval between two consecutive ADT courses, or even to cure selected patients with limited metastatic burden.

METHODS/DESIGN: We plan to assess the two year outcome in oligometastatic prostate cancer patients (1-5 pelvic oligometastases) treated concomitantly with high-dose IMRT (54 Gy, 30 fractions to the pelvis and 66 Gy, 30 fractions to the lymph nodes) and ADT for six months.

DISCUSSION: This multicenter prospective phase II study will yield new data regarding the safety and efficacy of high-dose radiotherapy combined with ADT and will provide a basis for a larger phase III study to examine the role of radiotherapy in this population currently treated only with hormone therapy.

TRIAL REGISTRATION: NCT02274779 , date of registration: 23/10/14.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{rEQ4:THIRIET:2015,
title = {Nucleosome Dancing at the Tempo of Histone Tail Acetylation},
author = {Angélique Galvani and Christophe Thiriet},
url = {https://doi.org/10.3390/genes6030607},
doi = {10.3390/genes6030607},
year  = {2015},
date = {2015-07-01},
urldate = {2015-07-01},
journal = {Genes (Basel)},
volume = {6},
number = {3},
pages = {607-21},
abstract = {The impact of histone acetylation on transcription was revealed over 50 years ago by Allfrey and colleagues. However, it took decades for an understanding of the fine mechanism by which this posttranslational modification affects chromatin structure and promotes transcription. Here, we review breakthroughs linking histone tail acetylation, histone dynamics, and transcription. We also discuss the histone exchange during transcription and highlight the important function of a pool of non-chromatinized histones in chromatin dynamics.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{avEQ5:Bailleul_TIRICHINE:2015,
title = {Energetic coupling between plastids and mitochondria drives CO2 assimilation in diatoms},
author = {Benjamin Bailleul and Nicolas Berne and Omer Murik and Dimitris Petroutsos and Judit Prihoda and Atsuko Tanaka and Valeria Villanova and Richard Bligny and Serena Flori and Denis Falconet and Anja Krieger-Liszkay and Stefano Santabarbara and Fabrice Rappaport and Pierre Joliot and Leila Tirichine and Paul G Falkowski and Pierre Cardol and Chris Bowler and Giovanni Finazzi},
url = {https://doi.org/10.1038%2Fnature14599},
doi = {10.1038/nature14599},
year  = {2015},
date = {2015-07-01},
journal = {Nature},
volume = {524},
number = {7565},
pages = {366--369},
publisher = {Springer Science and Business Media LLC},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
@article{avEQ5:Veluchamy_TIRICHINE:2015,
title = {An integrative analysis of post-translational histone modifications in the marine diatom Phaeodactylum tricornutum,},
author = {Alaguraj Veluchamy and Achal Rastogi and Xin Lin and Bérangère Lombard and Omer Murik and Yann Thomas and Florent Dingli and Maximo Rivarola and Sandra Ott and Xinyue Liu and Yezhou Sun and Pablo D Rabinowicz and James McCarthy and Andrew E Allen and Damarys Loew and Chris Bowler and Leila Tirichine},
url = {https://doi.org/10.1186%2Fs13059-015-0671-8},
doi = {10.1186/s13059-015-0671-8},
year  = {2015},
date = {2015-05-01},
journal = {Genome Biology},
volume = {16},
number = {1},
publisher = {Springer Science and Business Media LLC},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{avEQ5:MORISSEY_TIRICHINE:2015,
title = {A Novel Protein, Ubiquitous in Marine Phytoplankton, Concentrates Iron at the Cell Surface and Facilitates Uptake},
author = {Joe Morrissey and Robert Sutak and Javier Paz-Yepes and Atsuko Tanaka and Ahmed Moustafa and Alaguraj Veluchamy and Yann Thomas and Hugo Botebol and François-Yves Bouget and Jeffrey~B. McQuaid and Leila Tirichine and Andrew~E. Allen and Emmanuel Lesuisse and Chris Bowler},
url = {https://doi.org/10.1016%2Fj.cub.2014.12.004},
doi = {10.1016/j.cub.2014.12.004},
year  = {2015},
date = {2015-02-01},
journal = {Current Biology},
volume = {25},
number = {3},
pages = {364--371},
publisher = {Elsevier BV},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid26442216,
title = {Preclinical Evaluation of Intraoperative Low-Energy Photon Radiotherapy Using Spherical Applicators in Locally Advanced Prostate Cancer},
author = {François Buge and Sophie Chiavassa and Chloé Hervé and Jérôme Rigaud and Grégory Delpon and Stéphane Supiot},
doi = {10.3389/fonc.2015.00204},
issn = {2234-943X},
year  = {2015},
date = {2015-01-01},
urldate = {2015-01-01},
journal = {Front Oncol},
volume = {5},
pages = {204},
abstract = {BACKGROUND: Surgery plus adjuvant radiotherapy is standard care for locally advanced prostate cancer (stage pT3R1). Intraoperative low-energy photon radiotherapy offers several advantages over external beam radiotherapy, and several systems are now available for its delivery, using spherical applicators, which require only limited shielding. The aim of this study was to evaluate the feasibility of this technique for the prostate bed.

MATERIALS AND METHODS: Applicators were assessed using MRI image data and cadaveric dissection. In cadavers, targeted tissues, defined as a urethral section, both neurovascular bundle sections, the bladder neck and the beds of the seminal vesicles, were marked with metallic surgical clips. Distances between clips and applicator were measured using CT. A dosimetric study of the application of 12 Gy at 5 mm depth was performed using CT images of prostatectomized cadavers.

RESULTS: Using MRI images from 34 prostate cancer patients, we showed that the ideal applicator diameter ranges from 45 to 70 mm. Using applicators of different sizes to encompass the prostate bed in nine cadavers, we showed that the distance between target tissues and applicator was &lt;2 mm for all target tissues except the upper extremity of the seminal vesicles (19 mm). Dosimetric study showed a good dose distribution in all target tissues in contact with the applicator, with a low probability of rectum and bladder complication.

CONCLUSION: Intraoperative radiotherapy of the prostate bed is feasible, with good coverage of targeted tissues. Clinical study of safety and efficacy is now required.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid26528437,
title = {Integrating Geriatric Assessment into Decision-Making after Prostatectomy: Adjuvant Radiotherapy, Salvage Radiotherapy, or None?},
author = {Aurore Goineau and Bénédicte d'Aillières and Laure de Decker and Stéphane Supiot},
doi = {10.3389/fonc.2015.00227},
issn = {2234-943X},
year  = {2015},
date = {2015-01-01},
urldate = {2015-01-01},
journal = {Front Oncol},
volume = {5},
pages = {227},
abstract = {Despite current advancements in the field, management of older prostate cancer patients still remains a big challenge for Geriatric Oncology. The International Society of Geriatric Oncology (ISGO) has recently updated its recommendations in this area, and these have been widely adopted, notably by the European Association of Urology. This article outlines the principles that should be observed in the management of elderly patients who have recently undergone prostatectomy for malignancy or with a biochemical relapse following prostatectomy. Further therapeutic intervention should not be considered in those patients who are classified as frail in the geriatric assessment. In patients presenting better health conditions, salvage radiotherapy is to be preferred to adjuvant radiotherapy, which is only indicated in certain exceptional cases. Radiotherapy of the operative bed presents a higher risk to the elderly. Additionally, hormone therapy clearly shows higher side effects in older patients and therefore it should not be administered to asymptomatic patients. We propose a decision tree based on the ISGO recommendations, with specific modifications for patients in biochemical relapse. },
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{PICHON2015S82,
title = {Impact of Functional and/or Phenotypic PET Imaging on the Determination of Clinical Target Volumes of Vertebral Metastases Before Stereotactic Body Radiation Therapy Compared to MRI},
author = {B Pichon and S Supiot and G Delpon and L Ferrer and A Rauscher and M Leturnier and V Libois and A Goineau and A Faivre Chauvet and P Baumgartner and DM Goldenberg and R Sharkey and J Barbet and F Kraeber-Bodere and M Mahe and C Rousseau},
url = {https://www.sciencedirect.com/science/article/pii/S0360301615009293},
doi = {https://doi.org/10.1016/j.ijrobp.2015.07.198},
issn = {0360-3016},
year  = {2015},
date = {2015-01-01},
urldate = {2015-01-01},
journal = {International Journal of Radiation Oncology*Biology*Physics},
volume = {93},
number = {3, Supplement},
pages = {S82-S83},
note = {Proceedings of the American Society for Radiation Oncology 57th Annual Meeting},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{PICHON2015E83,
title = {High Dose Hypofractionated Stereotactic Body Radiation Therapy of Non Compressive Vertebral Bone Metastases in Combination With Zoledronic Acid: A Phase 1 Study},
author = {B Pichon and MA Mahe and G Delpon and F Thillays and C Carrie and P Cellier and P Pommier and C Laude and A Mervoyer and S Supiot},
url = {https://www.sciencedirect.com/science/article/pii/S036030161501487X},
doi = {https://doi.org/10.1016/j.ijrobp.2015.07.756},
issn = {0360-3016},
year  = {2015},
date = {2015-01-01},
urldate = {2015-01-01},
journal = {International Journal of Radiation Oncology*Biology*Physics},
volume = {93},
number = {3, Supplement},
pages = {E83},
note = {Proceedings of the American Society for Radiation Oncology 57th Annual Meeting},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{HENNEQUIN2015S44,
title = {Randomized Phase 3 Trial of Dose Escalation (80 vs 70 Gy) in High-Risk Prostate Cancers Combined With Long-term Androgen Deprivation: GETUG-AFU 18 Trial, Acute and 1-Year Toxicities},
author = {C Hennequin and PM Richaud and L Roca and M Silva and I Latorzeff and V Beckendorff and C Carrie and A Benyoucef and A Hasbini and S Supiot and P Ronchin and T Wachter and D Azria and PE Cailleux and L Cormier and M Habibian and G Delaroche},
url = {https://www.sciencedirect.com/science/article/pii/S036030161500838X},
doi = {https://doi.org/10.1016/j.ijrobp.2015.07.107},
issn = {0360-3016},
year  = {2015},
date = {2015-01-01},
urldate = {2015-01-01},
journal = {International Journal of Radiation Oncology*Biology*Physics},
volume = {93},
number = {3, Supplement},
pages = {S44-S45},
note = {Proceedings of the American Society for Radiation Oncology 57th Annual Meeting},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@inbook{EQ1:SANEJOUAND:2015,
title = {Simplified flexibility analysis of proteins},
author = {Yves-Henri Sanejouand},
editor = {Monika Fuxreiter},
url = {http://arxiv.org/abs/1312.5639},
year  = {2015},
date = {2015-01-01},
booktitle = {Computational Approaches to Protein Dynamics: From Quantum to Coarse-Grained Methods},
pages = {153--182},
publisher = {CRC Press},
chapter = {5},
abstract = {A simple way to get insights about the possible functional motions of a protein is to perform a normal mode analysis (NMA). Indeed, it has been shown that low-frequency modes thus obtained are often closely related to domain motions involved in protein function. Moreover, because protein low-frequency modes are known to be robust, NMA can be performed using coarse-grained models. As a consequence, it can be done for large ensembles of conformations as well as for large systems, like the ribosome, whole virus capsids, etc. Unexpectedly, on the high-frequency side, modes obtained with cutoff-based coarse-grained models also seem able to provide useful insights on protein dynamical properties.},
keywords = {team 1},
pubstate = {published},
tppubtype = {inbook}
}
@article{biom5043204,
title = {DNA Damage Signalling and Repair Inhibitors: The Long-Sought-After Achilles’ Heel of Cancer},
author = {Denis Velic and Anthony M Couturier and Maria Tedim Ferreira and Amélie Rodrigue and Guy G Poirier and Fabrice Fleury and Jean-Yves Masson},
url = {https://www.mdpi.com/2218-273X/5/4/3204},
doi = {10.3390/biom5043204},
issn = {2218-273X},
year  = {2015},
date = {2015-01-01},
journal = {Biomolecules},
volume = {5},
number = {4},
pages = {3204--3259},
abstract = {For decades, radiotherapy and chemotherapy were the two only approaches exploiting DNA repair processes to fight against cancer. Nowadays, cancer therapeutics can be a major challenge when it comes to seeking personalized targeted medicine that is both effective and selective to the malignancy. Over the last decade, the discovery of new targeted therapies against DNA damage signalling and repair has offered the possibility of therapeutic improvements in oncology. In this review, we summarize the current knowledge of DNA damage signalling and repair inhibitors, their molecular and cellular effects, and future therapeutic use.},
keywords = {team 3, thesis},
pubstate = {published},
tppubtype = {article}
}
@article{CESCHIN201523947,
title = {Disruption of Nucleotide Homeostasis by the Antiproliferative Drug 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside Monophosphate (AICAR)*},
author = {Johanna Ceschin and Hans Caspar Hürlimann and Christelle Saint-Marc and Delphine Albrecht and Typhaine Violo and Michel Moenner and Bertrand Daignan-Fornier and Benoît Pinson},
url = {https://www.sciencedirect.com/science/article/pii/S0021925820447301},
doi = {https://doi.org/10.1074/jbc.M115.656017},
issn = {0021-9258},
year  = {2015},
date = {2015-01-01},
journal = {Journal of Biological Chemistry},
volume = {290},
number = {39},
pages = {23947-23959},
abstract = {5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside monophosphate (AICAR) is a natural metabolite with potent anti-proliferative and low energy mimetic properties. At high concentration, AICAR is toxic for yeast and mammalian cells, but the molecular basis of this toxicity is poorly understood. Here, we report the identification of yeast purine salvage pathway mutants that are synthetically lethal with AICAR accumulation. Genetic suppression revealed that this synthetic lethality is in part due to low expression of adenine phosphoribosyl transferase under high AICAR conditions. In addition, metabolite profiling points to the AICAR/NTP balance as crucial for optimal utilization of glucose as a carbon source. Indeed, we found that AICAR toxicity in yeast and human cells is alleviated when glucose is replaced by an alternative carbon source. Together, our metabolic analyses unveil the AICAR/NTP balance as a major factor of AICAR antiproliferative effects.},
keywords = {nucleoside/nucleotide analog, nucleoside/nucleotide metabolism, out_lab, purine, yeast genetics, yeast metabolism},
pubstate = {published},
tppubtype = {article}
}
@article{chandola2015role,
title = {Role of the N6-methyladenosine RNA mark in gene regulation and its implications on development and disease},
author = {Udita Chandola and Radhika Das and Binay Panda},
doi = {https://doi.org/10.1093/bfgp/elu039},
year  = {2015},
date = {2015-01-01},
journal = {Briefings in functional genomics},
volume = {14},
number = {3},
pages = {169--179},
publisher = {Oxford University Press},
abstract = {Epigenetics is a field that encompasses chemical modifications of DNA and histone proteins, both of which alter gene expression without changing the underlying nucleotide sequence. DNA methylation and modifications of histone tails have been studied in detail and are now known to be global gene regulatory mechanisms. An analogous post-transcriptional modification is chemical modification of specific nucleotides in RNA. Study of RNA modifications is a nascent field as yet, and the significance of these marks in controlling cell growth and differentiation is just beginning to be appreciated. The addition of a methyl group to adenosine (N-methyl-6-adenosine) or m6A is the most abundant modification in mammalian mRNAs. Though identified four decades ago, interest in this particular modification was set off by the discovery that the obesity gene FTO was an RNA demethylase. Since then, many studies have investigated m6A modification in different species. In this review, we summarize the current literature and hypotheses about the presence and function of this ubiquitous RNA modification in mammals, viruses, yeast and plants in terms of the consensus sequence and the methyltransferase/demethylation machinery identified thus far. We discuss its potential role in regulating molecular and physiological processes in each of these organisms, especially its role in RNA splicing, RNA degradation and development. We also enlist the methodologies developed so far, both locus-specific and transcriptome-wide, to study this modification. Lastly, we discuss whether m6A alterations have consequences on modulating disease aetiology, and speculate about its potential role in cancer.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{nair2015gene,
title = {Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx},
author = {Jayalakshmi Nair and Prachi Jain and Udita Chandola and Vinayak Palve and Harsha N R Vardhan and Ram Bhupal Reddy and Vikram D Kekatpure and Amritha Suresh and Moni Abraham Kuriakose and Binay Panda},
doi = {10.18632/genesandcancer.69},
year  = {2015},
date = {2015-01-01},
journal = {Genes & cancer},
volume = {6},
number = {7-8},
pages = {328},
publisher = {Impact Journals, LLC},
abstract = {Laryngo-pharyngeal squamous cell carcinomas are one of the most common head and neck cancers. Despite the presence of a large body of information, molecular biomarkers are not currently used in the diagnosis, treatment and management of patients for this group of cancer. Here, we have profiled expression of genes and microRNAs of larynx and hypopharynx tumors using high-throughput sequencing experiments. We found that matrix metalloproteinases along with SCEL, CRNN, KRT4, SPINK5, and TGM3 among others have significantly altered expression in these tumors. Alongside gene expression, the microRNAs hsa-miR-139, hsa-miR-203 and the hsa-miR-424/503 cluster have aberrant expression in these cancers. Using target genes for these microRNAs, we found the involvement of pathways linked to cell cycle, p53 signaling, and viral carcinogenesis significant (P-values 10−13, 10−9 and 10−7 respectively). Finally, using an ensemble machine-learning tool, we discovered a unique 8-gene signature for this group of cancers that differentiates the group from the other tumor subsites of head and neck region. We investigated the role of promoter methylation in one of these genes, WIF1, and found no correlation between DNA methylation and down-regulation of WIF1. We validated our findings of gene expression, 8-gene signature and promoter methylation using q-PCR, data from TCGA and q-MSP respectively. 
 Data presented in this manuscript has been submitted to the NCBI Geo database with the accession number GSE67994.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Segaliny2015,
title = {IL-34 and M-CSF form a novel heteromeric cytokine and regulate the M-CSF receptor activation and localization},
author = {Aude I Ségaliny and Régis Brion and Bénédicte Brulin and Mike Maillasson and Céline Charrier and Stéphane Téletchéa and Dominique Heymann},
doi = {10.1016/j.cyto.2015.05.029},
issn = {10960023},
year  = {2015},
date = {2015-01-01},
journal = {Cytokine},
volume = {76},
number = {2},
pages = {170--181},
abstract = {Interleukin-34 (IL-34) is a newly-discovered homodimeric cytokine that regulates, like Macrophage Colony-Stimulating Factor (M-CSF), the differentiation of the myeloid lineage through M-CSF receptor (M-CSFR) signaling pathways. To date, both cytokines have been considered as competitive cytokines with regard to the M-CSFR. The aim of the present work was to study the functional relationships of these cytokines on cells expressing the M-CSFR. We demonstrate that simultaneous addition of M-CSF and IL-34 led to a specific activation pattern on the M-CSFR, with higher phosphorylation of the tyrosine residues at low concentrations. Similarly, both cytokines showed an additive effect on cellular proliferation or viability. In addition, BIAcore experiments demonstrated that M-CSF binds to IL-34, and molecular docking studies predicted the formation of a heteromeric M-CSF/IL-34 cytokine. A proximity ligation assay confirmed this interaction between the cytokines. Finally, co-expression of the M-CSFR and its ligands differentially regulated M-CSFR trafficking into the cell. This study establishes a new foundation for the understanding of the functional relationship between IL-34 and M-CSF, and gives a new vision for the development of therapeutic approaches targeting the IL-34/M-CSF/M-CSFR axis.},
keywords = {CFMS trafficking, Heteromeric cytokine, Interleukin-34, Macrophage-Colony Stimulating Factor, Molecular modeling, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{Faucon2015,
title = {Are Fluorescent Organic Nanoparticles Relevant Tools for Tracking Cancer Cells or Macrophages?},
author = {Adrien Faucon and Houda Benhelli-Mokrani and Luis A w Córdova and Bénédicte Brulin and Dominique Heymann and Philippe Hulin and Steven Nedellec and Eléna Ishow},
doi = {10.1002/adhm.201500562},
issn = {21922659},
year  = {2015},
date = {2015-01-01},
journal = {Advanced Healthcare Materials},
volume = {4},
number = {17},
pages = {2727--2734},
abstract = {Strongly solvatochromic fluorophores are devised, containing alkyl chains and enable to self-assemble as very bright fluorescent organic nanoparticles (FONs) in water (φf = 0.28). The alkyl chains impart each fluorophore with strongly hydrophobic surroundings, causing distinct emission colors between FONs where the fluorophores are associated, and their disassembled state. Such color change is harnessed to assess the long-term fate of FONs in both cancer cells and monocytes/macrophages. Disintegration of the orange-emitting FONs by monocytes/macrophages is evidenced through the formation of micrometer green-yellowish emitting vesicles. By contrast, cancer cells retain longer the integrity of organic nanoparticles. In both cases, no significant toxicity is detected, making FONs as valuable bioimaging agents for cell tracking with weak risks of deleterious accumulation and low degradation rate. Long-term fate of fluorescent organic nanoparticles (FONs), known as very bright imaging agents and made of self-assembled solvatochromic fluorophores, is explored in both cancer cells and monocytes/macrophages. Disintegration of the orange-emitting FONs by monocytes/macrophages is evidenced through the formation of micrometer green-yellowish emitting vesicles. By contrast, cancer cells retain longer the integrity of organic nanoparticles.},
keywords = {Biodegradation, Bioimaging, Cancer cells, Fluorescent organic nanoparticles, Monocytes/macrophages, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Qi2015,
title = {Nuclear magnetic resonance spectroscopy characterization of interaction of Tau with DNA and its regulation by phosphorylation},
author = {Haoling Qi and François Xavier Cantrelle and Houda Benhelli-Mokrani and Caroline Smet-Nocca and Luc Buée and Guy Lippens and Eliette Bonnefoy and Marie Christine Galas and Isabelle Landrieu},
doi = {10.1021/bi5014613},
issn = {15204995},
year  = {2015},
date = {2015-01-01},
journal = {Biochemistry},
volume = {54},
number = {7},
pages = {1525--1533},
abstract = {The capacity of endogenous Tau to bind DNA has been recently identified in neurons under physiological or oxidative stress conditions. Characterization of the protein domains involved in Tau-DNA complex formation is an essential first step in clarifying the contribution of Tau-DNA interactions to neurological biological processes. To identify the amino acid residues involved in the interaction of Tau with oligonucleotides, we have characterized a Tau-DNA complex using nuclear magnetic resonance spectroscopy. Interaction of an AT-rich or GC-rich 22 bp oligonucleotide with Tau showed multiple points of anchoring along the intrinsically disordered Tau protein. The main sites of contact characterized here correspond to the second half of the proline-rich domain (PRD) of Tau and the R2 repeat in the microtubule binding domain. This latter interaction site includes the PHF6∗ sequence known to govern Tau aggregation. The characterization was pursued by studying the binding of phosphorylated forms of Tau, displaying multiple phosphorylation sites mainly in the PRD, to the same oligonucleotide. No interaction of phospho-Tau with the oligonucleotide was detected, suggesting that pathological Tau phosphorylation could affect the physiological function of Tau mediated by DNA binding.},
keywords = {team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Terentev2015,
title = {Organocatalytic peroxidation of malonates, β-ketoesters, and cyanoacetic esters using n-Bu4NI/t-BuOOH-mediated intermolecular oxidative C(sp3)-O coupling},
author = {Alexander O Terent'ev and Alexander T Zdvizhkov and Dmitri O Levitsky and Fabrice Fleury and Roman A Pototskiy and Alena N Kulakova and Gennady I Nikishin},
url = {http://dx.doi.org/10.1016/j.tet.2015.09.047},
doi = {10.1016/j.tet.2015.09.047},
issn = {14645416},
year  = {2015},
date = {2015-01-01},
journal = {Tetrahedron},
volume = {71},
number = {47},
pages = {8985--8990},
publisher = {Elsevier Ltd},
abstract = {A new organocatalytic approach for the synthesis of peroxides based on CH activation of a sp3-hybridized carbon atom is reported. Peroxides were prepared in 31-89% yield by the reaction of malonates, β-ketoesters, and cyanoacetic esters with a Bu4NI/tert-butyl hydroperoxide system. The formation of the expected hydroxylation products was not observed. In the discovered reaction, tert-butyl hydroperoxide plays a dual role by acting as the oxidant and the O-reagent for the C-O coupling. The synthesis can be scaled up to generate gram quantities of the target products.},
keywords = {Malonates, Organocatalysis, Oxidative coupling, Peroxides, team 3, Tetra-n-butylammonium iodide},
pubstate = {published},
tppubtype = {article}
}
@article{Arab-Jaziri2015,
title = {Enhancing the chemoenzymatic synthesis of arabinosylated xylo-oligosaccharides by GH51 α-l-arabinofuranosidase},
author = {Faten Arab-Jaziri and Bastien Bissaro and Charles Tellier and Michel Dion and Régis Fauré and Michael J O'Donohue},
doi = {10.1016/j.carres.2014.10.029},
issn = {1873426X},
year  = {2015},
date = {2015-01-01},
journal = {Carbohydrate Research},
volume = {401},
pages = {64--72},
publisher = {Elsevier Ltd},
abstract = {Random mutagenesis was performed on the α-l-arabinofuranosidase of Thermobacillus xylanilyticus in order to enhance its ability to perform transarabinofuranosylation using natural xylo-oligosaccharides as acceptors. To achieve this goal, a two-step, high-throughput digital imaging protocol involving a colorimetric substrate was used to screen a library of 30,000 mutants. In the first step this screen selected for hydrolytically-impaired mutants, and in the second step the screen identified mutants whose global activity was improved in the presence of a xylo-oligosaccharide mixture. Thereby, 199 mutants displaying lowered hydrolytic activity and modified properties were detected. In the presence of these xylo-oligosaccharides, most of the 199 (i.e., 70%) enzymes were less inhibited and some (18) mutants displayed an unambiguous alleviation of inhibition (textless25% loss of activity). More precise monitoring of reactions catalyzed by the most promising mutants revealed a significant improvement of the synthesis yields of transglycosylation products (up to 18% compared to 9% for the parental enzyme) when xylobiose was present in the reaction. Genetic analysis of improved mutants revealed that many of the amino acid substitutions that correlate with the modified phenotype are located in the vicinity of the active site, particularly in subsite -1. Consequently, we hypothesize that these mutations modify the active site topology or the molecular interaction network of the l-arabinofuranoside donor substrate, thus impairing the hydrolysis and concomitantly favoring transglycosylation onto natural acceptors.},
keywords = {Glycoside hydrolase, Inhibition, Pentose/furanose, team 2, Transglycosylation, Xylo-oligosaccharide},
pubstate = {published},
tppubtype = {article}
}
@article{Andre-Miral2015,
title = {De novo design of a trans-β-N-acetylglucosaminidase activity from a GH1 β-glycosidase by mechanism engineering},
author = {Corinne André-Miral and Fankroma Mt Koné and Claude Solleux and Cyrille Grandjean and Michel Dion and Vinh Tran and Charles Tellier},
doi = {10.1093/glycob/cwu121},
issn = {14602423},
year  = {2015},
date = {2015-01-01},
journal = {Glycobiology},
volume = {25},
number = {4},
pages = {394--402},
abstract = {Glycoside hydrolases are particularly abundant in all areas of metabolism as they are involved in the degradation of natural polysaccharides and glycoconjugates. These enzymes are classified into 133 families (CAZy server, http://www.cazy.org) in which members of each family have a similar structure and catalytic mechanism. In order to understand better the structure/function relationships of these enzymes and their evolution and to develop new robust evolved glycosidases, we undertook to convert a Family 1 thermostable β-glycosidase into an exo-β-N-acetylglucosaminidase. This latter activity is totally absent in Family 1, while natural β-hexosaminidases belong to CAZy Families 3, 20 and 84. Using molecular modeling, we first showed that the docking of N-acetyl-d-glucosamine in the subsite -1 of the β-glycosidase from Thermus thermophilus (TtβGly) suggested several steric conflicts with active site amino-acids (N163, E338) induced by the N-acetyl group. Both N163A and N163D-E338G mutations induced significant N-acetylglucosaminidase activity in TtβGly. The double mutant N163D-E338G was also active on the bicyclic oxazoline substrate, suggesting that this mutated enzyme uses a catalytic mechanism involving a substrate-assisted catalysis with a noncovalent oxazoline intermediate, similar to the N-acetylglucosaminidases from Families 20 and 84. Furthermore, a very efficient trans-N-acetylglucosaminidase activity was observed when the double mutant was incubated in the presence of NAG-oxazoline as a donor and N-methyl-O-benzyl-N-(β-d-glucopyranosyl)-hydroxylamine as an acceptor. More generally, this work demonstrates that it is possible to exchange the specificities and catalytic mechanisms with minimal changes between phylogenetically distant protein structures.},
keywords = {mechanism engineering, N-acetylglucosaminidase, substrate-assisted catalysis, team 2, transglycosidase, β-glycosidase},
pubstate = {published},
tppubtype = {article}
}
@article{Brissonnet2015,
title = {Polymeric iminosugars improve the activity of carbohydrate-processing enzymes},
author = {Yoan Brissonnet and Simon Ladevèze and David Teze and Emeline Fabre and David Deniaud and Franck Daligault and Charles Tellier and Sergej Šesták and Magali Remaud-Simeon and Gabrielle Potocki-Veronese and Sébastien G Gouin},
doi = {10.1021/acs.bioconjchem.5b00081},
issn = {15204812},
year  = {2015},
date = {2015-01-01},
journal = {Bioconjugate Chemistry},
volume = {26},
number = {4},
pages = {766--772},
abstract = {Multivalent iminosugars have recently emerged as powerful tools to inhibit the activities of specific glycosidases. In this work, biocompatible dextrans were coated with iminosugars to form linear and ramified polymers with unprecedently high valencies (from 20 to 900) to probe the evolution of the multivalent inhibition as a function of ligand valency. This study led to the discovery that polyvalent iminosugars can also significantly enhance, not only inhibit, the enzymatic activity of specific glycoside-hydrolase, as observed on two galactosidases, a fucosidase, and a bacterial mannoside phosphorylase for which an impressive 70-fold activation was even reached. The concept of glycosidase activation is largely unexplored, with a unique recent example of small-molecules activators of a bacterial O-GlcNAc hydrolase. The possibility of using these polymers as "artificial enzyme effectors may therefore open up new perspectives in therapeutics and biocatalysis.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{Advedissian2015,
title = {Les galectines: Des lectines pas comme les autres},
author = {Tamara Advedissian and Frédérique Deshayes and Françoise Poirier and Cyrille Grandjean and Mireille Viguier},
doi = {10.1051/medsci/20153105011},
issn = {19585381},
year  = {2015},
date = {2015-01-01},
journal = {Medecine/Sciences},
volume = {31},
number = {5},
pages = {499--505},
abstract = {Galectins constitute a family of soluble animal lectins defined by their evolutionary conserved carbohydrate recognition domain and their affinity for β-galactosides containing glycoconjugates. Each galectin is characterized by a specific spatio-temporal distribution and a unique set of ligands and molecular partners. Interestingly, galectins are found both extracellularly and intracellularly and modulate various cellular processes. Knock-out mutant mice for galectins-1, 3 or 7 are viable but display a wide range of defects under various stress conditions. Indeed, galectins are multifunctional proteins involved in cell-cell and cell-extracellular matrix interactions, organization of membrane domains, cell signalling and also in intracellular trafficking, apoptosis, regulation of cell cycle. Galectins represent potential therapeutic targets, especially in the context of cancer and inflammatory diseases.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{Cabezas2015,
title = {Leishmania cell wall as a potent target for antiparasitic drugs. A focus on the glycoconjugates},
author = {Yari Cabezas and Laurent Legentil and Florence Robert-Gangneux and Franck Daligault and Sorya Belaz and Caroline Nugier-Chauvin and Sylvain Tranchimand and Charles Tellier and Jean Pierre Gangneux and Vincent Ferri{è}res},
doi = {10.1039/c5ob00563a},
issn = {14770520},
year  = {2015},
date = {2015-01-01},
journal = {Organic and Biomolecular Chemistry},
volume = {13},
number = {31},
pages = {8393--8404},
publisher = {Royal Society of Chemistry},
abstract = {Although leishmaniasis has been studied for over a century, the fight against cutaneous, mucocutaneous and visceral forms of the disease remains a hot topic. This review refers to the parasitic cell wall and more particularly to the constitutive glycoconjugates. The structures of the main glycolipids and glycoproteins, which are species-dependent, are described. The focus is on the disturbance of the lipid membrane by existing drugs and possible new ones, in order to develop future therapeutic agents.},
keywords = {team 2},
pubstate = {published},
tppubtype = {article}
}
@article{RN33,
title = {Knowing the Parasite: Biology and Genetics of Orobanche},
author = {Philippe Delavault},
url = {https://doi.org/10.1515/helia-2014-0030},
doi = {doi:10.1515/helia-2014-0030},
year  = {2015},
date = {2015-01-01},
urldate = {2015-01-01},
journal = {Helia},
volume = {38},
number = {62},
pages = {15-29},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Mahajan2015a,
title = {Use of a structural alphabet to find compatible folds for amino acid sequences},
author = {Swapnil Mahajan and Alexandre G {De Brevern} and Yves-Henri Sanejouand and Narayanaswamy Srinivasan and Bernard Offmann},
doi = {10.1002/pro.2581},
issn = {1469896X},
year  = {2015},
date = {2015-01-01},
journal = {Protein Science},
volume = {24},
number = {1},
pages = {145--153},
abstract = {The structural annotation of proteins with no detectable homologs of known 3D structure identified using sequence-search methods is a major challenge today. We propose an original method that computes the conditional probabilities for the amino-acid sequence of a protein to fit to known protein 3D structures using a structural alphabet, known as "Protein Blocks" (PBs). PBs constitute a library of 16 local structural prototypes that approximate every part of protein backbone structures. It is used to encode 3D protein structures into 1D PB sequences and to capture sequence to structure relationships. Our method relies on amino acid occurrence matrices, one for each PB, to score global and local threading of query amino acid sequences to protein folds encoded into PB sequences. It does not use any information from residue contacts or sequence-search methods or explicit incorporation of hydrophobic effect. The performance of the method was assessed with independent test datasets derived from SCOP 1.75A. With a Z-score cutoff that achieved 95% specificity (i.e., less than 5% false positives), global and local threading showed sensitivity of 64.1% and 34.2%, respectively. We further tested its performance on 57 difficult CASP10 targets that had no known homologs in PDB: 38 compatible templates were identified by our approach and 66% of these hits yielded correctly predicted structures. This method scales-up well and offers promising perspectives for structural annotations at genomic level. It has been implemented in the form of a web-server that is freely available at http://www.bo-protscience.fr/forsa.},
keywords = {fold recognition, protein blocks, protein domains, protein structures, sequence-structure relationship, Structural alphabet, structural annotation, team 1, threading},
pubstate = {published},
tppubtype = {article}
}
@article{RN22,
title = {Seed response to strigolactone is controlled by abscisic acid-independent DNA methylation in the obligate root parasitic plant, Phelipanche ramosa L. Pomel},
author = {Marc-Marie Lechat and Guillaume Brun and Grégory Montiel and Christophe Véronési and Philippe Simier and Séverine Thoiron and Jean-Bernard Pouvreau and Philippe Delavault},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449535/pdf/erv119.pdf},
doi = {10.1093/jxb/erv119},
issn = {0022-0957 (Print) 0022-0957},
year  = {2015},
date = {2015-01-01},
urldate = {2015-01-01},
journal = {J Exp Bot},
volume = {66},
number = {11},
pages = {3129-40},
abstract = {Seed dormancy release of the obligate root parasitic plant, Phelipanche ramosa, requires a minimum 4-day conditioning period followed by stimulation by host-derived germination stimulants, such as strigolactones. Germination is then mediated by germination stimulant-dependent activation of PrCYP707A1, an abscisic acid catabolic gene. The molecular mechanisms occurring during the conditioning period that silence PrCYP707A1 expression and regulate germination stimulant response are almost unknown. Here, global DNA methylation quantification associated with pharmacological approaches and cytosine methylation analysis of the PrCYP707A1 promoter were used to investigate the modulation and possible role of DNA methylation during the conditioning period and in the PrCYP707A1 response to GR24, a synthetic strigolactone analogue. Active global DNA demethylation occurs during the conditioning period and is required for PrCYP707A1 activation by GR24 and for subsequent seed germination. Treatment with 5-azacytidine, a DNA-hypomethylating molecule, reduces the length of the conditioning period. Conversely, hydroxyurea, a hypermethylating agent, inhibits PrCYP707A1 expression and seed germination. Methylated DNA immunoprecipitation followed by PCR experiments and bisulfite sequencing revealed that DNA demethylation particularly impacts a 78-nucleotide sequence in the PrCYP707A1 promoter. The results here demonstrate that the DNA methylation status during the conditioning period plays a crucial role independently of abscisic acid in the regulation of P. ramosa seed germination by controlling the strigolactone-dependent expression of PrCYP707A1.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Mahajan2015b,
title = {On the relationship between low-frequency normal modes and the large-scale conformational changes of proteins},
author = {Swapnil Mahajan and Yves-Henri Sanejouand},
url = {http://dx.doi.org/10.1016/j.abb.2014.12.020},
doi = {10.1016/j.abb.2014.12.020},
issn = {10960384},
year  = {2015},
date = {2015-01-01},
journal = {Archives of Biochemistry and Biophysics},
volume = {567},
pages = {59--65},
publisher = {Elsevier Inc.},
abstract = {Normal mode analysis is a computational technique that allows to study the dynamics of biological macromolecules. It was first applied to small protein cases, more than thirty years ago. The interest in this technique then raised when it was realized that it can provide insights about the large-scale conformational changes a protein can experience, for instance upon ligand binding. As it was also realized that studying highly simplified protein models can provide similar insights, meaning that this kind of analysis can be both quick and simple to handle, several applications were proposed, in the context of various structural biology techniques. This review focuses on these applications, as well as on how the functional relevance of the lowest-frequency modes of proteins was established.},
keywords = {Conformational transition, elastic network model, Flexibility, low-frequency modes, Structure-function relationship, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{RN34,
title = {History of the race structure of Orobanche cumana and the breeding of sunflower for resistance to this parasitic weed: A review},
author = {Leire Molinero-Ruiz and Philippe Delavault and Begoña Pérez-Vich and Maria Pacureanu-Joita and Mariano Bulos and Emiliano Altieri and Juan Domínguez},
url = {https://revistas.inia.es/index.php/sjar/article/view/8080 
https://revistas.inia.es/index.php/sjar/article/download/8080/2588},
doi = {10.5424/sjar/2015134-8080},
year  = {2015},
date = {2015-01-01},
urldate = {2015-01-01},
journal = {Spanish Journal of Agricultural Research},
volume = {13},
number = {4},
pages = {e10R01},
abstract = {Broomrape, caused by Orobanche cumana, has affected sunflowers since the early 20th century in Eastern Europe. Currently, it limits sunflower oil production in Southern and Eastern Europe and in some areas of Asia, causing around 50% seed losses when susceptible hybrids are grown. Covered in this review are aspects such as: biological processes that are common to Orobanche spp. and/or particular to O. cumana in sunflower, genetic resistance and its mechanisms, races of the parasite identified in different countries throughout the time and their increasing virulence, and breeding for resistance to some herbicides as a novel control option. The main purpose is to present an updated and, as far as possible, complete picture of the way both the parasitic weed and its host crop have evolved in time, and how they co-exist in the current agriculture. Additionally, we propose a system for determining the races of the parasite that can be internationally adopted from now. In the context of minimal harmful effects on the environment, changing patterns of land use in farming systems, and global environment changes, the final goal of this work is to provide all those interested in parasites from field crops and their integrated management compiled information on the sunflower – O. cumana system as a case study.},
keywords = {team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Teze2015,
title = {Semi-rational approach for converting a GH36 α-glycosidase into an α-transglycosidase},
author = {David Teze and Franck Daligault and Vincent Ferrières and Yves-Henri Sanejouand and Charles Tellier},
doi = {10.1093/glycob/cwu124},
issn = {14602423},
year  = {2015},
date = {2015-01-01},
journal = {Glycobiology},
volume = {25},
number = {4},
pages = {420--427},
abstract = {A large number of retaining glycosidases catalyze both hydrolysis and transglycosylation reactions. In order to use them as catalysts for oligosaccharide synthesis, the balance between these two competing reactions has to be shifted toward transglycosylation. We previously designed a semi-rational approach to convert the Thermus thermophilus β-glycosidases into transglycosidases by mutating highly conserved residues located around the -1 subsite. In an attempt to verify that this strategy could be a generic approach to turn glycosidases into transglycosidases, Geobacillus stearothermophilus α-galactosidase (AgaB) was selected in order to obtain α-transgalactosidases. This is of particular interest as, to date, there are no efficient α-galactosynthases, despite the considerable importance of α-galactooligosaccharides. Thus, by site-directed mutagenesis on 14 AgaB residues, 26 single mutants and 22 double mutants were created and screened, of which 11 single mutants and 6 double mutants exhibited improved synthetic activity, producing 4-nitrophenyl α-d-galactopyranosyl-(1,6)-α-d-galactopyranoside in 26-57% yields against only 22% when native AgaB was used. It is interesting to note that the best variant was obtained by mutating a second-shell residue, with no direct interaction with the substrate or a catalytic amino acid. As this approach has proved to be efficient with both α- and β-glycosidases, it is a promising route to convert retaining glycosidases into transglycosidases.},
keywords = {evolution, glycosidase, mutagenesis, oligosaccharide, team 1, team 2, Transglycosylation},
pubstate = {published},
tppubtype = {article}
}
@article{Saumonneau2015a,
title = {Design of an α-l-transfucosidase for the synthesis of fucosylated HMOs},
author = {Amélie Saumonneau and Elise Champion and Pauline Peltier-Pain and Dora Molnar-Gabor and Johann Hendrickx and Vinh Tran and Markus Hederos and Gyula Dekany and Charles Tellier},
doi = {10.1093/glycob/cwv099},
issn = {14602423},
year  = {2015},
date = {2015-01-01},
journal = {Glycobiology},
volume = {26},
number = {3},
pages = {261--269},
abstract = {Human milk oligosaccharides (HMOs) are recognized as benefiting breast-fed infants in multiple ways. As a result, there is growing interest in the synthesis of HMOs mimicking their natural diversity. Most HMOs are fucosylated oligosaccharides. α-l-Fucosidases catalyze the hydrolysis of α-l-fucose from the non-reducing end of a glucan. They fall into the glycoside hydrolase GH29 and GH95 families. The GH29 family fucosidases display a classic retaining mechanism and are good candidates for transfucosidase activity. We recently demonstrated that the α-l-fucosidase from Thermotoga maritima (TmαFuc) from the GH29 family can be evolved into an efficient transfucosidase by directed evolution (Osanjo et al. 2007). In this work, we developed semi-rational approaches to design an α-l-transfucosidase starting with the α-l-fucosidase from commensal bacteria Bifidobacterium longum subsp. infantis (BiAfcB, Blon-2336). Efficient fucosylation was obtained with enzyme mutants (L321P-BiAfcB and F34I/L321P-BiAfcB) enabling in vitro synthesis of lactodifucotetraose, lacto-N-fucopentaose II, lacto-N-fucopentaose III and lacto-N-difucohexaose I. The enzymes also generated more complex HMOs like fucosylated para-lacto-N-neohexaose (F-p-LNnH) and mono- or difucosylated lacto-N-neohexaose (F-LNnH-I, F-LNnH-II and DF-LNnH). It is worth noting that mutation at these two positions did not result in a strong decrease in the overall activity of the enzyme, which makes these variants interesting candidates for large-scale transfucosylation reactions. For the first time, this work provides an efficient enzymatic method to synthesize the majority of fucosylated HMOs.},
keywords = {Bifidobacterium longum subsp. infantis, d-zyme, enzymatic synthesis, fucosidase, Human milk oligosaccharides, team 1, team 2, transfucosylation},
pubstate = {published},
tppubtype = {article}
}
@article{Craveur2015,
title = {Protein flexibility in the light of structural alphabets},
author = {Pierrick Craveur and Agnel P Joseph and Jeremy Esque and Tarun J Narwani and Floriane Noël and Nicolas Shinada and Matthieu Goguet and Sylvain Leonard and Pierre Poulain and Olivier Bertrand and Guilhem Faure and Joseph Rebehmed and Amine Ghozlane and Lakshmipuram S Swapna and Ramachandra M Bhaskara and Jonathan Barnoud and Stéphane Téletchéa and Vincent Jallu and Jiri Cerny and Bohdan Schneider and Catherine Etchebest and Narayanaswamy Srinivasan and Jean Christophe Gelly and Alexandre G de Brevern},
doi = {10.3389/fmolb.2015.00020},
issn = {2296889X},
year  = {2015},
date = {2015-01-01},
journal = {Frontiers in Molecular Biosciences},
volume = {2},
number = {MAY},
pages = {1--20},
abstract = {Protein structures are valuable tools to understand protein function. Nonetheless, proteins are often considered as rigid macromolecules while their structures exhibit specific flexibility, which is essential to complete their functions. Analyses of protein structures and dynamics are often performed with a simplified three-state description, i.e., the classical secondary structures. More precise and complete description of protein backbone conformation can be obtained using libraries of small protein fragments that are able to approximate every part of protein structures. These libraries, called structural alphabets (SAs), have been widely used in structure analysis field, from definition of ligand binding sites to superimposition of protein structures. SAs are also well suited to analyze the dynamics of protein structures. Here, we review innovative approaches that investigate protein flexibility based on SAs description. Coupled to various sources of experimental data (e.g., B-factor) and computational methodology (e.g., Molecular Dynamic simulation), SAs turn out to be powerful tools to analyze protein dynamics, e.g., to examine allosteric mechanisms in large set of structures in complexes, to identify order/disorder transition. SAs were also shown to be quite efficient to predict protein flexibility from amino-acid sequence. Finally, in this review, we exemplify the interest of SAs for studying flexibility with different cases of proteins implicated in pathologies and diseases.},
keywords = {Allostery, Disorder, Protein complexes, Protein folding, protein structures, Protein-DNA interactions, Secondary structure, Structural alphabet, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{Fontaine2015,
title = {Modeling of a Cell-Free Synthetic System for Biohydrogen Production},
author = {Nicolas Fontaine and Brigitte Grondin-perez and Frédéric Cadet and Bernard Offmann and Nicolas Fontaine and Brigitte Grondin-perez and Frédéric Cadet and Bernard Offmann and Nicolas Fontaine and Brigitte Grondin-perez and Frédéric Cadet and Bernard Offmann},
doi = {10.4172/jcsb.1000181},
issn = {09747230},
year  = {2015},
date = {2015-01-01},
journal = {Journal of Computer Science & Systems Biology},
volume = {8},
number = {3},
abstract = {Hydrogen is a good candidate for the next generation fuel with a high energy density and an environment friendly behavior in the energy production phase. Micro-organism based biological production of hydrogen currently suffers low hydrogen production yields because the living cells must sustain different cellular activities other than the hydrogen production to survive. To circumvent this, teams have explored the synthetic assembly of enzymes in-vitro in cell-free systems with specific functions. Such a synthetic cell-free system was recently devised by combining 13 different enzymes to synthesize hydrogen from cellulose or cellobiose with better yield than microorganism-based systems. We used methods based on differential equations calculations to investigate how the initial conditions and the kinetic parameters of the enzymes influenced the productivity of a such system and, through simulations, identified those conditions that would optimize hydrogen production starting with cellobiose as substrate. Further, if the kinetic parameters of the component enzymes of such a system are not known, we showed how, using artificial neural network, it is possible to identify alternative models that account for the rate of production of hydrogen. This work demonstrates how modeling can help in designing and characterizing cell-free systems in synthetic biology. A web-based simulator implementing our differential equations based model is provided freely as a service for non- commercial usage at http://www.bo-protscience.fr/h2.},
keywords = {artificial neural network, biochemical engineering, cell-free synthetic system, hydrogen production, mathematical modeling, optimization, simulation, system, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{Le-Bail2015,
title = {Trapping by amylose of the aliphatic chain grafted onto chlorogenic acid: Importance of the graft position},
author = {Patricia Le-Bail and C Lorentz and G Pencreac'h and S Soultani-Vigneron and B Pontoire and J.López L Giraldo and P Villeneuve and Johann Hendrickx and Vinh Tran},
url = {http://dx.doi.org/10.1016/j.carbpol.2014.10.029},
doi = {10.1016/j.carbpol.2014.10.029},
issn = {01448617},
year  = {2015},
date = {2015-01-01},
journal = {Carbohydrate Polymers},
volume = {117},
pages = {910--916},
publisher = {Elsevier Ltd.},
abstract = {5-Caffeoylquinic acid (chlorogenic acid), is classified in acid-phenols family and as polyphenolic compounds it possesses antioxidant activity. The oxydative modification of chlorogenic acid in foods may lead to alteration of their qualities; to counteract these degradation effects, molecular encapsulation was used to protect chlorogenic acid. Amylose can interact strongly with a number of small molecules, including lipids. In order to enable chlorogenic acid complexation by amylose, a C16 aliphatic chain was previously grafted onto the cycle of quinic acid. This work showed that for the two lipophilic derivatives of chlorogenic acid: hexadecyl chlorogenate obtained by alkylation and 3-O-palmitoyl chlorogenic acid obtained by acylation; only the 3-O-palmitoyl chlorogenic acid complexed amylose. The chlorogenic acid derivatives were studied by X-ray diffraction, differential scanning calorimetry and NMR to elucidate the interaction. By comparing the results with previous work on the complexation of amylose by 4-O-palmitoyl chlorogenic acid, the importance of the aliphatic chain position on the cycle of the quinic acid is clearly highlighted. A study in molecular modeling helped to understand the difference in behavior relative to amylose of these three derivatives of chlorogenic acid.},
keywords = {Amylose complex, CP/MAS NMR, DSC, Molecular modeling, Palmitoyl chlorogenic acid, team 1, X-ray diffraction},
pubstate = {published},
tppubtype = {article}
}
@article{EQ2:CAMBERLEIN:2015,
title = {Importance of Bacterial Replication and Alveolar Macrophage-Independent Clearance Mechanisms during Early Lung Infection with Streptococcus pneumoniae},
author = {Emilie Camberlein and Jonathan M Cohen and Ricardo José and Catherine J Hyams and Robin Callard and Suneeta Chimalapati and Jose Yuste and Lindsey A Edwards and Helina Marshall and Nico van Rooijen and Mahdad Noursadeghi and Jeremy S Brown},
editor = {A Camilli},
url = {https://iai.asm.org/content/83/3/1181},
doi = {10.1128/IAI.02788-14},
issn = {0019-9567},
year  = {2015},
date = {2015-01-01},
journal = {Infection and Immunity},
volume = {83},
number = {3},
pages = {1181--1189},
publisher = {American Society for Microbiology Journals},
abstract = {Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors are less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated, and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, capsule, and alveolar macrophage-dependent and -independent clearance mechanisms on bacterial persistence within the lungs. Alveolar macrophage-dependent and -independent (calculated indirectly) clearance half-lives and bacterial replication doubling times were estimated using a mathematical model. In this model, after infection with a high-dose inoculum of encapsulated S. pneumoniae, alveolar macrophage-independent clearance mechanisms were dominant, with a clearance half-life of 24 min compared to 135 min for alveolar macrophage-dependent clearance. In addition, after a high-dose inoculum, successful lung infection required rapid bacterial replication, with an estimated S. pneumoniae doubling time of 16 min. The capsule had wide effects on early lung clearance mechanisms, with reduced half-lives of 14 min for alveolar macrophage-independent and 31 min for alveolar macrophage-dependent clearance of unencapsulated bacteria. In contrast, with a lower-dose inoculum, the bacterial doubling time increased to 56 min and the S. pneumoniae alveolar macrophage-dependent clearance half-life improved to 42 min and was largely unaffected by the capsule. These data demonstrate the large effects of bacterial factors (inoculum size, the capsule, and rapid replication) and alveolar macrophage-independent clearance mechanisms during early lung infection with S. pneumoniae.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{avEQ5:TIRICHINE:2015a,
title = {Membrane Glycerolipid Remodeling Triggered by Nitrogen and Phosphorus Starvation in Phaeodactylum tricornutum,},
author = {Heni Abida and Lina-Juana Dolch and Coline Meï and Valeria Villanova and Melissa Conte and Maryse A Block and Giovanni Finazzi and Olivier Bastien and Leila Tirichine and Chris Bowler and Fabrice Rébeillé and Dimitris Petroutsos and Juliette Jouhet and Eric Maréchal},
url = {http://www.plantphysiol.org/content/167/1/118},
doi = {10.1104/pp.114.252395},
issn = {0032-0889},
year  = {2015},
date = {2015-01-01},
journal = {Plant Physiology},
volume = {167},
number = {1},
pages = {118--136},
publisher = {American Society of Plant Biologists},
abstract = {Diatoms constitute a major phylum of phytoplankton biodiversity in ocean water and freshwater ecosystems. They are known to respond to some chemical variations of the environment by the accumulation of triacylglycerol, but the relative changes occurring in membrane glycerolipids have not yet been studied. Our goal was first to define a reference for the glycerolipidome of the marine model diatom Phaeodactylum tricornutum,, a necessary prerequisite to characterize and dissect the lipid metabolic routes that are orchestrated and regulated to build up each subcellular membrane compartment. By combining multiple analytical techniques, we determined the glycerolipid profile of emphP. tricornutum, grown with various levels of nitrogen or phosphorus supplies. In different emphP. tricornutum, accessions collected worldwide, a deprivation of either nutrient triggered an accumulation of triacylglycerol, but with different time scales and magnitudes. We investigated in depth the effect of nutrient starvation on the Pt1 strain (Culture Collection of Algae and Protozoa no. 1055/3). Nitrogen deprivation was the more severe stress, triggering thylakoid senescence and growth arrest. By contrast, phosphorus deprivation induced a stepwise adaptive response. The time scale of the glycerolipidome changes and the comparison with large-scale transcriptome studies were consistent with an exhaustion of unknown primary phosphorus-storage molecules (possibly polyphosphate) and a transcriptional control of some genes coding for specific lipid synthesis enzymes. We propose that phospholipids are secondary phosphorus-storage molecules broken down upon phosphorus deprivation, while nonphosphorus lipids are synthesized consistently with a phosphatidylglycerol-to-sulfolipid and a phosphatidycholine-to-betaine lipid replacement followed by a late accumulation of triacylglycerol.GlossaryNnitrogenPphosphorusPCphosphatidylcholinePGphosphatidylglycerolSQDGsulfoquinovosyldiacylglycerolBLbetaine lipidsMGDGmonogalactosyldiacylglycerolDGDGdigalactosyldiacylglycerolTAGtriacylglycerolDAGdiacylglycerolERendoplasmic reticulumPEphosphatidylethanolamineFv/Fmphotosynthetic capacityFAMEfatty acid methyl esterGC-FIDgas chromatography and flame ionization detectionFAfatty acidMSmass spectrometryDGTAdiacylglyceryl-hydroxymethyl-N,N,N-trimethyl-β-alanineDGTSdiacylglyceryl-N,N,N-trimethylhomoserinem/zmass-to-charge ratioMS2tandem mass spectrometryPIphosphatidylinositideCDP-DAGcytidine diphosphate-diacylglycerolESAWenriched seawater, artificial water},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{avEQ5:TANAKA_TIRICHINE:2015,
title = {Ultrastructure and Membrane Traffic During Cell Division in the Marine Pennate Diatom Phaeodactylum tricornutum,},
author = {Atsuko Tanaka and Alessandra De Martino and Alberto Amato and Anton Montsant and Benjamin Mathieu and Philippe Rostaing and Leila Tirichine and Chris Bowler},
url = {http://www.sciencedirect.com/science/article/pii/S1434461015000498},
doi = {https://doi.org/10.1016/j.protis.2015.07.005},
issn = {1434-4610},
year  = {2015},
date = {2015-01-01},
journal = {Protist},
volume = {166},
number = {5},
pages = {506 - 521},
abstract = {The marine pennate diatom Phaeodactylum tricornutum, has become a model for diatom biology, due to its ease of culture and accessibility to reverse genetics approaches. While several features underlying the molecular mechanisms of cell division have been described, morphological analyses are less advanced than they are in other diatoms. We therefore examined cell ultrastructure changes prior to and during cytokinesis. Following chloroplast division, cleavage furrows are formed at both longitudinal ends of the cell and are accompanied by significant vesicle transport. Although neither spindle nor microtubules were observed, the nucleus appeared to be split by the furrow after duplication of the Golgi apparatus. Finally, centripetal cytokinesis was completed by fusion of the furrows. Additionally, F-actin formed a ring structure and its diameter became smaller, accompanying the ingrowing furrows. To further analyse vesicular transport during cytokinesis, we generated transgenic cells expressing yellow fluorescent protein (YFP) fusions with putative diatom orthologs of small GTPase Sec4 and t-SNARE protein SyntaxinA. Time-lapse observations revealed that SyntaxinA-YFP localization expands from both cell tips toward the center, whereas Sec4-YFP was found in the Golgi and subsequently relocalizes to the future division plane. This work provides fundamental new information about cell replication processes in emphP. tricornutum,.},
keywords = {actin, contractile ring., cytokinesis, Diatom, out_lab, Sec4, Syntaxin},
pubstate = {published},
tppubtype = {article}
}
@article{EQ5:Groisillier:2015,
title = {Determination of Fructokinase Activity from Zobellia galactanivorans},
author = {Agnès Groisillier and Thierry Tonon},
url = {https://doi.org/10.21769/bioprotoc.1633},
doi = {10.21769/bioprotoc.1633},
year  = {2015},
date = {2015-01-01},
journal = {BIO-PROTOCOL},
volume = {5},
number = {21},
publisher = {Bio-Protocol, LLC},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{EQ5:Groisillier:2015b,
title = {Determination of Mannitol-2-dehydrogenase Activity},
author = {Agnès Groisillier and Thierry Tonon},
url = {https://doi.org/10.21769/bioprotoc.1634},
doi = {10.21769/bioprotoc.1634},
year  = {2015},
date = {2015-01-01},
journal = {BIO-PROTOCOL},
volume = {5},
number = {21},
publisher = {Bio-Protocol, LLC},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{EQ5:Groisillier:2015d,
title = {The Mannitol Utilization System of the Marine Bacterium Zobellia galactanivorans},
author = {Agnès Groisillier and Aurore Labourel and Gurvan Michel and Thierry Tonon},
editor = {H Nojiri},
url = {https://aem.asm.org/content/81/5/1799},
doi = {10.1128/AEM.02808-14},
issn = {0099-2240},
year  = {2015},
date = {2015-01-01},
journal = {Applied and Environmental Microbiology},
volume = {81},
number = {5},
pages = {1799--1812},
publisher = {American Society for Microbiology Journals},
abstract = {Mannitol is a polyol that occurs in a wide range of living organisms, where it fulfills different physiological roles. In particular, mannitol can account for as much as 20 to 30% of the dry weight of brown algae and is likely to be an important source of carbon for marine heterotrophic bacteria. Zobellia galactanivorans (Flavobacteriia) is a model for the study of pathways involved in the degradation of seaweed carbohydrates. Annotation of its genome revealed the presence of genes potentially involved in mannitol catabolism, and we describe here the biochemical characterization of a recombinant mannitol-2-dehydrogenase (M2DH) and a fructokinase (FK). Among the observations, the M2DH of Z. galactanivorans was active as a monomer, did not require metal ions for catalysis, and featured a narrow substrate specificity. The FK characterized was active on fructose and mannose in the presence of a monocation, preferentially K+. Furthermore, the genes coding for these two proteins were adjacent in the genome and were located directly downstream of three loci likely to encode an ATP binding cassette (ABC) transporter complex, suggesting organization into an operon. Gene expression analysis supported this hypothesis and showed the induction of these five genes after culture of Z. galactanivorans in the presence of mannitol as the sole source of carbon. This operon for mannitol catabolism was identified in only 6 genomes of Flavobacteriaceae among the 76 publicly available at the time of the analysis. It is not conserved in all Bacteroidetes; some species contain a predicted mannitol permease instead of a putative ABC transporter complex upstream of M2DH and FK ortholog genes.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{EQ5:GROISILLIER:2015e,
title = {Biochemical and structural investigation of two paralogous glycoside hydrolases from Zobellia galactanivorans: novel insights into the evolution, dimerization plasticity and catalytic mechanism of the GH117 family},
author = {Elizabeth Ficko-Blean and Delphine Duffieux and Étienne Rebuffet and Robert Larocque and Agnes Groisillier and Gurvan Michel and Mirjam Czjzek},
url = {https://doi.org/10.1107%2Fs1399004714025024},
doi = {10.1107/s1399004714025024},
year  = {2015},
date = {2015-01-01},
journal = {Acta Crystallographica Section D Biological Crystallography},
volume = {71},
number = {2},
pages = {209--223},
publisher = {International Union of Crystallography (IUCr)},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{EQ4:DUC:2015,
title = {The histone chaperone complex HIR maintains nucleosome occupancy and counterbalances impaired histone deposition in CAF-1 complex mutants},
author = {Céline Duc and Matthias Benoit and Samuel Le Goff and Lauriane Simon and Axel Poulet and Sylviane Cotterell and Christophe Tatout and Aline V Probst},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/tpj.12758},
doi = {10.1111/tpj.12758},
year  = {2015},
date = {2015-01-01},
journal = {The Plant Journal},
volume = {81},
number = {5},
pages = {707-722},
abstract = {Summary Chromatin organization is essential for coordinated gene expression, genome stability, and inheritance of epigenetic information. The main components involved in chromatin assembly are specific complexes such as Chromatin Assembly Factor 1 (CAF-1) and Histone Regulator (HIR), which deposit histones in a DNA synthesis-dependent or -independent manner, respectively. Here, we characterize the role of the plant orthologs Histone Regulator A (HIRA), Ubinuclein (UBN) and Calcineurin Binding protein 1 (CABIN1), which constitute the HIR complex. Arabidopsis loss-of-function mutants for the various subunits of the complex are viable, but hira mutants show reduced fertility. We show that loss of HIRA reduces extractable histone H3 protein levels and decreases nucleosome occupancy at both actively transcribed genes and heterochromatic regions. Concomitantly, HIRA contributes to maintenance of silencing of pericentromeric repeats and certain transposons. A genetic analysis based on crosses between mutants deficient in subunits of the CAF-1 and HIR complexes showed that simultaneous loss of both the CAF-1 and HIR histone H3 chaperone complexes severely affects plant survival, growth and reproductive development. Our results suggest that HIRA partially rescues impaired histone deposition in fas mutants to preserve nucleosome occupancy, implying plasticity in histone variant interaction and deposition.},
keywords = {Arabidopsis, chaperone, histone, nucleosome, out_lab, transcriptional silencing},
pubstate = {published},
tppubtype = {article}
}
@article{pmid25208912,
title = {Assessment of DNA binding to human Rad51 protein by using quartz crystal microbalance and atomic force microscopy: effects of ADP and BRC4-28 peptide inhibitor},
author = {Charles Esnault and Axelle Renodon-Cornière and Masayuki Takahashi and Nathalie Casse and Nicolas Delorme and Guy Louarn and Fabrice Fleury and Jean-François Pilard and Benoît Chénais},
doi = {10.1002/cphc.201402451},
issn = {1439-7641},
year  = {2014},
date = {2014-12-01},
urldate = {2014-12-01},
journal = {Chemphyschem},
volume = {15},
number = {17},
pages = {3753--3760},
abstract = {The interaction of human Rad51 protein (HsRad51) with single-stranded deoxyribonucleic acid (ssDNA) was investigated by using quartz crystal microbalance (QCM) monitoring and atomic force microscopy (AFM) visualization. Gold surfaces for QCM and AFM were modified by electrografting of the in situ generated aryldiazonium salt from the sulfanilic acid to obtain the organic layer Au-ArSO3 H. The Au-ArSO3 H layer was activated by using a solution of PCl5 in CH2 Cl2 to give a Au-ArSO2 Cl layer. The modified surface was then used to immobilize long ssDNA molecules. The results obtained showed that the presence of adenosine diphosphate promotes the protein autoassociation rather than nucleation around DNA. In addition, when the BRC4-28 peptide inhibitor was used, both QCM and AFM confirmed the inhibitory effect of BRC4-28 toward HsRad51 autoassociation. Altogether these results show the suitability of this modified surface to investigate the kinetics and structure of DNA-protein interactions and for the screening of inhibitors. },
keywords = {out_lab, team 3},
pubstate = {published},
tppubtype = {article}
}
@article{Berland:2014aa,
title = {A web-based tool for rational screening of mutants libraries using ProSAR},
author = {Magali Berland and Bernard Offmann and Isabelle André and Magali Remaud-Siméon and Philippe Charton},
doi = {10.1093/protein/gzu035},
year  = {2014},
date = {2014-10-01},
urldate = {2014-10-01},
journal = {Protein Eng Des Sel},
volume = {27},
number = {10},
pages = {375-81},
abstract = {In directed evolution experiments, it is at stake to have methods to screen efficiently the mutant libraries. We propose a web-based tool that implements an established in silico method for the rational screening of mutant libraries. The method, known as ProSAR, attempts to link sequence data to activity. The method uses statistical models trained on small experimental datasets provided by the user. These can integrate potential epistatic interactions between mutations and be used in many diverse biological contexts. It drastically improves the search for leading mutants. The tool is freely available to non-commercial users at http://bo-protscience.fr/prosar/.},
keywords = {fitness landscape exploration, out_lab, protein engineering, rational screening, sequence--activity relationship, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{pmid24879542,
title = {Marennine, promising blue pigments from a widespread Haslea diatom species complex},
author = {Romain Gastineau and François Turcotte and Jean-Bernard Pouvreau and Michèle Morançais and Joël Fleurence and Eko Windarto and Fiddy Semba Prasetiya and Sulastri Arsad and Pascal Jaouen and Mathieu Babin and Laurence Coiffard and Céline Couteau and Jean-François Bardeau and Boris Jacquette and Vincent Leignel and Yann Hardivillier and Isabelle Marcotte and Nathalie Bourgougnon and Réjean Tremblay and Jean-Sébastien Deschênes and Hope Badawy and Pamela Pasetto and Nikolai Davidovich and Gert Hansen and Jens Dittmer and Jean-Luc Mouget},
doi = {10.3390/md12063161},
issn = {1660-3397},
year  = {2014},
date = {2014-05-01},
urldate = {2014-05-01},
journal = {Mar Drugs},
volume = {12},
number = {6},
pages = {3161--3189},
abstract = {In diatoms, the main photosynthetic pigments are chlorophylls a and c, fucoxanthin, diadinoxanthin and diatoxanthin. The marine pennate diatom Haslea ostrearia has long been known for producing, in addition to these generic pigments, a water-soluble blue pigment, marennine. This pigment, responsible for the greening of oysters in western France, presents different biological activities: allelopathic, antioxidant, antibacterial, antiviral, and growth-inhibiting. A method to extract and purify marennine has been developed, but its chemical structure could hitherto not be resolved. For decades, H. ostrearia was the only organism known to produce marennine, and can be found worldwide. Our knowledge about H. ostrearia-like diatom biodiversity has recently been extended with the discovery of several new species of blue diatoms, the recently described H. karadagensis, H. silbo sp. inedit. and H. provincialis sp. inedit. These blue diatoms produce different marennine-like pigments, which belong to the same chemical family and present similar biological activities. Aside from being a potential source of natural blue pigments, H. ostrearia-like diatoms thus present a commercial potential for aquaculture, cosmetics, food and health industries.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid24249726,
title = {New strigolactone analogs as plant hormones with low activities in the rhizosphere},
author = {François-Didier Boyer and Alexandre de Saint Germain and Jean-Bernard Pouvreau and Guillaume Clavé and Jean-Paul Pillot and Amélie Roux and Amanda Rasmussen and Stephen Depuydt and Dominique Lauressergues and Nicolas Frei Dit Frey and Thomas S A Heugebaert and Christian V Stevens and Danny Geelen and Sofie Goormachtig and Catherine Rameau},
doi = {10.1093/mp/sst163},
issn = {1752-9867},
year  = {2014},
date = {2014-04-01},
urldate = {2014-04-01},
journal = {Mol Plant},
volume = {7},
number = {4},
pages = {675--690},
abstract = {Strigolactones (SLs) are known not only as plant hormones, but also as rhizosphere signals for establishing symbiotic and parasitic interactions. The design of new specific SL analogs is a challenging goal in understanding the basic plant biology and is also useful to control plant architectures without favoring the development of parasitic plants. Two different molecules (23 (3&#039;-methyl-GR24), 31 (thia-3&#039;-methyl-debranone-like molecule)) already described, and a new one (AR36), for which the synthesis is presented, are biologically compared with the well-known GR24 and the recently identified CISA-1. These different structures emphasize the wide range of parts attached to the D-ring for the bioactivity as a plant hormone. These new compounds possess a common dimethylbutenolide motif but their structure varies in the ABC part of the molecules: 23 has the same ABC part as GR24, while 31 and AR36 carry, respectively, an aromatic ring and an acyclic carbon chain. Detailed information is given for the bioactivity of such derivatives in strigolactone synthesis or in perception mutant plants (pea rms1 and rms4, Arabidopsis max2 and, max4) for different hormonal functions along with their action in the rhizosphere on arbuscular mycorrhizal hyphal growth and parasitic weed germination.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Mahajan:2014aa,
title = {Correlation between local structural dynamics of proteins inferred from NMR ensembles and evolutionary dynamics of homologues of known structure},
author = {Swapnil Mahajan and Alexandre G {de Brevern} and Bernard Offmann and Narayanaswamy Srinivasan},
doi = {10.1080/07391102.2013.789989},
year  = {2014},
date = {2014-01-01},
journal = {J Biomol Struct Dyn},
volume = {32},
number = {5},
pages = {751-8},
abstract = {Conformational changes in proteins are extremely important for their biochemical functions. Correlation between inherent conformational variations in a protein and conformational differences in its homologues of known structure is still unclear. In this study, we have used a structural alphabet called Protein Blocks (PBs). PBs are used to perform abstraction of protein 3-D structures into a 1-D strings of 16 alphabets (a-p) based on dihedral angles of overlapping pentapeptides. We have analyzed the variations in local conformations in terms of PBs represented in the ensembles of 801 protein structures determined using NMR spectroscopy. In the analysis of concatenated data over all the residues in all the NMR ensembles, we observe that the overall nature of inherent local structural variations in NMR ensembles is similar to the nature of local structural differences in homologous proteins with a high correlation coefficient of .94. High correlation at the alignment positions corresponding to helical and β-sheet regions is only expected. However, the correlation coefficient by considering only the loop regions is also quite high (.91). Surprisingly, segregated position-wise analysis shows that this high correlation does not hold true to loop regions at the structurally equivalent positions in NMR ensembles and their homologues of known structure. This suggests that the general nature of local structural changes is unique; however most of the local structural variations in loop regions of NMR ensembles do not correlate to their local structural differences at structurally equivalent positions in homologues.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Manoharan:2014aa,
title = {Insights on pH-dependent conformational changes of mosquito odorant binding proteins by molecular dynamics simulations},
author = {Malini Manoharan and Patrick F J Fuchs and Ramanathan Sowdhamini and Bernard Offmann},
doi = {10.1080/07391102.2013.834118},
year  = {2014},
date = {2014-01-01},
journal = {J Biomol Struct Dyn},
volume = {32},
number = {11},
pages = {1742-51},
abstract = {Chemical recognition plays an important role for the survival and reproduction of many insect species. Odorant binding proteins (OBPs) are the primary components of the insect olfactory mechanism and have been documented to play an important role in the host-seeking mechanism of mosquitoes. They are "transport proteins" believed to transport odorant molecules from the external environment to their respective membrane targets, the olfactory receptors. The mechanism by which this transport occurs in mosquitoes remains a conundrum in this field. Nevertheless, OBPs have proved to be amenable to conformational changes mediated by a pH change in other insect species. In this paper, the effect of pH on the conformational flexibility of mosquito OBPs is assessed computationally using molecular dynamics simulations of a mosquito OBP "CquiOBP1" bound to its pheromone 3OG (PDB ID: 3OGN). Conformational twist of a loop, driven by a set of well-characterized changes in intramolecular interactions of the loop, is demonstrated. The concomitant (i) closure of what is believed to be the entrance of the binding pocket, (ii) expansion of what could be an exit site, and (iii) migration of the ligand towards this putative exit site provide preliminary insights into the mechanism of ligand binding and release of these proteins in mosquitoes. The correlation of our results with previous experimental observations based on NMR studies help us provide a cardinal illustration on one of the probable dynamics and mechanism by which certain mosquito OBPs could deliver their ligand to their membrane-bound receptors at specific pH conditions.},
keywords = {out_lab, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{Pradervand3971,
title = {The TetR-Type MfsR Protein of the Integrative and Conjugative Element (ICE) ICEclc Controls both a Putative Efflux System and Initiation of ICE Transfer},
author = {Nicolas Pradervand and François Delavat and Sandra Sulser and Ryo Miyazaki and Jan Roelof van der Meer},
url = {https://jb.asm.org/content/196/22/3971},
doi = {10.1128/JB.02129-14},
issn = {0021-9193},
year  = {2014},
date = {2014-01-01},
journal = {Journal of Bacteriology},
volume = {196},
number = {22},
pages = {3971--3979},
publisher = {American Society for Microbiology Journals},
abstract = {Integrative and conjugating elements (ICE) are self-transferable DNAs widely present in bacterial genomes, which often carry a variety of auxiliary genes of potential adaptive benefit. One of the model ICE is ICEclc, an element originally found in Pseudomonas knackmussii B13 and known for its propensity to provide its host with the capacity to metabolize chlorocatechols and 2-aminophenol. In this work, we studied the mechanism and target of regulation of MfsR, a TetR-type repressor previously found to exert global control on ICEclc horizontal transfer. By using a combination of ICEclc mutant and transcriptome analysis, gene reporter fusions, and DNA binding assays, we found that MfsR is a repressor of both its own expression and that of a gene cluster putatively coding for a major facilitator superfamily efflux system on ICEclc (named mfsABC). Phylogenetic analysis suggests that mfsR was originally located immediately adjacent to the efflux pump genes but became displaced from its original cis target DNA by a gene insertion. This resulted in divergence of the original bidirectional promoters into two separated individual regulatory units. Deletion of mfsABC did not result in a strong phenotype, and despite screening a large number of compounds and conditions, we were unable to define the precise current function or target of the putative efflux pump. Our data reconstruct how the separation of an ancestor mfsR-mfsABC system led to global control of ICEclc transfer by MfsR.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pradervand2014operon,
title = {An operon of three transcriptional regulators controls horizontal gene transfer of the integrative and conjugative element ICE clc in Pseudomonas knackmussii B13},
author = {Nicolas Pradervand and Sandra Sulser and François Delavat and Ryo Miyazaki and Iker Lamas and Jan Roelof van der Meer},
url = {https://doi.org/10.1371/journal.pgen.1004441},
doi = {10.1371/journal.pgen.1004441},
year  = {2014},
date = {2014-01-01},
journal = {PLoS Genet},
volume = {10},
number = {6},
pages = {e1004441},
publisher = {Public Library of Science},
abstract = {The integrative and conjugative element ICEclc is a mobile genetic element in Pseudomonas knackmussii B13, and an experimental model for a widely distributed group of elements in Proteobacteria. ICEclc is transferred from specialized transfer competent cells, which arise at a frequency of 3-5% in a population at stationary phase. Very little is known about the different factors that control the transfer frequency of this ICE family. Here we report the discovery of a three-gene operon encoded by ICEclc, which exerts global control on transfer initiation. The operon consists of three consecutive regulatory genes, encoding a TetR-type repressor MfsR, a MarR-type regulator and a LysR-type activator TciR. We show that MfsR autoregulates expression of the operon, whereas TciR is a global activator of ICEclc gene expression, but no clear role was yet found for MarR. Deletion of mfsR increases expression of tciR and marR, causing the proportion of transfer competent cells to reach almost 100% and transfer frequencies to approach 1 per donor. mfsR deletion also caused a two orders of magnitude loss in population viability, individual cell growth arrest and loss of ICEclc. This indicates that autoregulation is an important feature maintaining ICE transfer but avoiding fitness loss. Bioinformatic analysis showed that the mfsR-marR-tciR operon is unique for ICEclc and a few highly related ICE, whereas tciR orthologues occur more widely in a large variety of suspected ICE among Proteobacteria.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Tomlinson3736,
title = {TLR-Mediated Inflammatory Responses to Streptococcus pneumoniae Are Highly Dependent on Surface Expression of Bacterial Lipoproteins},
author = {Gillian Tomlinson and Suneeta Chimalapati and Tracey Pollard and Thabo Lapp and Jonathan Cohen and Emilie Camberlein and Sian Stafford and Jimstan Periselneris and Christine Aldridge and Waldemar Vollmer and Capucine Picard and Jean-Laurent Casanova and Mahdad Noursadeghi and Jeremy Brown},
url = {https://www.jimmunol.org/content/193/7/3736},
doi = {10.4049/jimmunol.1401413},
issn = {0022-1767},
year  = {2014},
date = {2014-01-01},
journal = {The Journal of Immunology},
volume = {193},
number = {7},
pages = {3736--3745},
publisher = {American Association of Immunologists},
abstract = {Streptococcus pneumoniae infections induce inflammatory responses that contribute toward both disease pathogenesis and immunity, but the host–pathogen interactions that mediate these effects are poorly defined. We used the surface lipoprotein-deficient ∆lgt pneumococcal mutant strain to test the hypothesis that lipoproteins are key determinants of TLR-mediated immune responses to S. pneumoniae. We show using reporter assays that TLR2 signaling is dependent on pneumococcal lipoproteins, and that macrophage NF-κB activation and TNF-α release were reduced in response to the ∆lgt strain. Differences in TNF-α responses between Δlgt and wild-type bacteria were abrogated for macrophages from TLR2- but not TLR4-deficient mice. Transcriptional profiling of human macrophages revealed attenuated TLR2-associated responses to ∆lgt S. pneumoniae, comprising many NF-κB–regulated proinflammatory cytokine and chemokine genes. Importantly, non-TLR2–associated responses were preserved. Experiments using leukocytes from IL-1R–associated kinase-4–deficient patients and a mouse pneumonia model confirmed that proinflammatory responses were lipoprotein dependent. Our data suggest that leukocyte responses to bacterial lipoproteins are required for TLR2- and IL-1R-associated kinase-4-mediated inflammatory responses to S. pneumoniae.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{COLLEN20146199,
title = {A Novel Unsaturated β-Glucuronyl Hydrolase Involved in Ulvan Degradation Unveils the Versatility of Stereochemistry Requirements in Family GH105*},
author = {Pi Nyvall Collén and Alexandra Jeudy and Jean-François Sassi and Agnès Groisillier and Mirjam Czjzek and Pedro M Coutinho and William Helbert},
url = {https://www.sciencedirect.com/science/article/pii/S0021925820440797},
doi = {https://doi.org/10.1074/jbc.M113.537480},
issn = {0021-9258},
year  = {2014},
date = {2014-01-01},
journal = {Journal of Biological Chemistry},
volume = {289},
number = {9},
pages = {6199-6211},
abstract = {Ulvans are cell wall matrix polysaccharides in green algae belonging to the genus Ulva. Enzymatic degradation of the polysaccharide by ulvan lyases leads to the production of oligosaccharides with an unsaturated β-glucuronyl residue located at the non-reducing end. Exploration of the genomic environment around the Nonlabens ulvanivorans (previously Percicivirga ulvanivorans) ulvan lyase revealed a gene highly similar to known unsaturated uronyl hydrolases classified in the CAZy glycoside hydrolase family 105. The gene was cloned, the protein was overexpressed in Escherichia coli, and enzymology experiments demonstrated its unsaturated β-glucuronyl activity. Kinetic analysis of purified oligo-ulvans incubated with the new enzyme showed that the full substrate specificity is attained by three subsites that preferentially bind anionic residues (sulfated rhamnose, glucuronic/iduronic acid). The three-dimensional crystal structure of the native enzyme reveals that a trimeric organization is required for substrate binding and recognition at the +2 binding subsite. This novel unsaturated β-glucuronyl hydrolase is part of a previously uncharacterized subgroup of GH105 members and exhibits only a very limited sequence similarity to known unsaturated β-glucuronyl sequences previously found only in family GH88. Clan-O formed by families GH88 and GH105 was singular in the fact that it covered families acting on both axial and equatorial glycosidic linkages, respectively. The overall comparison of active site structures between enzymes from these two families highlights how that within family GH105, and unlike for classical glycoside hydrolysis, the hydrolysis of vinyl ether groups from unsaturated saccharides occurs independently of the α or β configuration of the cleaved linkage.},
keywords = {Biodegradation, crystal structure, Enzyme Catalysis, GH105, Glycoside Hydrolases, out_lab, Polysaccharide, Ulvan},
pubstate = {published},
tppubtype = {article}
}
@article{10.3389/fgene.2014.00241,
title = {Genome and metabolic network of “Candidatus Phaeomarinobacter ectocarpi” Ec32, a new candidate genus of Alphaproteobacteria frequently associated with brown algae},
author = {Simon M Dittami and Tristan Barbeyron and Catherine Boyen and Jeanne Cambefort and Guillaume Collet and Ludovic Delage and Angélique Gobet and Agnès Groisillier and Catherine Leblanc and Gurvan Michel and Delphine Scornet and Anne Siegel and Javier E Tapia and Thierry Tonon},
url = {https://www.frontiersin.org/article/10.3389/fgene.2014.00241},
doi = {10.3389/fgene.2014.00241},
issn = {1664-8021},
year  = {2014},
date = {2014-01-01},
journal = {Frontiers in Genetics},
volume = {5},
pages = {241},
abstract = {Rhizobiales and related orders of Alphaproteobacteria comprise several genera of nodule-inducing symbiotic bacteria associated with plant roots. Here we describe the genome and the metabolic network of “Candidatus Phaeomarinobacter ectocarpi” Ec32, a member of a new candidate genus closely related to Rhizobiales and found in association with cultures of the filamentous brown algal model Ectocarpus. The “Ca. P. ectocarpi” genome encodes numerous metabolic pathways that may be relevant for this bacterium to interact with algae. Notably, it possesses a large set of glycoside hydrolases and transporters, which may serve to process and assimilate algal metabolites. It also harbors several proteins likely to be involved in the synthesis of algal hormones such as auxins and cytokinins, as well as the vitamins pyridoxine, biotin, and thiamine. As of today, “Ca. P. ectocarpi” has not been successfully cultured, and identical 16S rDNA sequences have been found exclusively associated with Ectocarpus. However, related sequences (≥97% identity) have also been detected free-living and in a Fucus vesiculosus microbiome barcoding project, indicating that the candidate genus “Phaeomarinobacter” may comprise several species, which may colonize different niches.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{10.3389/fchem.2014.00067,
title = {Discovery of a novel iota carrageenan sulfatase isolated from the marine bacterium Pseudoalteromonas carrageenovora},
author = {Sabine M Genicot and Agnès Groisillier and Hélène Rogniaux and Laurence Meslet-Cladière and Tristan Barbeyron and William Helbert},
url = {https://www.frontiersin.org/article/10.3389/fchem.2014.00067},
doi = {10.3389/fchem.2014.00067},
issn = {2296-2646},
year  = {2014},
date = {2014-01-01},
journal = {Frontiers in Chemistry},
volume = {2},
pages = {67},
abstract = {Carrageenans are sulfated polysaccharides extracted from the cell wall of some marine red algae. These polysaccharides are widely used as gelling, stabilizing, and viscosifying agents in the food and pharmaceutical industries. Since the rheological properties of these polysaccharides depend on their sulfate content, we screened several isolated marine bacteria for carrageenan specific sulfatase activity, in the aim of developing enzymatic bioconversion of carrageenans. As a result of the screening, an iota-carrageenan sulfatase was detected in the cell-free lysate of the marine bacterium Pseudoalteromonas carrageenovora strain Psc^{T}. It was purified through Phenyl Sepharose and Diethylaminoethyl Sepharose chromatography. The pure enzyme, Psc ι-CgsA, was characterized. It had a molecular weight of 115.9 kDaltons and exhibited an optimal activity/stability at pH ~8.3 and at 40 ± 5°C. It was inactivated by phenylmethylsulfonyl fluoride but not by ethylene diamine tetraacetic acid. Psc ι-CgsA specifically catalyzes the hydrolysis of the 4-S sulfate of iota-carrageenan. The purified enzyme could transform iota-carrageenan into hybrid iota-/alpha- or pure alpha-carrageenan under controlled conditions. The gene encoding Psc ι-CgsA, a protein of 1038 amino acids, was cloned into Escherichia coli, and the sequence analysis revealed that Psc ι-CgsA has more than 90% sequence identity with a putative uncharacterized protein Q3IKL4 from the marine strain Pseudoalteromonas haloplanktis TAC 125, but besides this did not share any homology to characterized sulfatases. Phylogenetic studies show that P. carrageenovora sulfatase thus represents the first characterized member of a new sulfatase family, with a C-terminal domain having strong similarity with the superfamily of amidohydrolases, highlighting the still unexplored diversity of marine polysaccharide modifying enzymes.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@inproceedings{10.1007/978-3-319-07248-7_17,
title = {Automated Enzyme Classification by Formal Concept Analysis},
author = {François Coste and Gaëlle Garet and Agnès Groisillier and Jacques Nicolas and Thierry Tonon},
editor = {Cynthia Vera Glodeanu and Mehdi Kaytoue and Christian Sacarea},
doi = {10.1007/978-3-319-07248-7_17},
isbn = {978-3-319-07248-7},
year  = {2014},
date = {2014-01-01},
booktitle = {Formal Concept Analysis},
pages = {235--250},
publisher = {Springer International Publishing},
address = {Cham},
abstract = {Enzymes are macro-molecules (linear sequences of linked molecules) with a catalytic activity that make them essential for any biochemical reaction. High throughput genomic techniques give access to the sequence of new enzymes found in living organisms. Guessing the enzyme's functional activity from its sequence is a crucial task that can be approached by comparing the new sequences with those of already known enzymes labeled by a family class. This task is difficult because the activity is based on a combination of small sequence patterns and sequences greatly evolved over time. This paper presents a classifier based on the identification of common subsequence blocks between known and new enzymes and the search of formal concepts built on the cross product of blocks and sequences for each class. Since new enzyme families may emerge, it is important to propose a first classification of enzymes that cannot be assigned to a known family. FCA offers a nice framework to set the task as an optimization problem on the set of concepts. The classifier has been tested with success on a particular set of enzymes present in a large variety of species, the haloacid dehalogenase superfamily.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {inproceedings}
}
@article{NORMAND2014293,
title = {Identification and characterization of human Rad51 inhibitors by screening of an existing drug library},
author = {Anaïs Normand and Emmanuelle Rivière and Axelle Renodon-Cornière},
url = {https://www.sciencedirect.com/science/article/pii/S0006295214004547},
doi = {https://doi.org/10.1016/j.bcp.2014.07.033},
issn = {0006-2952},
year  = {2014},
date = {2014-01-01},
urldate = {2014-01-01},
journal = {Biochemical Pharmacology},
volume = {91},
number = {3},
pages = {293-300},
abstract = {Homologous Recombination (HR) plays an essential role in cellular proliferation and in maintaining genomic stability by repairing DNA double-stranded breaks that appear during replication. Rad51, a key protein of HR in eukaryotes, can have an elevated expression level in tumor cells, which correlates with their resistance to anticancer therapies. Therefore, targeted inhibition of Rad51 through inhibitor may improve the tumor response to these therapies. In order to identify small molecules that inhibit Rad51 activity, we screened the Prestwick Library (1120 molecules) for their effect on the strand exchange reaction catalyzed by Rad51. We found that Chicago Sky Blue (CSB) is a potent inhibitor of Rad51, showing IC50 values in the low nanomolar range (400nM). Biochemical analysis demonstrated that the inhibitory mechanism probably occurs by disrupting the Rad51 association with the single-stranded DNA, which prevents the nucleoprotein filament formation, the first step of the protein activity. Structure Activity Relationship analysis with a number of compounds that shared structure homology with CSB was also performed. The sensitivity of Rad51 inhibition to CSB modifications suggests specific interactions between the molecule and Rad51 nucleofilament. CSB and some of its analogs open up new perspectives in the search for agents capable of potentiating chemo- and radio-therapy treatments for cancer. Moreover, these compounds may be excellent tools to analyze Rad51 cellular functions. Our study also highlights how CSB and its analogs, which are frequently used in colorants, stains and markers, could be responsible of unwanted side effects by perturbing the DNA repair process.},
keywords = {Anticancer agent, Homologous Recombination, Inhibitor, Multidrug resistance, out_lab, Rad51},
pubstate = {published},
tppubtype = {article}
}
@article{teze2014semi,
title = {Semi-rational approach for converting a GH1 ß-glycosidase into a ß-transglycosidase},
author = {David Teze and Johann Hendrickx and Mirjam Czjzek and David Ropartz and Yves-Henri Sanejouand and Vinh Tran and Charles Tellier and Michel Dion},
doi = {10.1093/protein/gzt057},
year  = {2014},
date = {2014-01-01},
urldate = {2014-01-01},
journal = {Protein Engineering, Design & Selection},
volume = {27},
number = {1},
pages = {13--19},
publisher = {Oxford University Press},
abstract = {A large number of retaining glycosidases catalyze both hydrolysis and transglycosylation reactions, but little is known about what determines the balance between these two activities (transglycosylation/hydrolysis ratio). We previously obtained by directed evolution the mutants F401S and N282T of Thermus thermophilus β-glycosidase (Ttβ-gly, glycoside hydrolase family 1 (GH1)), which display a higher transglycosylation/hydrolysis ratio than the wild-type enzyme. In order to find the cause of these activity modifications, and thereby set up a generic method for easily obtaining transglycosidases from glycosidases, we determined their X-ray structure. No major structural changes could be observed which could help to rationalize the mutagenesis of glycosidases into transglycosidases. However, as these mutations are highly conserved in GH1 β-glycosidases and are located around the −1 site, we pursued the isolation of new transglycosidases by targeting highly conserved amino acids located around the active site. Thus, by single-point mutagenesis on Ttβ-gly, we created four new mutants that exhibit improved synthetic activity, producing disaccharides in yields of 68–90% against only 36% when native Ttβ-gly was used. As all of the chosen positions were well conserved among GH1 enzymes, this approach is most probably a general route to convert GH1 glycosidases into transglycosidases.},
keywords = {out_lab, team 1, team 2},
pubstate = {published},
tppubtype = {article}
}
@article{pmid23915294,
title = {A high-throughput seed germination assay for root parasitic plants},
author = {Jean-Bernard Pouvreau and Zachary Gaudin and Bathilde Auger and Marc-Marie Lechat and Mathieu Gauthier and Philippe Delavault and Philippe Simier},
doi = {10.1186/1746-4811-9-32},
issn = {1746-4811},
year  = {2013},
date = {2013-08-01},
urldate = {2013-08-01},
journal = {Plant Methods},
volume = {9},
number = {1},
pages = {32},
abstract = {BACKGROUND: Some root-parasitic plants belonging to the Orobanche, Phelipanche or Striga genus represent one of the most destructive and intractable weed problems to agricultural production in both developed and developing countries. Compared with most of the other weeds, parasitic weeds are difficult to control by conventional methods because of their life style. The main difficulties that currently limit the development of successful control methods are the ability of the parasite to produce a tremendous number of tiny seeds that may remain viable in the soil for more than 15 years. Seed germination requires induction by stimulants present in root exudates of host plants. Researches performed on these minute seeds are until now tedious and time-consuming because germination rate is usually evaluated in Petri-dish by counting germinated seeds under a binocular microscope.

RESULTS: We developed an easy and fast method for germination rate determination based on a standardized 96-well plate test coupled with spectrophotometric reading of tetrazolium salt (MTT) reduction. We adapted the Mosmann&#039;s protocol for cell cultures to germinating seeds and determined the conditions of seed stimulation and germination, MTT staining and formazan salt solubilization required to obtain a linear relationship between absorbance and germination rate. Dose-response analyses were presented as applications of interest for assessing half maximal effective or inhibitory concentrations of germination stimulants (strigolactones) or inhibitors (ABA), respectively, using four parameter logistic curves.

CONCLUSION: The developed MTT system is simple and accurate. It yields reproducible results for germination bioassays of parasitic plant seeds. This method is adapted to high-throughput screenings of allelochemicals (stimulants, inhibitors) or biological extracts on parasitic plant seed germination, and strengthens the investigations of distinctive features of parasitic plant germination.},
keywords = {out_lab, team 4},
pubstate = {published},
tppubtype = {article}
}
@article{Manoharan:2013ab,
title = {Comparative genomics of odorant binding proteins in Anopheles gambiae, Aedes aegypti, and Culex quinquefasciatus},
author = {Malini Manoharan and Matthieu Ng Fuk Chong and Aurore Vaïtinadapoulé and Etienne Frumence and Ramanathan Sowdhamini and Bernard Offmann},
doi = {10.1093/gbe/evs131},
year  = {2013},
date = {2013-01-01},
journal = {Genome Biol Evol},
volume = {5},
number = {1},
pages = {163-80},
abstract = {About 1 million people in the world die each year from diseases spread by mosquitoes, and understanding the mechanism of host identification by the mosquitoes through olfaction is at stake. The role of odorant binding proteins (OBPs) in the primary molecular events of olfaction in mosquitoes is becoming an important focus of biological research in this area. Here, we present a comprehensive comparative genomics study of OBPs in the three disease-transmitting mosquito species Anopheles gambiae, Aedes aegypti, and Culex quinquefasciatus starting with the identification of 110 new OBPs in these three genomes. We have characterized their genomic distribution and orthologous and phylogenetic relationships. The diversity and expansion observed with respect to the Aedes and Culex genomes suggests that the OBP gene family acquired functional diversity concurrently with functional constraints posed on these two species. Sequences with unique features have been characterized such as the "two-domain OBPs" (previously known as Atypical OBPs) and "MinusC OBPs" in mosquito genomes. The extensive comparative genomics featured in this work hence provides useful primary insights into the role of OBPs in the molecular adaptations of mosquito olfactory system and could provide more clues for the identification of potential targets for insect repellants and attractants.},
keywords = {out_lab, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{Mahajan:2013aa,
title = {DoSA: Database of Structural Alignments},
author = {Swapnil Mahajan and Garima Agarwal and Mohammed Iftekhar and Bernard Offmann and Alexandre G {de Brevern} and Narayanaswamy Srinivasan},
doi = {10.1093/database/bat048},
year  = {2013},
date = {2013-01-01},
journal = {Database (Oxford)},
volume = {2013},
pages = {bat048},
abstract = {Protein structure alignment is a crucial step in protein structure-function analysis. Despite the advances in protein structure alignment algorithms, some of the local conformationally similar regions are mislabeled as structurally variable regions (SVRs). These regions are not well superimposed because of differences in their spatial orientations. The Database of Structural Alignments (DoSA) addresses this gap in identification of local structural similarities obscured in global protein structural alignments by realigning SVRs using an algorithm based on protein blocks. A set of protein blocks is a structural alphabet that abstracts protein structures into 16 unique local structural motifs. DoSA provides unique information about 159,780 conformationally similar and 56,140 conformationally dissimilar SVRs in 74 705 pairwise structural alignments of homologous proteins. The information provided on conformationally similar and dissimilar SVRs can be helpful to model loop regions. It is also conceivable that conformationally similar SVRs with conserved residues could potentially contribute toward functional integrity of homologues, and hence identifying such SVRs could be helpful in understanding the structural basis of protein function. Database URL: http://bo-protscience.fr/dosa/},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Manoharan:2013aa,
title = {Association of putative members to family of mosquito odorant binding proteins: scoring scheme using fuzzy functional templates and cys residue positions},
author = {Malini Manoharan and Kannan Sankar and Bernard Offmann and Sowdhamini Ramanathan},
doi = {10.4137/BBI.S11096},
year  = {2013},
date = {2013-01-01},
journal = {Bioinform Biol Insights},
volume = {7},
pages = {231-51},
abstract = {Proteins may be related to each other very specifically as homologous subfamilies. Proteins can also be related to diverse proteins at the super family level. It has become highly important to characterize the existing sequence databases by their signatures to facilitate the function annotation of newly added sequences. The algorithm described here uses a scheme for the classification of odorant binding proteins on the basis of functional residues and Cys-pairing. The cysteine-based scoring scheme not only helps in unambiguously identifying families like odorant binding proteins (OBPs), but also aids in their classification at the subfamily level with reliable accuracy. The algorithm was also applied to yet another cysteine-rich family, where similar accuracy was observed that ensures the application of the protocol to other families.},
keywords = {out_lab, team 1},
pubstate = {published},
tppubtype = {article}
}
@article{DELAVAT2013823,
title = {Yeast and bacterial diversity along a transect in an acidic, As–Fe rich environment revealed by cultural approaches},
author = {François Delavat and Marie-Claire Lett and Didier Lièvremont},
url = {https://www.sciencedirect.com/science/article/pii/S004896971300675X},
doi = {https://doi.org/10.1016/j.scitotenv.2013.06.023},
issn = {0048-9697},
year  = {2013},
date = {2013-01-01},
journal = {Science of The Total Environment},
volume = {463-464},
pages = {823-828},
abstract = {Acid mine drainages (AMDs) are often thought to harbour low biodiversity, yet little is known about the diversity distribution along the drainages. Using culture-dependent approaches, the microbial diversity from the Carnoulès AMD sediment was investigated for the first time along a transect showing progressive environmental stringency decrease. In total, 20 bacterial genera were detected, highlighting a higher bacterial diversity than previously thought. Moreover, this approach led to the discovery of 16 yeast species, demonstrating for the first time the presence of this important phylogenetic group in this AMD. All in all, the location of the microbes along the transect helps to better understand their distribution in a pollution gradient.},
keywords = {Acid mine drainage (AMD), Carnoulès, Culture, Microbial diversity, out_lab, Yeasts},
pubstate = {published},
tppubtype = {article}
}
@article{Hyams354,
title = {Streptococcus pneumoniae Capsular Serotype Invasiveness Correlates with the Degree of Factor H Binding and Opsonization with C3b/iC3b},
author = {Catherine Hyams and Krzysztof Trzcinski and Emilie Camberlein and Daniel M Weinberger and Suneeta Chimalapati and Mahdad Noursadeghi and Marc Lipsitch and Jeremy S Brown},
editor = {A Camilli},
url = {https://iai.asm.org/content/81/1/354},
doi = {10.1128/IAI.00862-12},
issn = {0019-9567},
year  = {2013},
date = {2013-01-01},
journal = {Infection and Immunity},
volume = {81},
number = {1},
pages = {354--363},
publisher = {American Society for Microbiology Journals},
abstract = {Different capsular serotypes of Streptococcus pneumoniae vary markedly in their ability to cause invasive infection, but the reasons why are not known. As immunity to S. pneumoniae infection is highly complement dependent, variations in sensitivity to complement between S. pneumoniae capsular serotypes could affect invasiveness. We have used 20 capsule-switched variants of strain TIGR4 to investigate whether differences in the binding of the alternative pathway inhibitor factor H (FH) could be one mechanism causing variations in complement resistance and invasive potential between capsular serotypes. Flow cytometry assays were used to assess complement factor binding and complement-dependent neutrophil association for the TIGR4 capsule-switched strains. FH binding varied with the serotype and inversely correlated with the results of factor B binding, C3b/iC3b deposition, and neutrophil association. Differences between strains in FH binding were lost when assays were repeated with pspC mutant strains, and loss of PspC also reduced differences in C3b/iC3b deposition between strains. Median FH binding was high in capsule-switched mutant strains expressing more invasive serotypes, and a principal component analysis demonstrated a strong correlation between serotype invasiveness, high FH binding, and resistance to complement and neutrophil association. Further data obtained with 33 clinical strains also demonstrated that FH binding negatively correlated with C3b/iC3b deposition and that median FH binding was high in strains expressing more invasive serotypes. These data suggest that variations in complement resistance between S. pneumoniae strains and the association of a serotype with invasiveness could be related to capsular serotype effects on FH binding.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{10.1093/jxb/ert405,
title = {Mannitol metabolism in brown algae involves a new phosphatase family},
author = {Agnès Groisillier and Zhanru Shao and Gurvan Michel and Sophie Goulitquer and Patricia Bonin and Stefan Krahulec and Bernd Nidetzky and Delin Duan and Catherine Boyen and Thierry Tonon},
url = {https://doi.org/10.1093/jxb/ert405},
doi = {10.1093/jxb/ert405},
issn = {0022-0957},
year  = {2013},
date = {2013-01-01},
journal = {Journal of Experimental Botany},
volume = {65},
number = {2},
pages = {559-570},
abstract = {Brown algae belong to a phylogenetic lineage distantly related to green plants and animals, and are found predominantly in the intertidal zone, a harsh and frequently changing environment. Because of their unique evolutionary history and of their habitat, brown algae feature several peculiarities in their metabolism. One of these is the mannitol cycle, which plays a central role in their physiology, as mannitol acts as carbon storage, osmoprotectant, and antioxidant. This polyol is derived directly from the photoassimilate fructose-6-phosphate via the action of a mannitol-1-phosphate dehydrogenase and a mannitol-1-phosphatase (M1Pase). Genome analysis of the brown algal model Ectocarpus siliculosus allowed identification of genes potentially involved in the mannitol cycle. Among these, two genes coding for haloacid dehalogenase (HAD)-like enzymes were suggested to correspond to M1Pase activity, and thus were named EsM1Pase1 and EsM1Pase2, respectively. To test this hypothesis, both genes were expressed in Escherichia coli. Recombinant EsM1Pase2 was shown to hydrolyse the phosphate group from mannitol-1-phosphate to produce mannitol but was not active on the hexose monophosphates tested. Gene expression analysis showed that transcription of both E. siliculosus genes was under the influence of the diurnal cycle. Sequence analysis and three-dimensional homology modelling indicated that EsM1Pases, and their orthologues in Prasinophytes, should be seen as founding members of a new family of phosphatase with original substrate specificity within the HAD superfamily of proteins. This is the first report describing the characterization of a gene encoding M1Pase activity in photosynthetic organisms.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Collén5247,
title = {Genome structure and metabolic features in the red seaweed Chondrus crispus shed light on evolution of the Archaeplastida},
author = {Jonas Collén and Betina Porcel and Wilfrid Carré and Steven G Ball and Cristian Chaparro and Thierry Tonon and Tristan Barbeyron and Gurvan Michel and Benjamin Noel and Klaus Valentin and Marek Elias and François Artiguenave and Alok Arun and Jean-Marc Aury and José F Barbosa-Neto and John H Bothwell and François-Yves Bouget and Loraine Brillet and Francisco Cabello-Hurtado and Salvador Capella-Gutiérrez and Bénédicte Charrier and Lionel Cladière and Mark J Cock and Susana M Coelho and Christophe Colleoni and Mirjam Czjzek and Corinne Da Silva and Ludovic Delage and France Denoeud and Philippe Deschamps and Simon M Dittami and Toni Gabaldón and Claire M M Gachon and Agnès Groisillier and Cécile Hervé and Kamel Jabbari and Michael Katinka and Bernard Kloareg and Nathalie Kowalczyk and Karine Labadie and Catherine Leblanc and Pascal J Lopez and Deirdre H McLachlan and Laurence Meslet-Cladiere and Ahmed Moustafa and Zofia Nehr and Pi Nyvall Collén and Olivier Panaud and Frédéric Partensky and Julie Poulain and Stefan A Rensing and Sylvie Rousvoal and Gaelle Samson and Aikaterini Symeonidi and Jean Weissenbach and Antonios Zambounis and Patrick Wincker and Catherine Boyen},
url = {https://www.pnas.org/content/110/13/5247},
doi = {10.1073/pnas.1221259110},
issn = {0027-8424},
year  = {2013},
date = {2013-01-01},
journal = {Proceedings of the National Academy of Sciences},
volume = {110},
number = {13},
pages = {5247--5252},
publisher = {National Academy of Sciences},
abstract = {Red seaweeds are key components of coastal ecosystems and are economically important as food and as a source of gelling agents, but their genes and genomes have received little attention. Here we report the sequencing of the 105-Mbp genome of the florideophyte Chondrus crispus (Irish moss) and the annotation of the 9,606 genes. The genome features an unusual structure characterized by gene-dense regions surrounded by repeat-rich regions dominated by transposable elements. Despite its fairly large size, this genome shows features typical of compact genomes, e.g., on average only 0.3 introns per gene, short introns, low median distance between genes, small gene families, and no indication of large-scale genome duplication. The genome also gives insights into the metabolism of marine red algae and adaptations to the marine environment, including genes related to halogen metabolism, oxylipins, and multicellularity (microRNA processing and transcription factors). Particularly interesting are features related to carbohydrate metabolism, which include a minimalistic gene set for starch biosynthesis, the presence of cellulose synthases acquired before the primary endosymbiosis showing the polyphyly of cellulose synthesis in Archaeplastida, and cellulases absent in terrestrial plants as well as the occurrence of a mannosylglycerate synthase potentially originating from a marine bacterium. To explain the observations on genome structure and gene content, we propose an evolutionary scenario involving an ancestral red alga that was driven by early ecological forces to lose genes, introns, and intergenetic DNA; this loss was followed by an expansion of genome size as a consequence of activity of transposable elements.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid22859674,
title = {PrCYP707A1, an ABA catabolic gene, is a key component of Phelipanche ramosa seed germination in response to the strigolactone analogue GR24},
author = {Marc-Marie Lechat and Jean-Bernard Pouvreau and Thomas Péron and Mathieu Gauthier and Grégory Montiel and Christophe Véronési and Yasushi Todoroki and Bruno Le Bizec and Fabrice Monteau and David Macherel and Philippe Simier and Séverine Thoiron and Philippe Delavault},
doi = {10.1093/jxb/ers189},
issn = {1460-2431},
year  = {2012},
date = {2012-09-01},
urldate = {2012-09-01},
journal = {J Exp Bot},
volume = {63},
number = {14},
pages = {5311--5322},
abstract = {After a conditioning period, seed dormancy in obligate root parasitic plants is released by a chemical stimulus secreted by the roots of host plants. Using Phelipanche ramosa as the model, experiments conducted in this study showed that seeds require a conditioning period of at least 4 d to be receptive to the synthetic germination stimulant GR24. A cDNA-AFLP procedure on seeds revealed 58 transcript-derived fragments (TDFs) whose expression pattern changed upon GR24 treatment. Among the isolated TDFs, two up-regulated sequences corresponded to an abscisic acid (ABA) catabolic gene, PrCYP707A1, encoding an ABA 8&#039;-hydroxylase. Using the rapid amplification of cDNA ends method, two full-length cDNAs, PrCYP707A1 and PrCYP707A2, were isolated from seeds. Both genes were always expressed at low levels during conditioning during which an initial decline in ABA levels was recorded. GR24 application after conditioning triggered a strong up-regulation of PrCYP707A1 during the first 18 h, followed by an 8-fold decrease in ABA levels detectable 3 d after treatment. In situ hybridization experiments on GR24-treated seeds revealed a specific PrCYP707A1 mRNA accumulation in the cells located between the embryo and the micropyle. Abz-E2B, a specific inhibitor of CYP707A enzymes, significantly impeded seed germination, proving to be a non-competitive antagonist of GR24 with reversible inhibitory activity. These results demonstrate that P. ramosa seed dormancy release relies on ABA catabolism mediated by the GR24-dependent activation of PrCYP707A1. In addition, in situ hybridization corroborates the putative location of cells receptive to the germination stimulants in seeds.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid22723084,
title = {Structure-activity relationship studies of strigolactone-related molecules for branching inhibition in garden pea: molecule design for shoot branching},
author = {François-Didier Boyer and Alexandre de Saint Germain and Jean-Paul Pillot and Jean-Bernard Pouvreau and Victor Xiao Chen and Suzanne Ramos and Arnaud Stévenin and Philippe Simier and Philippe Delavault and Jean-Marie Beau and Catherine Rameau},
doi = {10.1104/pp.112.195826},
issn = {1532-2548},
year  = {2012},
date = {2012-08-01},
urldate = {2012-08-01},
journal = {Plant Physiol},
volume = {159},
number = {4},
pages = {1524--1544},
abstract = {Initially known for their role in the rhizosphere in stimulating the seed germination of parasitic weeds such as the Striga and Orobanche species, and later as host recognition signals for arbuscular mycorrhizal fungi, strigolactones (SLs) were recently rediscovered as a new class of plant hormones involved in the control of shoot branching in plants. Herein, we report the synthesis of new SL analogs and, to our knowledge, the first study of SL structure-activity relationships for their hormonal activity in garden pea (Pisum sativum). Comparisons with their action for the germination of broomrape (Phelipanche ramosa) are also presented. The pea rms1 SL-deficient mutant was used in a SL bioassay based on axillary bud length after direct SL application on the bud. This assay was compared with an assay where SLs were fed via the roots using hydroponics and with a molecular assay in which transcript levels of BRANCHED1, the pea homolog of the maize TEOSINTE BRANCHED1 gene were quantified in axillary buds only 6 h after application of SLs. We have demonstrated that the presence of a Michael acceptor and a methylbutenolide or dimethylbutenolide motif in the same molecule is essential. It was established that the more active analog 23 with a dimethylbutenolide as the D-ring could be used to control the plant architecture without strongly favoring the germination of P. ramosa seeds. Bold numerals refer to numbers of compounds.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid22414435,
title = {Germination stimulants of Phelipanche ramosa in the rhizosphere of Brassica napus are derived from the glucosinolate pathway},
author = {Bathilde Auger and Jean-Bernard Pouvreau and Karinne Pouponneau and Kaori Yoneyama and Grégory Montiel and Bruno Le Bizec and Koichi Yoneyama and Philippe Delavault and Régine Delourme and Philippe Simier},
doi = {10.1094/MPMI-01-12-0006-R},
issn = {0894-0282},
year  = {2012},
date = {2012-07-01},
urldate = {2012-07-01},
journal = {Mol Plant Microbe Interact},
volume = {25},
number = {7},
pages = {993--1004},
abstract = {Phelipanche ramosa is a major parasitic weed of Brassica napus. The first step in a host-parasitic plant interaction is stimulation of parasite seed germination by compounds released from host roots. However, germination stimulants produced by B. napus have not been identified yet. In this study, we characterized the germination stimulants that accumulate in B. napus roots and are released into the rhizosphere. Eight glucosinolate-breakdown products were identified and quantified in B. napus roots by gas chromatography-mass spectrometry. Two (3-phenylpropanenitrile and 2-phenylethyl isothiocyanate [2-PEITC]) were identified in the B. napus rhizosphere. Among glucosinolate-breakdown products, P. ramosa germination was strongly and specifically triggered by isothiocyanates, indicating that 2-PEITC, in particular, plays a key role in the B. napus-P. ramosa interaction. Known strigolactones were not detected by ultraperformance liquid chromatography-tandem mass spectrometry, and seed of Phelipanche and Orobanche spp. that respond to strigolactones but not to isothiocyanates did not germinate in the rhizosphere of B. napus. Furthermore, both wild-type and strigolactone biosynthesis mutants of Arabidopsis thaliana Atccd7 and Atccd8 induced similar levels of P. ramosa seed germination, suggesting that compounds other than strigolactone function as germination stimulants for P. ramosa in other Brassicaceae spp. Our results open perspectives on the high adaptation potential of root-parasitic plants under host-driven selection pressures.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid22423636,
title = {Biological activities of purified marennine, the blue pigment responsible for the greening of oysters},
author = {Romain Gastineau and Jean-Bernard Pouvreau and Claire Hellio and Michele Morançais and Joël Fleurence and Pierre Gaudin and Nathalie Bourgougnon and Jean-Luc Mouget},
doi = {10.1021/jf205004x},
issn = {1520-5118},
year  = {2012},
date = {2012-04-01},
urldate = {2012-04-01},
journal = {J Agric Food Chem},
volume = {60},
number = {14},
pages = {3599--3605},
abstract = {Marennine, the blue pigment produced by the diatom Haslea ostrearia , exists in two different forms, the intra- and extracellular forms. We investigated the antibacterial, antiviral, and antiproliferative properties of both of these forms. Both forms of marennine inhibited the development of marine bacteria, in particular the pathogenic organism Vibrio aesturianus , at concentrations as low as 1 μg/mL, but they did not display any effect on a wide range of pathogenic bacteria that are relevant for food safety. Both forms of the pigment produced by H. ostrearia also exhibited antiviral activity against the HSV1 herpes virus, with intra- and extracellular marennine having EC(50) values of 24.0 and 27.0 μg/mL, respectively. These values are 2 orders of magnitude higher than the value for the reference drug, Zovirax. Moreover, both forms of marennine were effective in slowing or inhibiting the proliferation of cancer cells. This study confirms the potential of marennine as a biologically active organic molecule, which could have a protective effect on bivalves, which filter seawater and fix the pigment on their gills. Moreover, marennine could be used in food engineering and chemistry as a natural blue pigment. However, despite that it is eaten and possibly assimilated by green oyster consumers, it also deserves in depth evaluation before being considered for use as a nutraceutical.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid22088196,
title = {Role of the sucrose synthase encoding PrSus1 gene in the development of the parasitic plant Phelipanche ramosa L. (Pomel)},
author = {Thomas Péron and Christophe Véronési and Eric Mortreau and Jean-Bernard Pouvreau and Séverine Thoiron and Nathalie Leduc and Philippe Delavault and Philippe Simier},
doi = {10.1094/MPMI-10-11-0260},
issn = {0894-0282},
year  = {2012},
date = {2012-03-01},
urldate = {2012-03-01},
journal = {Mol Plant Microbe Interact},
volume = {25},
number = {3},
pages = {402--411},
abstract = {Phelipanche ramosa L. (Pomel) is a major root-parasitic weed attacking many important crops. Success in controlling this parasite is rare and a better understanding of its unique biology is needed to develop new specific control strategies. In the present study, quantitative polymerase chain reaction experiments showed that sucrose synthase encoding PrSus1 transcripts accumulate at their highest level once the parasite is connected to the host (tomato) vascular system, mainly in the parasite tubercles, which bear numerous adventitious roots. In situ hybridization experiments revealed strong PrSus1 expression in both shoot and root apices, especially in shoot apical meristems and in the vascular tissues of scale leaves and stems, and in the apical meristems and developing xylem in roots. In addition, immunolocalization experiments showed that a sucrose synthase protein co-localized with cell-wall thickening in xylem elements. These findings highlight the role of PrSus1 in the utilization of host-derived sucrose in meristematic areas and in cellulose biosynthesis in differentiating vascular elements. We also demonstrate that PrSus1 is downregulated in response to 2,3,5-triiodobenzoic acid-induced inhibition of polar auxin transport in the host stem, suggesting that PrSus1 activity in xylem maturation is controlled by host-derived auxin.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@inbook{Delavat2012remediation,
title = {Remediation using arsenite­ oxidizing bacteria},
author = {François Delavat and Marie-Claire Lett and Didier Lièvremont},
editor = {J.M. Santini and S.A. Ward},
url = {https://tel.archives-ouvertes.fr/tel-00797981/document#page=194},
isbn = {9780415697194},
year  = {2012},
date = {2012-01-01},
volume = {5},
edition = {CRC Press},
chapter = {11},
keywords = {out_lab},
pubstate = {published},
tppubtype = {inbook}
}
@article{delavat2012amylases,
title = {Amylases without known homologues discovered in an acid mine drainage: significance and impact},
author = {François Delavat and Vincent Phalip and Anne Forster and Frédéric Plewniak and Marie-Claire Lett and Didier Lievremont},
url = {https://doi.org/10.1038/srep00354},
doi = {https://doi.org/10.1038/srep00354},
year  = {2012},
date = {2012-01-01},
journal = {Scientific Reports},
volume = {2},
number = {1},
pages = {1--6},
publisher = {Nature Publishing Group},
abstract = {Acid Mine Drainages (AMDs) are extreme environments characterized by acidic and oligotrophic conditions and by metal contaminations. A function-based screening of an AMD-derived metagenomic library led to the discovery and partial characterization of two non-homologous endo-acting amylases sharing no sequence similarity with any known amylase nor glycosidase. None carried known amylolytic domains, nor could be assigned to any GH-family. One amylase displayed no similarity with any known protein, whereas the second one was similar to TraC proteins involved in the bacterial type IV secretion system. According to the scarce similarities with known proteins, 3D-structure modelling using I-TASSER was unsuccessful. This study underlined the utility of a function-driven metagenomic approach to obtain a clearer image of the bacterial community enzymatic landscape. More generally, this work points out that screening for microorganisms or biomolecules in a priori incongruous environments could provide unconventional and new exciting ways for bioprospecting.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{delavat2012deciphering,
title = {Deciphering the role of Paenibacillus strain Q8 in the organic matter recycling in the acid mine drainage of Carnoules},
author = {François Delavat and Vincent Phalip and Anne Forster and Marie-Claire Lett and Didier Lièvremont},
url = {https://doi.org/10.1186/1475-2859-11-16},
doi = {https://doi.org/10.1186/1475-2859-11-16},
year  = {2012},
date = {2012-01-01},
journal = {Microbial cell factories},
volume = {11},
number = {1},
pages = {1--10},
abstract = {BACKGROUD. The recycling of the organic matter is a crucial function in any environment, especially in oligotrophic environments such as Acid Mine Drainages (AMDs). Polymer-degrading bacteria might play an important role in such ecosystem, at least by releasing by-products useful for the rest of the community. In this study, physiological, molecular and biochemical experiments were performed to decipher the role of a Paenibacillus strain isolated from the sediment of Carnoulès AMD. 
 RESULTS. Even though Paenibacillus sp. strain Q8 was isolated from an oligotrophic AMD showing an acidic pH, it developed under both acidic and alkaline conditions and showed a heterotrophic metabolism based on the utilization of a broad range of organic compounds. It resisted to numerous metallic stresses, particularly high arsenite (As(III)) concentrations (&gt; 1,800 mg/L). Q8 was also able to efficiently degrade polymers such as cellulose, xylan and starch. Function-based screening of a Q8 DNA-library allowed the detection of 15 clones with starch-degrading activity and 3 clones with xylan-degrading activity. One clone positive for starch degradation carried a single gene encoding a "protein of unknown function". Amylolytic and xylanolytic activities were measured both in growing cells and with acellular extracts of Q8. The results showed the ability of Q8 to degrade both polymers under a broad pH range and high As(III) and As(V) concentrations. Activity measurements allowed to point out the constitutive expression of the amylase genes and the mainly inducible expression of the xylanase genes. PACE demonstrated the endo-acting activity of the amylases and the exo-acting activity of the xylanases. 
 CONCLUSIONS. AMDs have been studied for years especially with regard to interactions between bacteria and the inorganic compartment hosting them. To date, no study reported the role of microorganisms in the recycling of the organic matter. The present work suggests that the strain Q8 might play an important role in the community by recycling the scarce organic matter (cellulose, hemicellulose, starch...), especially when the conditions change. Furthermore, function-based screening of a Q8 DNA library allowed to assign an amylolytic function to a gene previously unknown. AMDs could be considered as a reservoir of genes with potential biotechnological properties.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{delavat2012novel,
title = {Novel and unexpected bacterial diversity in an arsenic-rich ecosystem revealed by culture-dependent approaches},
author = {François Delavat and Marie-Claire Lett and Didier Lièvremont},
url = {https://doi.org/10.1186/1745-6150-7-28},
doi = {https://doi.org/10.1186/1745-6150-7-28},
year  = {2012},
date = {2012-01-01},
journal = {Biology Direct},
volume = {7},
number = {1},
pages = {1--14},
publisher = {BioMed Central},
abstract = {BACKGROUND 
Acid Mine Drainages (AMDs) are extreme environments characterized by very acid conditions and heavy metal contaminations. In these ecosystems, the bacterial diversity is considered to be low. Previous culture-independent approaches performed in the AMD of Carnoulès (France) confirmed this low species richness. However, very little is known about the cultured bacteria in this ecosystem. The aims of the study were firstly to apply novel culture methods in order to access to the largest cultured bacterial diversity, and secondly to better define the robustness of the community for 3 important functions: As(III) oxidation, cellulose degradation and cobalamine biosynthesis. 
 
RESULTS 
Despite the oligotrophic and acidic conditions found in AMDs, the newly designed media covered a large range of nutrient concentrations and a pH range from 3.5 to 9.8, in order to target also non-acidophilic bacteria. These approaches generated 49 isolates representing 19 genera belonging to 4 different phyla. Importantly, overall diversity gained 16 extra genera never detected in Carnoulès. Among the 19 genera, 3 were previously uncultured, one of them being novel in databases. This strategy increased the overall diversity in the Carnoulès sediment by 70% when compared with previous culture-independent approaches, as specific phylogenetic groups (e.g. the subclass Actinobacteridae or the order Rhizobiales) were only detected by culture. Cobalamin auxotrophy, cellulose degradation and As(III)-oxidation are 3 crucial functions in this ecosystem, and a previous meta- and proteo-genomic work attributed each function to only one taxon. Here, we demonstrate that other members of this community can also assume these functions, thus increasing the overall community robustness. 
 
CONCLUSIONS 
This work highlights that bacterial diversity in AMDs is much higher than previously envisaged, thus pointing out that the AMD system is functionally more robust than expected. The isolated bacteria may be part of the rare biosphere which remained previously undetected due to molecular biases. No matter their current ecological relevance, the exploration of the full diversity remains crucial to decipher the function and dynamic of any community. This work also underlines the importance to associate culture-dependent and -independent approaches to gain an integrative view of the community function.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{chimalapati2012effects,
title = {Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo},
author = {Suneeta Chimalapati and Jonathan M Cohen and Emilie Camberlein and Nathanael MacDonald and Claire Durmort and Thierry Vernet and Peter WM Hermans and Timothy Mitchell and Jeremy S Brown},
doi = {10.1371/journal.pone.0041393},
year  = {2012},
date = {2012-01-01},
journal = {PLoS One},
volume = {7},
number = {7},
pages = {e41393},
publisher = {Public Library of Science},
abstract = {Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pavitra2012genetic,
title = {Genetic diversity of Bradyrhizobia isolated from vegetable soybean (Glycine max L.) genotypes.},
author = {BV Pavitra and Ashish K Shanbhogue and Iyanar Vetrivel and N Earanna},
url = {https://www.researchgate.net/profile/Iyanar_Vetrivel/publication/332275822_Genetic_Diversity_of_Bradyrhizobia_Isolated_from_Vegetable_Soybean_Glycine_max_L_Genotypes/links/5cab6e59299bf118c4bae7a0/Genetic-Diversity-of-Bradyrhizobia-Isolated-from-Vegetable-Soybean-Glycine-max-L-Genotypes.pdf},
year  = {2012},
date = {2012-01-01},
journal = {Environment and Ecology},
volume = {30},
number = {3A},
pages = {726--730},
publisher = {MKK Publication},
abstract = {Bradyrhizobia associated with 12 different vegetable soybean genotypes were isolated and characterized. Genetic diversity of these isolates were analyzed using randomly amplified plymorhic DNA (RAPD) primers in PCR. The 10 random primers produced total of 89 amplified products of which 59 were found polymorphic. The 12 strains formed 2 major clusters and three sub clusters. The strains VSBR-1, 2 and 3 formed one cluster. The strains VSBR-4, 6, and 12 formed the second cluster and the third cluster was with the strains VSBR-5, 7, 8, 10, 9, and 11. This indicated the diversity between the bradyrhizobial strains isolated from 12 different soybean genotypes.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid21726369,
title = {Invertases involved in the development of the parasitic plant Phelipanche ramosa: characterization of the dominant soluble acid isoform, PrSAI1},
author = {Rida Draie and Thomas Péron and Jean-Bernard Pouvreau and Christophe Véronési and Sandrine Jégou and Philippe Delavault and Séverine Thoiron and Philippe Simier},
doi = {10.1111/j.1364-3703.2010.00702.x},
issn = {1364-3703},
year  = {2011},
date = {2011-09-01},
urldate = {2011-09-01},
journal = {Mol Plant Pathol},
volume = {12},
number = {7},
pages = {638--652},
abstract = {Phelipanche ramosa L. parasitizes major crops, acting as a competitive sink for host photoassimilates, especially sucrose. An understanding of the mechanisms of sucrose utilization in parasites is an important step in the development of new control methods. Therefore, in this study, we characterized the invertase gene family in P. ramosa and analysed its involvement in plant development. Invertase-encoded cDNAs were isolated using degenerate primers corresponding to highly conserved regions of invertases. In addition to enzyme assays, gene expression was analysed using real-time quantitative reverse transcriptase-polymerase chain reaction during overall plant development. The dominant isoform was purified and sequenced using electrospray ionization-liquid chromatography-tandem mass spectrometry (ESI-LC-MS/MS). Five invertase-encoded cDNAs were thus characterized, including PrSai1 which encodes a soluble acid invertase (SAI). Of the five invertases, PrSai1 transcripts and SAI activity were dominant in growing organs. The most active invertase corresponded to the PrSai1 gene product. The purified PrSAI1 displayed low pI and optimal pH values, specificity for β-fructofuranosides and inhibition by metallic ions and competitive inhibition by fructose. PrSAI1 is a typical vacuolar SAI that is actively involved in growth following both germination and attachment to host roots. In addition, germinated seeds displayed enhanced cell wall invertase activity (PrCWI) in comparison with preconditioned seeds, suggesting the contribution of this activity in the sink strength of infected roots during the subsequent step of root penetration. Our results show that PrSAI1 and, possibly, PrCWI constitute good targets for the development of new transgenic resistance in host plants using proteinaceous inhibitors or silencing strategies.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Chilamakuri:2011aa,
title = {Cross-Genome Comparisons of Newly Identified Domains in Mycoplasma gallisepticum and Domain Architectures with Other Mycoplasma species},
author = {Chandra Sekhar Reddy Chilamakuri and Adwait Joshi and Sane Sudha Rani and Bernard Offmann and R Sowdhamini},
doi = {10.1155/2011/878973},
year  = {2011},
date = {2011-01-01},
journal = {Comparative and Functional Genomics},
volume = {2011},
abstract = {Accurate functional annotation of protein sequences is hampered by important factors such as the failure of sequence search methods to identify relationships and the inherent diversity in function of proteins related at low sequence similarities. Earlier, we had employed intermediate sequence search approach to establish new domain relationships in the unassigned regions of gene products at the whole genome level by taking Mycoplasma gallisepticum as a specific example and established new domain relationships. In this paper, we report a detailed comparison of the conservation status of the domain and domain architectures of the gene products that bear our newly predicted domains amongst 14 other Mycoplasma genomes and reported the probable implications for the organisms. Some of the domain associations, observed in Mycoplasma that afflict humans and other non-human primates, are involved in regulation of solute transport and DNA binding suggesting specific modes of host-pathogen interactions.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Joseph:2010aa,
title = {A short survey on protein blocks},
author = {Agnel Praveen Joseph and Garima Agarwal and Swapnil Mahajan and Jean-Christophe Gelly and Lakshmipuram S Swapna and Bernard Offmann and Frédéric Cadet and Aurélie Bornot and Manoj Tyagi and Hélène Valadié and Bohdan Schneider and Catherine Etchebest and Narayanaswamy Srinivasan and Alexandre G {de Brevern}},
doi = {10.1007/s12551-010-0036-1},
year  = {2010},
date = {2010-08-01},
journal = {Biophys Rev},
volume = {2},
number = {3},
pages = {137-147},
abstract = {Protein structures are classically described in terms of secondary structures. Even if the regular secondary structures have relevant physical meaning, their recognition from atomic coordinates has some important limitations such as uncertainties in the assignment of boundaries of helical and β-strand regions. Further, on an average about 50% of all residues are assigned to an irregular state, i.e., the coil. Thus different research teams have focused on abstracting conformation of protein backbone in the localized short stretches. Using different geometric measures, local stretches in protein structures are clustered in a chosen number of states. A prototype representative of the local structures in each cluster is generally defined. These libraries of local structures prototypes are named as "structural alphabets". We have developed a structural alphabet, named Protein Blocks, not only to approximate the protein structure, but also to predict them from sequence. Since its development, we and other teams have explored numerous new research fields using this structural alphabet. We review here some of the most interesting applications.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Reddy:2010aa,
title = {Systematic search for putative new domain families in Mycoplasma gallisepticum genome},
author = {Chilamakuri Cs Reddy and Sane Sudha Rani and Bernard Offmann and R Sowdhamini},
doi = {10.1186/1756-0500-3-98},
year  = {2010},
date = {2010-04-01},
journal = {BMC Res Notes},
volume = {3},
pages = {98},
abstract = {BACKGROUND: Protein domains are the fundamental units of protein structure, function and evolution. The delineation of different domains in proteins is important for classification, understanding of structure, function and evolution. The delineation of protein domains within a polypeptide chain, namely at the genome scale, can be achieved in several ways but may remain problematic in many instances. Difficulties in identifying the domain content of a given sequence arise when the query sequence has no homologues with experimentally determined structure and searching against sequence domain databases also results in insignificant matches. Identification of domains under low sequence identity conditions and lack of structural homologues acquire a crucial importance especially at the genomic scale. FINDINGS: We have developed a new method for the identification of domains in unassigned regions through indirect connections and scaled up its application to the analysis of 434 unassigned regions in 726 protein sequences of Mycoplasma gallisepticum genome. We could establish 71 new domain relationships and probable 63 putative new domain families through intermediate sequences in the unassigned regions, which importantly represent an overall 10% increase in PfamA domain annotation over the direct assignment in this genome. CONCLUSIONS: The systematic analysis of the unassigned regions in the Mycoplasma gallisepticum genome has provided some insight into the possible new domain relationships and putative new domain families. Further investigation of these predicted new domains may prove beneficial in improving the existing domain prediction algorithms.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Groben:2010aa,
title = {Comparative sequence analysis of CP12, a small protein involved in the formation of a Calvin cycle complex in photosynthetic organisms},
author = {René Groben and Dimitrios Kaloudas and Christine A Raines and Bernard Offmann and Stephen C Maberly and Brigitte Gontero},
doi = {10.1007/s11120-010-9542-z},
year  = {2010},
date = {2010-03-01},
journal = {Photosynth Res},
volume = {103},
number = {3},
pages = {183-94},
abstract = {CP12, a small intrinsically unstructured protein, plays an important role in the regulation of the Calvin cycle by forming a complex with phosphoribulokinase (PRK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). An extensive search in databases revealed 129 protein sequences from, higher plants, mosses and liverworts, different groups of eukaryotic algae and cyanobacteria. CP12 was identified throughout the Plantae, apart from in the Prasinophyceae. Within the Chromalveolata, two putative CP12 proteins have been found in the genomes of the diatom Thalassiosira pseudonana and the haptophyte Emiliania huxleyi, but specific searches in further chromalveolate genomes or EST datasets did not reveal any CP12 sequences in other Prymnesiophyceae, Dinophyceae or Pelagophyceae. A species from the Euglenophyceae within the Excavata also appeared to lack CP12. Phylogenetic analysis showed a clear separation into a number of higher taxonomic clades and among different forms of CP12 in higher plants. Cyanobacteria, Chlorophyceae, Rhodophyta and Glaucophyceae, Bryophyta, and the CP12-3 forms in higher plants all form separate clades. The degree of disorder of CP12 was higher in higher plants than in the eukaryotic algae and cyanobacteria apart from the green algal class Mesostigmatophyceae, which is ancestral to the streptophytes. This suggests that CP12 has evolved to become more flexible and possibly take on more general roles. Different features of the CP12 sequences in the different taxonomic groups and their potential functions and interactions in the Calvin cycle are discussed.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Richard2009,
title = {Submersion time, depth, substrate type and sampling method as variation sources of marine periphyton},
author = {M Richard and Camille Trottier and M C J Verdegem and J M E Hussenot},
url = {https://www.sciencedirect.com/science/article/pii/S004484860900619X},
doi = {10.1016/J.AQUACULTURE.2009.07.005},
issn = {0044-8486},
year  = {2009},
date = {2009-10-01},
journal = {Aquaculture},
volume = {295},
number = {3-4},
pages = {209--217},
publisher = {Elsevier},
abstract = {Periphyton is an additional food source in African and Asian brackish and freshwater fish ponds. The present study was a preliminary assessment of periphyton development on artificial substrates in temperate marine ponds. The effects of submersion time, substrate type, water depth, and total or partial sampling methods on the quantity and quality of periphyton collected, were evaluated. Four types of substrate (W: wooden poles, S: smooth fiber-glass strips, m: mosquito screen (1mm-mesh) and M: garden netting (5mm-mesh)) were deployed in a marine pond, and periphyton was collected 15 and 30days later. The total amount of periphyton per substrate unit was collected as one sample or as 5 sub-samples. Results showed that (i) periphyton biomass in a marine pond increased between day 15 and day 30, (ii) more periphyton was collected on mosquito screen than on wooden poles, fiberglass strips and garden netting, (iii) periphyton biomass increased with submersion depth, (iv) sub-sampling leads to an underestimate compared to whole unit sampling, and (v) a correction of periphyton weight must be carried out considering the dissolved inorganic salts present in periphyton samples from marine and brackish ponds. Whole substrate unit sampling using a tube and stopper is recommended to avoid underestimation of periphyton development. Finally, the autotrophic fraction in the periphyton communities was very low compared to periphyton developed on biodegradable substrates in fertilized tropical ponds. Studies on fertilization and use of biodegraded substrates (i.e. long-time submerged wood) are recommended to further optimize periphyton development in temperate marine ponds.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid19705146,
title = {Susceptibility of Phelipanche and Orobanche species to AAL-toxin},
author = {Axel de Zélicourt and Grégory Montiel and Jean-Bernard Pouvreau and Séverine Thoiron and Sabine Delgrange and Philippe Simier and Philippe Delavault},
doi = {10.1007/s00425-009-1008-1},
issn = {1432-2048},
year  = {2009},
date = {2009-10-01},
urldate = {2009-10-01},
journal = {Planta},
volume = {230},
number = {5},
pages = {1047--1055},
abstract = {Fusarium and Alternaria spp. are phytopathogenic fungi which are known to be virulent on broomrapes and to produce sphinganine-analog mycotoxins (SAMs). AAL-toxin is a SAM produced by Alternaria alternata which causes the inhibition of sphinganine N-acyltransferase, a key enzyme in sphingolipid biosynthesis, leading to accumulation of sphingoid bases. These long chain bases (LCBs) are determinant in the occurrence of programmed cell death (PCD) in susceptible plants. We showed that broomrapes are sensitive to AAL-toxin, which is not common plant behavior, and that AAL-toxin triggers cell death at the apex of the radicle as well as LCB accumulation and DNA laddering. We also demonstrated that three Lag1 homologs, encoding components of sphinganine N-acyltransferase in yeast, are present in the Orobanche cumana genome and two of them are mutated leading to an enhanced susceptibility to AAL-toxin. We therefore propose a model for the molecular mechanism governing broomrape susceptibility to the fungus Alternaria alternata.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Tyagi:2009ab,
title = {Analysis of loop boundaries using different local structure assignment methods},
author = {Manoj Tyagi and Aurélie Bornot and Bernard Offmann and Alexandre G {de Brevern}},
doi = {10.1002/pro.198},
year  = {2009},
date = {2009-09-01},
journal = {Protein Sci},
volume = {18},
number = {9},
pages = {1869-81},
abstract = {Loops connect regular secondary structures. In many instances, they are known to play important biological roles. Analysis and prediction of loop conformations depend directly on the definition of repetitive structures. Nonetheless, the secondary structure assignment methods (SSAMs) often lead to divergent assignments. In this study, we analyzed, both structure and sequence point of views, how the divergence between different SSAMs affect boundary definitions of loops connecting regular secondary structures. The analysis of SSAMs underlines that no clear consensus between the different SSAMs can be easily found. Because these latter greatly influence the loop boundary definitions, important variations are indeed observed, that is, capping positions are shifted between different SSAMs. On the other hand, our results show that the sequence information in these capping regions are more stable than expected, and, classical and equivalent sequence patterns were found for most of the SSAMs. This is, to our knowledge, the most exhaustive survey in this field as (i) various databank have been used leading to similar results without implication of protein redundancy and (ii) the first time various SSAMs have been used. This work hence gives new insights into the difficult question of assignment of repetitive structures and addresses the issue of loop boundaries definition. Although SSAMs give very different local structure assignments capping sequence patterns remain efficiently stable.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Tyagi:2009aa,
title = {Protein short loop prediction in terms of a structural alphabet},
author = {Manoj Tyagi and Aurélie Bornot and Bernard Offmann and Alexandre G {de Brevern}},
doi = {10.1016/j.compbiolchem.2009.06.002},
year  = {2009},
date = {2009-08-01},
journal = {Comput Biol Chem},
volume = {33},
number = {4},
pages = {329-33},
abstract = {Loops connect regular secondary structures. In many instances, they are known to play crucial biological roles. To bypass the limitation of secondary structure description, we previously defined a structural alphabet composed of 16 structural prototypes, called Protein Blocks (PBs). It leads to an accurate description of every region of 3D protein backbones and has been used in local structure prediction. In the present study, we used our structural alphabet to predict the loops connecting two repetitive structures. Thus, we showed interest to take into account the flanking regions, leading to prediction rate improvement up to 19.8%, but we also underline the sensitivity of such an approach. This research can be used to propose different structures for the loops and to probe and sample their flexibility. It is a useful tool for ab initio loop prediction and leads to insights into flexible docking approach.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{sandhya2009length,
title = {Length variations amongst protein domain superfamilies and consequences on structure and function},
author = {Sankaran Sandhya and Saane Sudha Rani and Barah Pankaj and Madabosse Kande Govind and Bernard Offmann and Narayanaswamy Srinivasan and Ramanathan Sowdhamini},
url = {https://doi.org/10.1371/journal.pone.0004981},
doi = {10.1371/journal.pone.0004981},
year  = {2009},
date = {2009-01-01},
journal = {PLoS One},
volume = {4},
number = {3},
pages = {e4981},
publisher = {Public Library of Science},
abstract = {Background: Related protein domains of a superfamily can be specified by proteins of diverse lengths. The structural and functional implications of indels in a domain scaffold have been examined. Methodology: In this study, domain superfamilies with large length variations (more than 30% difference from average domain size, referred as 'length-deviant' superfamilies and 'length-rigid' domain superfamilies (&lt;10% length difference from average domain size) were analyzed for the functional impact of such structural differences. Our delineated dataset, derived from an objective algorithm, enables us to address indel roles in the presence of peculiar structural repeats, functional variation, protein-protein interactions and to examine 'domain contexts' of proteins tolerant to large length variations. Amongst the top-10 length-deviant superfamilies analyzed, we found that 80% of length-deviant superfamilies possess distant internal structural repeats and nearly half of them acquired diverse biological functions. In general, length-deviant superfamilies have higher chance, than length-rigid superfamilies, to be engaged in internal structural repeats. We also found that approximately 40% of length-deviant domains exist as multi-domain proteins involving interactions with domains from the same or other superfamilies. Indels, in diverse domain superfamilies, were found to participate in the accretion of structural and functional features amongst related domains. With specific examples, we discuss how indels are involved directly or indirectly in the generation of oligomerization interfaces, introduction of substrate specificity, regulation of protein function and stability. Conclusions: Our data suggests a multitude of roles for indels that are specialized for domain members of different domain superfamilies. These specialist roles that we observe and trends in the extent of length variation could influence decision making in modeling of new superfamily members. Likewise, the observed limits of length variation, specific for each domain superfamily would be particularly relevant in the choice of alignment length search filters commonly applied in protein sequence analysis.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Thangudu:2008aa,
title = {Analysis on conservation of disulphide bonds and their structural features in homologous protein domain families},
author = {Ratna R Thangudu and Malini Manoharan and N Srinivasan and Frédéric Cadet and R Sowdhamini and Bernard Offmann},
doi = {10.1186/1472-6807-8-55},
year  = {2008},
date = {2008-12-01},
journal = {BMC Struct Biol},
volume = {8},
pages = {55},
abstract = {BACKGROUND: Disulphide bridges are well known to play key roles in stability, folding and functions of proteins. Introduction or deletion of disulphides by site-directed mutagenesis have produced varying effects on stability and folding depending upon the protein and location of disulphide in the 3-D structure. Given the lack of complete understanding it is worthwhile to learn from an analysis of extent of conservation of disulphides in homologous proteins. We have also addressed the question of what structural interactions replaces a disulphide in a homologue in another homologue. 
RESULTS: Using a dataset involving 34,752 pairwise comparisons of homologous protein domains corresponding to 300 protein domain families of known 3-D structures, we provide a comprehensive analysis of extent of conservation of disulphide bridges and their structural features. We report that only 54% of all the disulphide bonds compared between the homologous pairs are conserved, even if, a small fraction of the non-conserved disulphides do include cytoplasmic proteins. Also, only about one fourth of the distinct disulphides are conserved in all the members in protein families. We note that while conservation of disulphide is common in many families, disulphide bond mutations are quite prevalent. Interestingly, we note that there is no clear relationship between sequence identity between two homologous proteins and disulphide bond conservation. Our analysis on structural features at the sites where cysteines forming disulphide in one homologue are replaced by non-Cys residues show that the elimination of a disulphide in a homologue need not always result in stabilizing interactions between equivalent residues. 
CONCLUSION: We observe that in the homologous proteins, disulphide bonds are conserved only to a modest extent. Very interestingly, we note that extent of conservation of disulphide in homologous proteins is unrelated to the overall sequence identity between homologues. The non-conserved disulphides are often associated with variable structural features that were recruited to be associated with differentiation or specialisation of protein function.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{pmid18636683,
title = {Antioxidant and free radical scavenging properties of marennine, a blue-green polyphenolic pigment from the diatom Haslea ostrearia (Gaillon/Bory) Simonsen responsible for the natural greening of cultured oysters},
author = {Jean-Bernard Pouvreau and Michèle Morançais and Frédéric Taran and Philippe Rosa and Laurent Dufossé and Fabienne Guérard and Serge Pin and Joël Fleurence and Pierre Pondaven},
doi = {10.1021/jf073187n},
issn = {1520-5118},
year  = {2008},
date = {2008-08-01},
urldate = {2008-08-01},
journal = {J Agric Food Chem},
volume = {56},
number = {15},
pages = {6278--6286},
abstract = {Among microalgae, the marine diatom Haslea ostrearia has the distinctive feature of synthesizing and releasing, into the surrounding environment, a blue-green polyphenolic pigment called marennine. The oyster-breeding industry commonly makes use of this natural phenomenon for the greening of oysters grown in the ponds of the French Atlantic coast. This article reports the in vitro antioxidant properties of pure marennine. Two kinds of evaluation systems were adopted to test the antioxidative activity of marennine: antioxidant capacity assays (beta-carotene and thymidine protection assays and iron reducing power assay) and free radical scavenging assays (DPPH*, O2*-, and HO*). In almost all cases, marennine exhibited significantly higher antioxidative and free radical scavenging activities than natural and synthetic antioxidants commonly used in food, as shown by comparing median effective concentration (EC 50) values, for each test independently. This medium molecular weight polyphenol (around 10 kDa) from microalgae is thus a potentially useful natural antioxidant. Because of its blue-coloring property and water solubility, it could also be used as a natural food-coloring additive.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Reddy:2008aa,
title = {PURE: a webserver for the prediction of domains in unassigned regions in proteins},
author = {Chilamakuri C S Reddy and Khader Shameer and Bernard Offmann and Ramanathan Sowdhamini},
doi = {10.1186/1471-2105-9-281},
year  = {2008},
date = {2008-06-01},
journal = {BMC Bioinformatics},
volume = {9},
pages = {281},
abstract = {BACKGROUND: Protein domains are the structural and functional units of proteins. The ability to parse proteins into different domains is important for effective classification, understanding of protein structure, function, and evolution and is hence biologically relevant. Several computational methods are available to identify domains in the sequence. Domain finding algorithms often employ stringent thresholds to recognize sequence domains. Identification of additional domains can be tedious involving intense computation and manual intervention but can lead to better understanding of overall biological function. In this context, the problem of identifying new domains in the unassigned regions of a protein sequence assumes a crucial importance. RESULTS: We had earlier demonstrated that accumulation of domain information of sequence homologues can substantially aid prediction of new domains. In this paper, we propose a computationally intensive, multi-step bioinformatics protocol as a web server named as PURE (Prediction of Unassigned REgions in proteins) for the detailed examination of stretches of unassigned regions in proteins. Query sequence is processed using different automated filtering steps based on length, presence of coiled-coil regions, transmembrane regions, homologous sequences and percentage of secondary structure content. Later, the filtered sequence segments and their sequence homologues are fed to PSI-BLAST, cd-hit and Hmmpfam. Data from the various programs are integrated and information regarding the probable domains predicted from the sequence is reported. CONCLUSION: We have implemented PURE protocol as a web server for rapid and comprehensive analysis of unassigned regions in the proteins. This server integrates data from different programs and provides information about the domains encoded in the unassigned regions.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Tyagi:2008aa,
title = {Protein structure mining using a structural alphabet},
author = {M Tyagi and A G {de Brevern} and N Srinivasan and Bernard Offmann},
doi = {10.1002/prot.21776},
year  = {2008},
date = {2008-05-01},
journal = {Proteins},
volume = {71},
number = {2},
pages = {920-37},
abstract = {We present a comprehensive evaluation of a new structure mining method called PB-ALIGN. It is based on the encoding of protein structure as 1D sequence of a combination of 16 short structural motifs or protein blocks (PBs). PBs are short motifs capable of representing most of the local structural features of a protein backbone. Using derived PB substitution matrix and simple dynamic programming algorithm, PB sequences are aligned the same way amino acid sequences to yield structure alignment. PBs are short motifs capable of representing most of the local structural features of a protein backbone. Alignment of these local features as sequence of symbols enables fast detection of structural similarities between two proteins. Ability of the method to characterize and align regions beyond regular secondary structures, for example, N and C caps of helix and loops connecting regular structures, puts it a step ahead of existing methods, which strongly rely on secondary structure elements. PB-ALIGN achieved efficiency of 85% in extracting true fold from a large database of 7259 SCOP domains and was successful in 82% cases to identify true super-family members. On comparison to 13 existing structure comparison/mining methods, PB-ALIGN emerged as the best on general ability test dataset and was at par with methods like YAKUSA and CE on nontrivial test dataset. Furthermore, the proposed method performed well when compared to flexible structure alignment method like FATCAT and outperforms in processing speed (less than 45 s per database scan). This work also establishes a reliable cut-off value for the demarcation of similar folds. It finally shows that global alignment scores of unrelated structures using PBs follow an extreme value distribution. PB-ALIGN is freely available on web server called Protein Block Expert (PBE) at http://bioinformatics.univ-reunion.fr/PBE/.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Sandhya:2008aa,
title = {CUSP: an algorithm to distinguish structurally conserved and unconserved regions in protein domain alignments and its application in the study of large length variations},
author = {Sankaran Sandhya and Barah Pankaj and Madabosse Kande Govind and Bernard Offmann and Narayanaswamy Srinivasan and Ramanathan Sowdhamini},
doi = {10.1186/1472-6807-8-28},
year  = {2008},
date = {2008-05-01},
journal = {BMC Struct Biol},
volume = {8},
pages = {28},
abstract = {BACKGROUND: Distantly related proteins adopt and retain similar structural scaffolds despite length variations that could be as much as two-fold in some protein superfamilies. In this paper, we describe an analysis of indel regions that accommodate length variations amongst related proteins. We have developed an algorithm CUSP, to examine multi-membered PASS2 superfamily alignments to identify indel regions in an automated manner. Further, we have used the method to characterize the length, structural type and biochemical features of indels in related protein domains. RESULTS: CUSP, examines protein domain structural alignments to distinguish regions of conserved structure common to related proteins from structurally unconserved regions that vary in length and type of structure. On a non-redundant dataset of 353 domain superfamily alignments from PASS2, we find that 'length- deviant' protein superfamilies show &gt; 30% length variation from their average domain length. 60% of additional lengths that occur in indels are short-length structures (&lt; 5 residues) while 6% of indels are &gt; 15 residues in length. Structural types in indels also show class-specific trends. CONCLUSION: The extent of length variation varies across different superfamilies and indels show class-specific trends for preferred lengths and structural types. Such indels of different lengths even within a single protein domain superfamily could have structural and functional consequences that drive their selection, underlying their importance in similarity detection and computational modelling. The availability of systematic algorithms, like CUSP, should enable decision making in a domain superfamily-specific manner.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{chilamakuri2007pure,
title = {PURE: a web server for querying the relationship between pre-existing domains and unassigned regions in proteins},
author = {Sekhar Reddy C Chilamakuri and Shameer Khader and Bernard Offmann and Ramanathan Sowdhamini},
doi = {doi:10.1038/nprot.2007.486},
year  = {2007},
date = {2007-11-01},
journal = {Nature Protocols},
publisher = {Nature Publishing Group},
abstract = {Protein domains are the structural and functional units of proteins. The ability to parse proteins into different domains is important for effective classification, understanding of protein structure, function and evolution and is hence biologically relevant. Several computational methods are available to identify domains in the sequence. Domain finding algorithms often employ stringent thresholds to recognize sequence domains. Identification of additional domains can be tedious involving intense computation and manual intervention but can lead to better understanding of overall biological function. In this context, the problem of identifying new domains in the unassigned regions of a protein sequence assumes a crucial importance. We report the availability of a convenient server for the domain prediction in unassigned regions in proteins (PURE) which can be accessed at http://caps.ncbs.res.in/PURE/ year = 2007},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Thangudu:2007aa,
title = {Analycys: a database for conservation and conformation of disulphide bonds in homologous protein domains},
author = {Ratna R Thangudu and Priyanka Sharma and N Srinivasan and Bernard Offmann},
doi = {10.1002/prot.21318},
year  = {2007},
date = {2007-05-01},
journal = {Proteins},
volume = {67},
number = {2},
pages = {255-61},
abstract = {Disulphide bonds in proteins are known to play diverse roles ranging from folding to structure to function. Thorough knowledge of the conservation status and structural state of the disulphide bonds will help in understanding of the differences in homologous proteins. Here we present a database for the analysis of conservation and conformation of disulphide bonds in SCOP structural families. This database has a wide range of applications including mapping of disulphide bond mutation patterns, identification of disulphide bonds important for folding and stabilization, modeling of protein tertiary structures and in protein engineering. The database can be accessed at: http://bioinformatics.univ-reunion.fr/analycys/.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{BernardOffmann2007,
title = {Local Protein Structures},
author = {Bernard Offmann and Manoj Tyagi and Alexandre G. {de Brevern}},
url = {http://www.eurekaselect.com/node/78709/article},
doi = {10.2174/157489307781662105},
issn = {1574-8936/2212-392X},
year  = {2007},
date = {2007-01-01},
journal = {Current Bioinformatics},
volume = {2},
number = {3},
pages = {165-202},
abstract = {Protein structures are classically described as composed of two regular states, the α-helices and the β-strands and one non-regular and variable state, the coil. Nonetheless, this simple definition of secondary structures hides numerous limitations. In fact, the rules for secondary structure assignment are complex. Thus, numerous assignment methods based on different criteria have emerged leading to heterogeneous and diverging results. In the same way, 3 states may over-simplify the description of protein structure; 50&#x25; of all residues, i.e., the coil, are not genuinely described even when it encompass precise local protein structures. Description of local protein structures have hence focused on the elaboration of complete sets of small prototypes or structural alphabets, able to analyze local protein structures and to approximate every part of the protein backbone. They have also been used to predict the protein backbone conformation and in ab initio/ de novo methods. In this paper, we review different approaches towards the description of local structures, mainly through their description in terms of secondary structures and in terms of structural alphabets. We provide some insights into their potential applications.},
keywords = {ab initio, out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{bornot2007flexible,
title = {How flexible protein structures are? New questions on the protein structure plasticity.},
author = {Aurélie Bornot and Bernard Offmann and Alexandre {de Brevern}},
year  = {2007},
date = {2007-01-01},
journal = {Bioforum Europe},
number = {11},
pages = {24},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@book{swapna2007evolutionary,
title = {Evolutionary dynamics of protein-protein interactions. A case study using the DJ-1/PfpI family of enzyme.},
author = {LS Swapna and Bernard Offmann and N Srinivasan},
year  = {2007},
date = {2007-01-01},
journal = {Knowledge Discovery in Bioinformatics: Techniques, Methods, and Applications},
pages = {209--231},
publisher = {John Wiley & Sons, Inc.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {book}
}
@article{Gardebien:2006aa,
title = {Construction of a 3D model of CP12, a protein linker},
author = {Fabrice Gardebien and Rajesh R Thangudu and Brigitte Gontero and Bernard Offmann},
doi = {10.1016/j.jmgm.2005.12.003},
year  = {2006},
date = {2006-10-01},
journal = {J Mol Graph Model},
volume = {25},
number = {2},
pages = {186-95},
abstract = {The chloroplast protein CP12 is known to play a leading role in a complex formation with the enzymes GAPDH and PRK. As a preliminary step towards the understanding of the complex formation mechanism and the exact role of this protein linker, a comparative modelling of the CP12 protein of the green alga Chlamydomonas reinhardtii was performed. Because of the very few structural information and poor template similarities, the derivation of the model consisted in an iterative trial-and-error procedure using the comparative modelling program MODELLER, the following three structure validation programs PROCHECK, PROSA, and WHATIF, and molecular mechanics energy refinement of the model using the program CHARMM. The analysis of the final model reveals a scaffold of key residues that is believed to be essential in the folding mechanism and that coincides with the residues conserved throughout the CP12 family. Our results suggest that this protein is a typical disordered protein. Finally, the various mechanisms by which the CP12 protein can self-interact or binds to other enzymes are discussed in light of its modelled structure and characteristics.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Tyagi:2006aa,
title = {A substitution matrix for structural alphabet based on structural alignment of homologous proteins and its applications},
author = {Manoj Tyagi and Venkataraman S Gowri and Narayanaswamy Srinivasan and Alexandre G {de Brevern} and Bernard Offmann},
doi = {10.1002/prot.21087},
year  = {2006},
date = {2006-10-01},
journal = {Proteins},
volume = {65},
number = {1},
pages = {32-9},
abstract = {Analysis of protein structures based on backbone structural patterns known as structural alphabets have been shown to be very useful. Among them, a set of 16 pentapeptide structural motifs known as protein blocks (PBs) has been identified and upon which backbone model of most protein structures can be built. PBs allows simplification of 3D space onto 1D space in the form of sequence of PBs. Here, for the first time, substitution probabilities of PBs in a large number of aligned homologous protein structures have been studied and are expressed as a simplified 16 x 16 substitution matrix. The matrix was validated by benchmarking how well it can align sequences of PBs rather like amino acid alignment to identify structurally equivalent regions in closely or distantly related proteins using dynamic programming approach. The alignment results obtained are very comparable to well established structure comparison methods like DALI and STAMP. Other interesting applications of the matrix have been investigated. We first show that, in variable regions between two superimposed homologous proteins, one can distinguish between local conformational differences and rigid-body displacement of a conserved motif by comparing the PBs and their substitution scores. Second, we demonstrate, with the example of aspartic proteinases, that PBs can be efficiently used to detect the lobe/domain flexibility in the multidomain proteins. Lastly, using protein kinase as an example, we identify regions of conformational variations and rigid body movements in the enzyme as it is changed to the active state from an inactive state.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Tyagi:2006ab,
title = {Protein Block Expert (PBE): a web-based protein structure analysis server using a structural alphabet},
author = {M Tyagi and P Sharma and C S Swamy and F Cadet and N Srinivasan and A G {de Brevern} and Bernard Offmann},
doi = {10.1093/nar/gkl199},
year  = {2006},
date = {2006-07-01},
journal = {Nucleic Acids Res},
volume = {34},
number = {Web Server issue},
pages = {W119-23},
abstract = {Encoding protein 3D structures into 1D string using short structural prototypes or structural alphabets opens a new front for structure comparison and analysis. Using the well-documented 16 motifs of Protein Blocks (PBs) as structural alphabet, we have developed a methodology to compare protein structures that are encoded as sequences of PBs by aligning them using dynamic programming which uses a substitution matrix for PBs. This methodology is implemented in the applications available in Protein Block Expert (PBE) server. PBE addresses common issues in the field of protein structure analysis such as comparison of proteins structures and identification of protein structures in structural databanks that resemble a given structure. PBE-T provides facility to transform any PDB file into sequences of PBs. PBE-ALIGNc performs comparison of two protein structures based on the alignment of their corresponding PB sequences. PBE-ALIGNm is a facility for mining SCOP database for similar structures based on the alignment of PBs. Besides, PBE provides an interface to a database (PBE-SAdb) of preprocessed PB sequences from SCOP culled at 95% and of all-against-all pairwise PB alignments at family and superfamily levels. PBE server is freely available at http://bioinformatics.univ-reunion.fr/PBE/.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Thangudu:2005aa,
title = {Native and modeled disulfide bonds in proteins: knowledge-based approaches toward structure prediction of disulfide-rich polypeptides},
author = {Ratna Rajesh Thangudu and A Vinayagam and G Pugalenthi and A Manonmani and Bernard Offmann and R Sowdhamini},
doi = {10.1002/prot.20369},
year  = {2005},
date = {2005-03-01},
journal = {Proteins},
volume = {58},
number = {4},
pages = {866-79},
abstract = {Structure prediction and three-dimensional modeling of disulfide-rich systems are challenging due to the limited number of such folds in the structural databank. We exploit the stereochemical compatibility of substructures in known protein structures to accommodate disulfide bonds in predicting the structures of disulfide-rich polypeptides directly from disulfide connectivity pattern and amino acid sequence in the absence of structural homologs and any other structural information. This knowledge-based approach is illustrated using structure prediction of 40 nonredundant bioactive disulfide-rich polypeptides such as toxins, growth factors, and endothelins available in the structural databank. The polypeptide conformation could be predicted in 35 out of 40 nonredundant entries (87%). Nonhomologous templates could be identified and models could be obtained within 2 A deviation from the query in 29 peptides (72%). This procedure can be accessed from the World Wide Web (http://www.ncbs.res.in/ approximately faculty/mini/dsdbase/dsdbase.html).},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Besnard:2003aa,
title = {Characterisation of the phosphoenolpyruvate carboxylase gene family in sugarcane (Saccharum spp.)},
author = {G Besnard and G Pinçon and A D'Hont and J-Y Hoarau and Frédéric Cadet and Bernard Offmann},
doi = {10.1007/s00122-003-1268-2},
year  = {2003},
date = {2003-08-01},
journal = {Theoretical and Applied Genetics},
volume = {107},
number = {3},
pages = {470-8},
abstract = {Phosphoenolpyruvate carboxylases (PEPCs) are encoded by a small multigenic family. In order to characterise this gene family in sugarcane, seven DNA fragments displaying a high homology with grass PEPC genes were isolated using polymerase chain reaction-based cloning. A phylogenetic study revealed the existence of four main PEPC gene lineages in grasses and particularly in sugarcane. Moreover, this analysis suggests that grass C4 PEPC has likely derived from a root pre-existing isoform in an ancestral species. Using the Northern-dot-blot method, we studied the expression of the four PEPC gene classes in sugarcane cv. R570. We confirmed that transcript accumulation of the C4 PEPC gene (ppc-C4) mainly occurs in the green leaves and is light-induced. We also showed that another member of this gene family (ppc-aR) is more highly transcribed in the roots. The constitutive expression for a previously characterised gene (ppc-aL2) was confirmed. Lastly, the transcript accumulation of the fourth PEPC gene class (ppc-aL1) was not revealed. Length polymorphism in non-coding regions for three PEPC gene lineages enabled us to develop sequence-tagged site PEPC markers in sugarcane. We analysed the segregation of PEPC fragments in self-pollinated progenies of cv. R570 and found co-segregating fragments for two PEPC gene lineages. This supports the hypothesis that diversification of the PEPC genes involved duplications, probably in tandem.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@inproceedings{offmann2003segregation,
title = {Segregation of resistance to Xanthomonas albilineans in a sugarcane progeny},
author = {Bernard Offmann and Louis Marie Raboin and Julien Notaise},
year  = {2003},
date = {2003-01-01},
journal = {The Journal of Nature},
volume = {15},
number = {1},
pages = {113--124},
publisher = {Bourbon sciences},
keywords = {out_lab},
pubstate = {published},
tppubtype = {inproceedings}
}
@article{Hoarau:2002aa,
title = {Genetic dissection of a modern sugarcane cultivar ( Saccharum spp.).II. Detection of QTLs for yield components},
author = {J-Y Hoarau and L Grivet and Bernard Offmann and L-M Raboin and J-P Diorflar and J Payet and M Hellmann and A D'Hont and J-C Glaszmann},
doi = {10.1007/s00122-002-1047-5},
year  = {2002},
date = {2002-11-01},
journal = {Theoretical and Applied Genetics},
volume = {105},
number = {6-7},
pages = {1027-1037},
abstract = {The genetics of current sugarcane cultivars ( Saccharum spp.) is outstandingly complex, due to a high ploidy level and an interspecific origin which leads to the presence of numerous chromosomes belonging to two ancestral genomes. In order to analyse the inheritance of quantitative traits, we have undertaken an extensive Quantitative Trait Allele (QTA) mapping study based on a population of 295 progenies derived from the selfing of cultivar R570, using about 1,000 AFLP markers scattered on about half of the genome. The population was evaluated in a replicated trial for four basic yield components, plant height, stalk number, stalk diameter and brix, in two successive crop-cycles. Forty putative QTAs were found for the four traits at P = 5 x 10(-3), of which five appeared in both years. Their individual size ranged between 3 and 7% of the whole variation. The stability across years was improved when limiting threshold stringency. All these results depict the presence in the genome of numerous QTAs, with little effects, fluctuating slightly across cycles, on the verge to being perceptible given the experimental resolution. Epistatic interactions were also explored and 41 independent di-genic interactions were found at P = (5 x 10(-3))(2). Altogether the putative genetic factors revealed here explain from 30 to 55% of the total phenotypic variance depending on the trait. The tentative assignment of some QTAs to the ancestral genomes showed a small majority of contributions as expected from the ancestral phenotypes. This is the first extensive QTL mapping study performed in cultivated sugarcane.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{Besnard:2002aa,
title = {Assessment of the C(4) phosphoenolpyruvate carboxylase gene diversity in grasses (Poaceae)},
author = {Guillaume Besnard and Bernard Offmann and Christine Robert and Claude Rouch and Frédéric Cadet},
doi = {10.1007/s00122-001-0851-7},
year  = {2002},
date = {2002-08-01},
journal = {Theoretical and Applied Genetics},
volume = {105},
number = {2-3},
pages = {404-412},
abstract = {C(4) phosphoenolpyruvate carboxylase (PEPC) is a key enzyme in the C(4) photosynthetic pathway. To analyze the diversity of the corresponding gene in grasses, we designed PCR primers to specifically amplify C(4) PEPC cDNA fragments. Using RT-PCR, we generated partial PEPC cDNA sequences in several grasses displaying a C(4) photosynthetic pathway. All these sequences displayed a high homology (78-99%) with known grass C(4) PEPCs. PCR amplification did not occur in two grasses that display the C(3) photosynthetic pathway, and therefore we assumed that all generated sequences corresponded to C(4) PEPC transcripts. Based on one large cDNA segment, phylogenetic reconstruction enabled us to assess the relationships between 22 grass species belonging to the subfamilies Panicoideae, Arundinoideae and Chloridoideae. The phylogenetic relationships between species deduced from C(4) PEPC sequences were similar to those deduced from other molecular data. The sequence evolution of the C(4) PEPC isoform was faster than in the other PEPC isoforms. Finally, the utility of the C(4) PEPC gene phylogeny to study the evolution of C(4) photosynthesis in grasses is discussed.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1081/SL-120013888,
title = {Enzymes as structural tool in infrared spectroscopy},
author = {Bernard Offmann and Frédéric Cadet},
url = {https://www.tandfonline.com/doi/abs/10.1081/SL-120013888},
doi = {10.1081/SL-120013888},
year  = {2002},
date = {2002-01-01},
journal = {Spectroscopy Letters},
volume = {35},
number = {4},
pages = {523-526},
publisher = {Taylor & Francis},
abstract = {The complexity of IR spectra of some compounds, particularly biological molecules, is a major obstacle in assigning or characterizing their IR bands. In this short communication, the potential use of enzymes for infrared bands characterization and assignments is demonstrated and discussed.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{https://doi.org/10.1002/bmb.2002.494030040069,
title = {Redox-active disulfides in a plant light switch: A Pbl problem*},
author = {Bernard Offmann and Frédéric Cadet},
url = {https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1002/bmb.2002.494030040069},
doi = {https://doi.org/10.1002/bmb.2002.494030040069},
year  = {2002},
date = {2002-01-01},
journal = {Biochemistry and Molecular Biology Education},
volume = {30},
number = {4},
pages = {249-254},
abstract = {A problem for students on the mode of activation of light-regulated NADP-dependent malate dehydrogenase is presented here as a series of questions requiring the interpretation of experimental data.},
keywords = {C4 photosynthesis, disulfides, light activation, NADP malate dehydrogenase, out_lab, problem based learning, redox},
pubstate = {published},
tppubtype = {article}
}
@article{hoarau2001genetic,
title = {Genetic dissection of a modern sugarcane cultivar (Saccharum spp.). I. Genome mapping with AFLP markers},
author = {J-Y Hoarau and Bernard Offmann and Angélique D'Hont and A-M Risterucci and D Roques and J-C Glaszmann and Laurent Grivet},
year  = {2001},
date = {2001-01-01},
journal = {Theoretical and Applied Genetics},
volume = {103},
number = {1},
pages = {84--97},
publisher = {Springer-Verlag},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@inproceedings{raboin2001undertaking,
title = {Undertaking genetic mapping of sugarcane smut resistance},
author = {Louis-Marie Raboin and Bernard Offmann and Jean-Yves Hoarau and Julien Notaise and Laurent Costet and Hugues Telismart and Danièle Roques and Philippe Rott and Jean-Christophe Glaszmann and Angélique D'Hont},
year  = {2001},
date = {2001-01-01},
booktitle = {Proc S Afr Sug Technol Ass},
volume = {75},
pages = {94--98},
abstract = {Smut is one of the most important diseases of sugarcane and has a worldwide distribution. It can cause severe yield losses when a susceptible variety is grown in a smut infested area. Resistance is therefore a major concern for most sugarcane breeding centers. A study on the genetic determinism underlying sugarcane smut resistance was initiated. A genetic mapping strategy was cho- sen that focused on a cross between cultivar R 570 (resistant) and cultivar MQ 76/53 (highly susceptible) which showed a segregation for smut resistance in a preliminary field trial. An AFLP map is being constructed for both parents of the cross. At the same time, field trials and greenhouse experiments have begun using different artificial inoculation methods to assess the resistance of 200 individual progeny.This paper presents first results on smut occurrence among this progeny and correlations between segregating markers and re- sistance to smut. Other characters have also been observed (Brix, number of stalks, rust resistance). The possibility of iden- tifying the different components involved in smut resistance and the interest of locus specific markers (SSR, resistance gene analogs, etc) to refine the genetic map are discussed.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {inproceedings}
}
@article{besnard2001phosphoenolpyruvate,
title = {Phosphoenolpyruvate carboxylase cDNA phylogeny to investigate the C4 photosynthetic pathway evolution in grasses},
author = {Guillaume Besnard and Bernard Offmann and Christine Robert and Pascal Baret and Claude Rouch and Frédéric Cadet},
year  = {2001},
date = {2001-01-01},
journal = {Science Access},
volume = {3},
number = {1},
publisher = {CSIRO},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@phdthesis{offmann2000caracterisation,
title = {Caractérisation et analyse génétique de la résistance de la canne à sucre à Xanthomonas albilineans},
author = {Bernard Offmann},
year  = {2000},
date = {2000-01-01},
school = {La Réunion},
keywords = {out_lab},
pubstate = {published},
tppubtype = {phdthesis}
}
@mastersthesis{offmann1997cartographie,
title = {Cartographie génétique et recherche de QTLs chez un cultivar élite de canne à sucre (Saccharum spp) au moyen de marqueurs AFLP},
author = {Bernard Offmann},
year  = {1997},
date = {1997-07-01},
school = {Université de Paris VII},
keywords = {out_lab},
pubstate = {published},
tppubtype = {mastersthesis}
}
@article{Cadet:97,
title = {Simultaneous Determination of Sugars by Multivariate Analysis Applied to Mid-Infrared Spectra of Biological Samples},
author = {Frédéric Cadet and Christine Robert and Bernard Offmann},
url = {https://doi.org/10.1366/0003702971940224},
doi = {10.1366/0003702971940224},
year  = {1997},
date = {1997-03-01},
urldate = {1997-03-01},
journal = {Appl. Spectrosc.},
volume = {51},
number = {3},
pages = {369--375},
publisher = {OSA},
abstract = {We have investigated the use of principal component analysis (PCA) to describe and assess mid-infrared spectral data obtained from complex biological samples containing sucrose, fructose, and glucose. The correlation coefficients between spectral data and chemical values of each variable (sucrose, glucose, fructose, total sugars, and reducing sugars) showed that in each case, axes 1, 3, 4, and 5 had the highest values. These values also indicated which axes each variable was mostly correlated with. The results also showed that the samples were distributed according to their sucrose concentrations (or total sugars) along a concentration gradient in the projection plan formed between axes 1 and 3. No clear discrimination according to concentration was observed with other factorial maps. Prediction equations that linked sucrose, fructose, glucose, total sugar, and reducing sugars concentrations to the spectral data were established by regression on the principal component. Very high correlation coefficients values between the first 10 axes and the chemical values were obtained (between 0.9757 and 0.998). From such aqueous biological samples containing a ternary mixture of sucrose, fructose, and glucose, it was possible to (1) identify the characteristic IR bands of these different sugars (and their combination: reducing sugars/total sugars) and (2) to specifically measure their concentrations with a relatively good accuracy.},
keywords = {Applied spectroscopy, Fourier transform infrared spectroscopy, Fourier transforms, Infrared radiation, out_lab, Spectrophotometry, Spectroscopy},
pubstate = {published},
tppubtype = {article}
}
@article{doi:10.1021/jf960700g,
title = {Direct Spectroscopic Sucrose Determination of Raw Sugar Cane Juices},
author = {Frédéric Cadet and Bernard Offmann},
url = {https://doi.org/10.1021/jf960700g},
doi = {10.1021/jf960700g},
year  = {1997},
date = {1997-01-01},
journal = {Journal of Agricultural and Food Chemistry},
volume = {45},
number = {1},
pages = {166-171},
abstract = {A more accurate, less time-consuming, and nonpolluting spectroscopic method than the currently used HPLC or polarimetric methods is proposed for the routine quantitative determination of sucrose in complex biological samples. Opaque raw sugar cane juices representative of a sugar cane harvest are analyzed by Fourier transformed mid-infrared attenuated total reflectance, and the spectral data are processed by principal component analysis (PCA) and principal component regression (PCR). The most suitable region for the measurement of sucrose was found to be the 1250−800 cm-1 region. The spectroscopic representation of the first axis as assessed by PCA in this spectral region featured characteristic absorption bands of sucrose. By PCR on the spectral data from a calibration set, a prediction equation was established to predict sucrose content in unknown samples. Good overall predictions were obtained. The values of the predicted sucrose concentration were more accurate (bias = 0.041 g/100 mL) than those obtained by direct polarimetry (bias = −0.163 g/100 mL). The method is validated on a panel of 1267 samples representative of a sugar cane harvest.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{cadet1996extraction,
title = {Extraction of Characteristic Bands of Sugars by Multidimensional Analysis of Their Infrared Spectra.},
author = {Frédéric Cadet and Bernard Offmann},
url = {https://doi.org/10.1080/00387019608006668},
doi = {10.1080/00387019608006668},
year  = {1996},
date = {1996-01-01},
journal = {Spectroscopy letters},
volume = {29},
number = {3},
pages = {523--536},
publisher = {Taylor & Francis},
abstract = {Collected Mid-IR Attenuated Total Reflectance (ATR) spectra of various sugars were assessed by multidimensional statistical analysis. Through Principal Component Analysis (PCA) of collected spectra of various pure 10% sugar solutions and from the spectroscopic representation of the factorial axes, characteristic frequencies of monosaccharides and oligosaccharides were directly and automatically obtained within a few seconds. Monosugars are characterised by a hollow at 998 cm−1 and by a single unique major peak (1049 cm−1) in the 1075–1030 cm−1 region while oligosaccharides showed three characteristic bands in the same region, the major peak is shifted to 1033 cm−1. Owing to the glycosidic link vibrational motion, oligosaccharides are also characterised by a band at 998 cm−1. Spectroscopic representation of the axes issued of data from both sugar families (mixture of mono and oligosaccharides) is an average of the two individual spectral patterns. Predictive measures of concentrations of sugar solutions were performed by principal component regression (PCR) of the factorial coordinates and prediction equations were obtained. The predicted concentrations of standard 10% pure sugar solutions averaged 10. 069% and 9. 909% for monosugars and oligosugars respectively and a concentration of 10. 015% from the mixed set of data was obtained. The ability of these factorial coordinates to predict quantitative variable are good with correlation coefficients ranging from 97. 4% to 99. 9%.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{cadet1996evidence,
title = {Evidence for Potassium-Sucrose Interaction in Biological Mid-Infrared Spectra by Multidimensional Analysis},
author = {Frédéric Cadet and Bernard Offmann},
url = {https://doi.org/10.1080/00387019608007128},
doi = {10.1080/00387019608007128},
year  = {1996},
date = {1996-01-01},
journal = {Spectroscopy letters},
volume = {29},
number = {7},
pages = {1353--1365},
publisher = {Taylor & Francis},
abstract = {Complex-formation between carbohydrates and cations could have important biological implications. In this work, Mid-Infrared spectra of pure sucrose solutions and of biological solutions containing sucrose and potassium ions (K+) were investigated by Principal Component Analysis (PGA). By direct examination of the Mid-Infrared spectra of the biological solutions containing K+ ions, no interactions between the cations and sucrose molecules could be observed. However, when the spectral pattern obtained by PCA and which is associated with sucrose, was examined, splitting and shifts in the characteristic absorption bands were observed owing to interactions between sucrose molecules and K+ ions. The 997 cm-1 peak which had a visible shoulder at 991 cm-1 and that is observed in pure solutions, was decomposed in the biological solutions into 3 distinct peaks at 1004, 996 and 990 cm-1. The two peaks centered at 1053 cm-1 were split into 3 peaks: 1060, 1051, 1045 cm-1. Hence by PCA, shoulders were characterized in biological solutions and more distinct peaks could be observed. These split and shift phenomena are similar to those obtained when crystalline sugar salts were investigated. This type of interaction, involving potassium ions and sucrose molecules, would be responsible for the storage of this cation which role is essential in plant metabolism.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{cadet1996baseline,
title = {Baseline correction applied to a biological: Mid-infrared spectra collection},
author = {Frédéric Cadet and Bernard Offmann},
url = {https://doi.org/10.1080/00387019608007054},
doi = {10.1080/00387019608007054},
year  = {1996},
date = {1996-01-01},
journal = {Spectroscopy letters},
volume = {29},
number = {4},
pages = {591--607},
publisher = {Taylor & Francis Group},
abstract = {Near Infrared reflectance spectroscopy is now widely applied to predict the composition of various food products. On the other hand, in only few cases have Mid-infrared spectroscopy been reported to be used for the analysis of food products. However, this range is being more and more studied and important developments are being made. In infrared spectroscopy, random variations are often observed, adding an arbitrary constant to every absorbance value. With the aim of quantifying with the best precision obtainable, it is important that such spectra are corrected. The mean and the standard deviation of the absorbance at each wavelength has been calculated from a collection of biological spectra. The spectral regions where the standard deviation values were close to or equal to zero and which correspond to the most invariable zone have been chosen as reference. Uncertain variations from a sample spectrum are corrected by translation of the whole spectrum with respect to the mean reference spectrum. The 2092–2111.28 cm-1 zone has thus been chosen as reference zone. The corrected spectrum is obtained by: where Sc is the corrected spectrum, S the initial spectrum and cst is the difference in absorbance between the reference zone and the corresponding zone in the spectrum that is to be corrected. These constants vary between -1.14×10−3 and 5.35×10−3 Predictions have been established by Principal Component Regression on MIR spectra. It follows that the precision of the predicted values are sensibly improved. The bias values for the families of spectra that have not been corrected and that have been corrected are respectively -0.0637 and -0.0045 while the standard deviation values (SD) are 0.293 and 0.247 respectively. Such an automatic baseline correction method offers considerable advantages in cases where the precision of the quantitative measurements is primordial.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@article{cadet1996gram,
title = {Gram-Schmidt Orthogonalization and Elimination of the Effect of Unwanted Component Spectra Applied to a Biological Mid-infrared Spectra Collection},
author = {Frédéric Cadet and Bernard Offmann},
url = {https://doi.org/10.1080/00387019608001620},
doi = {10.1080/00387019608001620},
year  = {1996},
date = {1996-01-01},
journal = {Spectroscopy letters},
volume = {29},
number = {5},
pages = {901--918},
publisher = {Taylor & Francis},
abstract = {Near Infrared spectroscopy (NIR) is the most widely used technique for the analysis of major biochemical constituents in food products. The Mid-infrared range spectroscopy is also being more and more studied in the field of food analysis. This range was primarily applied to qualitative analysis of food components, but with the advent of new techniques such as Attenuated Total Reflectance (ATR) together with the possibility of combination with powerful micro-computers, MIR is now more and more used for quantitative analysis. In addition to baseline deformations, interference by unwanted compounds are major sources of problems that are encountered in analyses. We have previously proposed (Cadet et al., 1991) the use of multidimensional statistical analysis combined with Mid-FTIR spectroscopy for the prediction of sucrose concentrations in biological solutions containing three sugars: sucrose, fructose and glucose. In this paper, a least-squares method has been used to assess the elimination of the component spectra associated to the fructose (the unwanted components were first orthogonal zed and normalized by the Gram-Schmidt orthogonalization method). This procedure permitted the automatic subtraction of discriminant spectral patterns representative of fructose concentration before application of Principal Component Analysis (PCA) and Principal Component Regression (PCR). PCA was applied independently before and after spectral correction of the collections. It is found that when the factorial maps obtained before and after correction are compared, the elimination procedure improves significantly the classification of solutions according to their sucrose content. However the bias and standard deviation (SD) values that are associated with the sucrose content predicted values are not influenced by the correction method used: bias and SD are 3.62×10−2 and 3.097×10−1 before correction and after correction they were respectively 3.60×10−2 and 3.104×10−1. This could be explained by the fact that the presence of fructose in solution does not interfere with caracteristic absorption bands of sucrose and that sucrose and fructose concentrations are strongly correlated. The absorbtions bands of the spectral representation of the principal component, which is identified to be that associated with sucrose, are identical before and after correction.},
keywords = {out_lab},
pubstate = {published},
tppubtype = {article}
}
@proceedings{nokey,
title = {[No title]},
url = {https://www.mdpi.com/2079-6374/14/1/43
},
doi = {doi.org/10.3390/bios14010043},
keywords = {impact, team 3},
pubstate = {published},
tppubtype = {proceedings}
}
@proceedings{nokey,
title = {[No title]},
isbn = {9782807302884},
keywords = {},
pubstate = {published},
tppubtype = {proceedings}
}