Publications

@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},

journal = {Microbiol Resour Announc .},

volume = {-},

number = {-},

issue = {-},

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 = {},

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 = {},

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'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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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',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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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+ > 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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

pubstate = {published},

tppubtype = {article}

}

@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 = {},

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 = {},

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 = {},

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 = {},

pubstate = {published},

tppubtype = {article}

}

@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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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'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 = {},

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 = {},

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 = {},

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 = {},

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 (>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 = {},

pubstate = {published},

tppubtype = {article}

}

@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 = {},

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 = {},

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 = {},

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-α 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 = {},

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 ≤ 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 ± boost and ± androgen deprivation therapy (ADT). The primary endpoint was biochemical relapse-free survival (BR-FS), defined as a PSA increase ≥ 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 = {},

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 = {},

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 = {},

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'-diisothiocyanostilbene-2,2'-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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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'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 = {},

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 = {},

pubstate = {published},

tppubtype = {article}

}

@article{<LineBreak>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 = {},

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; * < 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 = {},

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 = {},

pubstate = {published},

tppubtype = {article}

}

@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 = {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 = {},

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 = {},

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 = {},

pubstate = {published},

tppubtype = {article}

}

@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 = {},

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 = {},

pubstate = {published},

tppubtype = {article}

}

@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'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 = {},

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 = {},

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 = {},

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 = {},

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 ( < 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,  < 0.01) and a higher rate of mild infections during RT (HR = 403.5,  < 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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

pubstate = {published},

tppubtype = {article}

}

@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'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 = {},

pubstate = {published},

tppubtype = {article}

}

@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 = {},

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 = {},

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 = {},

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 = {},

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’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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

pubstate = {published},

tppubtype = {article}

}

@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 = {},

pubstate = {published},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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'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 = {},

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 = {},

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 = {},

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 = {},

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'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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

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 = {},

pubstate = {published},

tppubtype = {article}

}

@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 = {},

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' 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') input to bistable (subpopulation-specific or ‘digital') output. The feedback loop further enables prolonged production of BisDC, which ensures expression of the ‘downstream' 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 = {},

pubstate = {published},

tppubtype = {article}

}

@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 = {},

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 = {},

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 = {},

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 = {},

pubstate = {published},

tppubtype = {article}

}