Publications

@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},

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{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},

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{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},

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{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},

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{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},

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{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 S. 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{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},

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},

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 C Charlier and F Martins and S F Sousa and M Métifiot and P 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},

doi = {10.1007/s00239-023-10116-1},

year  = {2023},

date = {2023-05-23},

urldate = {2022-09-22},

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{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{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/early/2023/04/11/2023.04.11.536264},

doi = {10.1101/2023.04.11.536264},

year  = {2023},

date = {2023-04-11},

urldate = {2023-04-11},

journal = {bioRxiv},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Flavonoids glycosylation at different positions is paramount to solubility and modulation of bioactivities. Sucrose phosphorylases, through transglycosylation reactions, are interesting enzymes that can transfer glucose from sucrose, the donor substrate, onto polyphenols to form glycoconjugates. Here, we report for the first time the structural and enzymatic properties of sucrose phosphorylase from the marine bacteria Alteromonas mediterranea (AmSP). We characterized and investigated the transglucosylation capacity of two new variants of the enzyme on (+)-catechin and their propensity to catalyse its regioselective glucosylation. AmSP-Q353F and AmSP-P140D were shown to catalyse the regiospecific glucosylation of (+)-catechin using sucrose as donor substrate. While AmSP-WT was devoid of synthetic activity, each of its two single mutant provided high yields of specific regioisomers: 89% of (+)-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 novel compound CAT-4’ was fully characterized by NMR and mass spectrometry. We used molecular docking simulations on structural models of the glucosyl-enzyme intermediate to explain this regioselectivity. We showed that AmSP-P140D preferentially binds (+)-catechin in a mode that favours glucosylation on its hydroxyl group in position 4’ (OH-4’) while the binding mode of the flavonoid in AmSP-Q353F favoured glucosylation on its hydroxyl group in position 3’ (OH-3’).Competing Interest StatementThe authors have declared no competing interest.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Téletchéa2023,

title = {Evaluation of Transmembrane Protein Structural Models Using HPMScore },

author = {Stéphane Téletchéa and Jérémy Esque and Aurélie Urbain and Catherine Etchebest and Alexandre de Brevern},

editor = {Pentti Nieminen},

url = {https://www.mdpi.com/2673-7426/3/2/21},

doi = {10.3390/biomedinformatics3020021},

issn = {2673-7426},

year  = {2023},

date = {2023-04-06},

urldate = {2023-04-06},

journal = {BioMedInformatics},

volume = {3},

issue = {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},

doi = {10.1002/chem.202203497},

isbn = {1521-3765},

year  = {2023},

date = {2023-03-13},

urldate = {2023-01-01},

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/},

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},

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},

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},

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},

doi = {10.1016/j.biteb.2023.101335},

issn = {2589-014X},

year  = {2023},

date = {2023-01-13},

urldate = {2023-01-01},

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{<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{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},

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},

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{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},

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{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{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},

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},

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},

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},

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},

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},

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},

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{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},

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},

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{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{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},

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{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},

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/},

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},

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},

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{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},

doi = {10.3390/cancers14071765},

issn = {2072-6694},

year  = {2022},

date = {2022-03-30},

urldate = {2022-01-01},

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{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{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},

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{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},

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},

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},

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{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{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},

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{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},

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{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{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{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{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{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{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{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{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{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{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},

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{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},

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{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{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{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{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{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},

doi = {10.7554/eLife.57915},

issn = {2050084X},

year  = {2020},

date = {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}

}

@article{Storozhylova2020,

title = {An In Situ Hyaluronic Acid-Fibrin Hydrogel Containing Drug-Loaded Nanocapsules for Intra-Articular Treatment of Inflammatory Joint Diseases},

author = {Nataliya Storozhylova and José Crecente-Campo and David Cabaleiro and Luis Lugo and Christophe Dussouy and Sandra Sim{õ}es and Madalena Monteiro and Cyrille Grandjean and María J Alonso},

doi = {10.1007/s40883-020-00154-2},

issn = {23644141},

year  = {2020},

date = {2020-01-01},

journal = {Regenerative Engineering and Translational Medicine},

volume = {6},

number = {2},

pages = {201--216},

publisher = {Regenerative Engineering and Translational Medicine},

abstract = {Abstract: Intra-articular (IA) administration of drugs is an appealing route for the effective treatment of large-joint diseases. However, a key limitation of this route is the premature elimination of the injected drugs from the synovial cavity. The objective of this work was to develop an easily injectable controlled release system intended to prolong the activity of anti-inflammatory drugs in the articular cavity. The system was an in situ forming hydrogel, made of fibrin and hyaluronic acid (HA), loaded with nanocapsules (NCs). The NCs, consisting of an olive oil core surrounded by a HA shell, were loaded with two different drugs, dexamethasone (DMX) and a galectin-3 inhibitor. They presented a particle size in the range of 122–135 nm and a surface charge of − 29/− 31 mV. The gelation time, rheological properties and porosity of the system could be adjusted by different parameters, such as addition of fibrin crosslinkers factor XIII and α2-antiplasmin. The non-crosslinked HA-fibrin hydrogels containing 30% (v/v) NCs showed the capacity to control the release of the encapsulated drug, DMX, for 72 h in simulated synovial fluid. The preliminary in vivo evaluation of the system containing a galectin-3 inhibitor in an acute synovitis rat model showed a suppression of inflammation after IA administration compared with the non-treated control. In brief, this work shows the possibility to combine an in situ forming hydrogel and NCs as a drug delivery strategy for IA administration and suggests its potential for the treatment of arthropathies. Lay Summary: This work describes the development and characterization of a new in situ forming hydrogel adapted for intra-articular administration of anti-inflammatory drugs. The prolonged local delivery of these drugs is expected to improve the treatment of large-joint arthropathies. To achieve this objective, the hydrogel, made of biodegradable materials, was loaded with nanodeposits of drugs, named nanocapsules. The efficacy of the system, containing a new galectin-3 inhibitor as a drug candidate, was tested in a rat model of acute synovial inflammation. These results represent the first insights on the in vivo activity of a new galectin-3 inhibitor on a potential galectin-3 immunotherapeutic target for inflammatory joints diseases. [Figure not available: see fulltext.]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Teze2020,

title = {A Single Point Mutation Converts GH84 O-GlcNAc Hydrolases into Phosphorylases: Experimental and Theoretical Evidence},

author = {David Teze and Joan Coines and Lluís Raich and Valentina Kalichuk and Claude Solleux and Charles Tellier and Corinne André-Miral and Birte Svensson and Carme Rovira},

doi = {10.1021/jacs.9b09655},

issn = {15205126},

year  = {2020},

date = {2020-01-01},

journal = {Journal of the American Chemical Society},

volume = {142},

number = {5},

pages = {2120--2124},

abstract = {Glycoside hydrolases and phosphorylases are two major classes of enzymes responsible for the cleavage of glycosidic bonds. Here we show that two GH84 O-GlcNAcase enzymes can be converted to efficient phosphorylases by a single point mutation. Noteworthy, the mutated enzymes are over 10-fold more active than naturally occurring glucosaminide phosphorylases. We rationalize this novel transformation using molecular dynamics and QM/MM metadynamics methods, showing that the mutation changes the electrostatic potential at the active site and reduces the energy barrier for phosphorolysis by 10 kcaltextperiodcenteredmol-1. In addition, the simulations unambiguously reveal the nature of the intermediate as a glucose oxazolinium ion, clarifying the debate on the nature of such a reaction intermediate in glycoside hydrolases operating via substrate-assisted catalysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{violo:hal-02990572,

title = {Homogenous Glycoconjugate Produced by Combined Unnatural Amino Acid Incorporation and Click-Chemistry for Vaccine Purposes},

author = {Typhaine Violo and Christophe Dussouy and Charles Tellier and Cyrille Grandjean and Emilie Camberlein},

url = {https://hal.archives-ouvertes.fr/hal-02990572},

doi = {10.3791/60821},

year  = {2020},

date = {2020-01-01},

journal = {Journal of visualized experiments : JoVE},

publisher = {JoVE},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Visnapuu2020,

title = {Identification and characterization of a β-n-acetylhexosaminidase with a biosynthetic activity from the marine bacterium paraglaciecola hydrolytica S66T},

author = {Triinu Visnapuu and David Teze and Christian Kjeldsen and Aleksander Lie and Jens Øllgaard Duus and Corinne André-Miral and Lars Haastrup Pedersen and Peter Stougaard and Birte Svensson},

doi = {10.3390/ijms21020417},

issn = {14220067},

year  = {2020},

date = {2020-01-01},

journal = {International Journal of Molecular Sciences},

volume = {21},

number = {2},

publisher = {MDPI AG},

abstract = {β-N-Acetylhexosaminidases are glycoside hydrolases (GHs) acting on N-acetylated carbohydrates and glycoproteins with the release of N-acetylhexosamines. Members of the family GH20 have been reported to catalyze the transfer of N-acetylglucosamine (GlcNAc) to an acceptor, i.e., the reverse of hydrolysis, thus representing an alternative to chemical oligosaccharide synthesis. Two putative GH20 β-N-acetylhexosaminidases, PhNah20A and PhNah20B, encoded by the marine bacterium Paraglaciecola hydrolytica S66T, are distantly related to previously characterized enzymes. Remarkably, PhNah20A was located by phylogenetic analysis outside clusters of other studied β-N-acetylhexosaminidases, in a unique position between bacterial and eukaryotic enzymes. We successfully produced recombinant PhNah20A showing optimum activity at pH 6.0 and 50◦C, hydrolysis of GlcNAc β-1,4 and β-1,3 linkages in chitobiose (GlcNAc)2 and GlcNAc-1,3-β-Gal-1,4-β-Glc (LNT2), a human milk oligosaccharide core structure. The kinetic parameters of PhNah20A for p-nitrophenyl-GlcNAc and p-nitrophenyl-GalNAc were highly similar: kcat /KM being 341 and 344 mM−1 s−1, respectively. PhNah20A was unstable in dilute solution, but retained full activity in the presence of 0.5% bovine serum albumin (BSA). PhNah20A catalyzed the formation of LNT2, the non-reducing trisaccharide β-Gal-1,4-β-Glc-1,1-β-GlcNAc, and in low amounts the β-1,2-or β-1,3-linked trisaccharide β-Gal-1,4(β-GlcNAc)-1,x-Glc by a transglycosylation of lactose using 2-methyl-(1,2-dideoxy-α-d-glucopyrano)-oxazoline (NAG-oxazoline) as the donor. PhNah20A is the first characterized member of a distinct subgroup within GH20 β-N-acetylhexosaminidases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.3389/fnagi.2020.00103,

title = {Resveratrol Derivatives as Potential Treatments for Alzheimer’s and Parkinson’s Disease},

author = {Bruno Dutra Arbo and Corinne André-Miral and Raif Gregorio Nasre-Nasser and Lúcia Emanueli Schimith and Michele Goulart Santos and Dennis Costa-Silva and Ana Luiza Muccillo-Baisch and Mariana Appel Hort},

url = {https://www.frontiersin.org/article/10.3389/fnagi.2020.00103},

doi = {10.3389/fnagi.2020.00103},

issn = {1663-4365},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Frontiers in Aging Neuroscience},

volume = {12},

pages = {103},

abstract = {Neurodegenerative diseases are characterized by the progressive loss of neurons in different regions of the nervous system. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most prevalent neurodegenerative diseases, and the symptoms associated with these pathologies are closely related to the regions that are most affected by the process of neurodegeneration. Despite their high prevalence, currently, there is no cure or disease-modifying drugs for the treatment of these conditions. In the last decades, due to the need for the development of new treatments for neurodegenerative diseases, several authors have investigated the neuroprotective actions of naturally occurring molecules, such as resveratrol. Resveratrol is a stilbene found in several plants, including grapes, blueberries, raspberries, and peanuts. Studies have shown that resveratrol presents neuroprotective actions in experimental models of AD and PD, however, its clinical application is limited due to its rapid metabolism and low bioavailability. In this context, studies have proposed that structural changes in the resveratrol molecule, including glycosylation, alkylation, halogenation, hydroxylation, methylation, and prenylation could lead to the development of derivatives with enhanced bioavailability and pharmacological activity. Therefore, this review article aims to discuss how resveratrol derivatives could represent viable molecules in the search for new drugs for the treatment of AD and PD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1021/acs.joc.0c01927b,

title = {Access to Galectin-3 Inhibitors from Chemoenzymatic Synthons},

author = {Christophe Dussouy and Stéphane Téletchéa and Annie Lambert and Cathy Charlier and Iuliana Botez and Frédéric De Ceuninck and Cyrille Grandjean},

url = {https://doi.org/10.1021/acs.joc.0c01927},

doi = {10.1021/acs.joc.0c01927},

year  = {2020},

date = {2020-01-01},

journal = {The Journal of Organic Chemistry},

volume = {85},

number = {24},

pages = {16099-16114},

abstract = {Chemoenzymatic strategies are useful for providing both regio- and stereoselective access to bioactive oligosaccharides. We show herein that a glycosynthase mutant of a Thermus thermophilus α-glycosidase can react with unnatural glycosides such as 6-azido-6-deoxy-d-glucose/glucosamine to lead to β-d-galactopyranosyl-(1→3)-d-glucopyranoside or β-d-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-d-glucopyranoside derivatives bearing a unique azide function. Taking advantage of the orthogonality between the azide and the hydroxyl functional groups, the former was next selectively reacted to give rise to a library of galectin-3 inhibitors. Combining enzyme substrate promiscuity and bioorthogonality thus appears as a powerful strategy to rapidly access to sugar-based ligands},

note = {PMID: 33200927},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Yaremenko2020a,

title = {Catalyst Development for the Synthesis of Ozonides and Tetraoxanes Under Heterogeneous Conditions: Disclosure of an Unprecedented Class of Fungicides for Agricultural Application},

author = {Ivan A Yaremenko and Peter S Radulov and Yulia Yu Belyakova and Arina A Demina and Dmitriy I Fomenkov and Denis V Barsukov and Irina R Subbotina and Fabrice Fleury and Alexander O Terent'ev},

doi = {10.1002/chem.201904555},

issn = {15213765},

year  = {2020},

date = {2020-01-01},

journal = {Chemistry - A European Journal},

volume = {26},

number = {21},

pages = {4734--4751},

abstract = {The catalyst H3+xPMo12−x+6Mox+5O40 supported on SiO2 was developed for peroxidation of 1,3- and 1,5-diketones with hydrogen peroxide with the formation of bridged 1,2,4,5-tetraoxanes and bridged 1,2,4-trioxolanes (ozonides) with high yield based on isolated products (up to 86 and 90 %, respectively) under heterogeneous conditions. Synthesis of peroxides under heterogeneous conditions is a rare process and represents a challenge for this field of chemistry, because peroxides tend to decompose on the surface of a catalyst. A new class of antifungal agents for crop protection, that is, cyclic peroxides: bridged 1,2,4,5-tetraoxanes and bridged ozonides, was discovered. Some ozonides and tetraoxanes exhibit a very high antifungal activity and are superior to commercial fungicides, such as Triadimefon and Kresoxim-methyl. It is important to note that none of the fungicides used in agricultural chemistry contains a peroxide fragment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{LAFONT2020129705,

title = {DNA-PKcs Ser2056 auto-phosphorylation is affected by an O-GlcNAcylation/phosphorylation interplay},

author = {Florian Lafont and Fabrice Fleury and Houda Benhelli-Mokrani},

url = {http://www.sciencedirect.com/science/article/pii/S0304416520302178},

doi = {https://doi.org/10.1016/j.bbagen.2020.129705},

issn = {0304-4165},

year  = {2020},

date = {2020-01-01},

journal = {Biochimica et Biophysica Acta (BBA) - General Subjects},

volume = {1864},

number = {12},

pages = {129705},

abstract = {Background DNA dependent Protein Kinase (DNA-PK) is an heterotrimeric complex regulating the Non Homologous End Joining (NHEJ) double strand break (DSB) repair pathway. The activity of its catalytic subunit (DNA-PKcs) is regulated by multiple phosphorylations, like the Ser2056 one that impacts DSB end processing and telomeres integrity. O-GlcNAcylation is a post translational modification (PTM) closely related to phosphorylation and its implication in the modulation of DNA-PKcs activity during the DNA Damage Response (DDR) is unknown. Methods Using IP techniques, and HeLa cell line, we evaluated the effect of pharmacological or siOGT mediated O-GlcNAc level modulation on DNA-PKcs O-GlcNAcylation. We used the RPA32 phosphorylation as a DNA-PKcs activity reporter substrate to evaluate the effect of O-GlcNAc modulators. Results We show here that human DNA-PKcs is an O-GlcNAc modified protein and that this new PTM is responsive to the cell O-GlcNAcylation level modulation. Our findings reveal that DNA-PKcs hypo O-GlcNAcylation affects its kinase activity and that the bleomycin-induced Ser2056 phosphorylation, is modulated by DNA-PKcs O-GlcNAcylation. Conclusions DNA-PKcs Ser2056 phosphorylation is antagonistically linked to DNA-PKcs O-GlcNAcylation level modulation. General significance Given the essential role of DNA-PKcs Ser2056 phosphorylation in the DDR, this study brings data about the role of cell O-GlcNAc level on genome integrity maintenance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vil2020,

title = {Ion exchange resin-catalyzed synthesis of bridged tetraoxanes possessing in vitro cytotoxicity against HeLa cancer cells},

author = {Vera A Vil' and Ivan A Yaremenko and Dmitri I Fomenkov and Dmitri O Levitsky and Fabrice Fleury and Alexander O Terent'ev},

url = {https://doi.org/10.1007/s10593-020-02722-4},

doi = {10.1007/s10593-020-02722-4},

issn = {1573-8353},

year  = {2020},

date = {2020-01-01},

journal = {Chemistry of Heterocyclic Compounds},

volume = {56},

number = {6},

pages = {722--726},

abstract = {Bridged 1,2,4,5-tetraoxanes were prepared using available acidic ion exchange resin with high yields despite the possibility of peroxide decomposition under heterogeneous conditions. The bridged tetraoxanes demonstrated high cytotoxicity against HeLa cancer cells in vitro, which in some cases was higher than that of cisplatin, artesunate, and dihydroartemisinin.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32765559,

title = {Populations of the Parasitic Plant  Influence Their Seed Microbiota},

author = {Sarah Huet and Jean-Bernard Pouvreau and Erwan Delage and Sabine Delgrange and Coralie Marais and Muriel Bahut and Philippe Delavault and Philippe Simier and Lucie Poulin},

doi = {10.3389/fpls.2020.01075},

issn = {1664-462X},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Front Plant Sci},

volume = {11},

pages = {1075},

abstract = {Seeds of the parasitic weed  are well adapted to their hosts because they germinate and form haustorial structures to connect to roots in response to diverse host-derived molecular signals.  presents different genetic groups that are preferentially adapted to certain hosts. Since there are indications that microbes play a role in the interaction especially in the early stages of the interaction, we studied the microbial diversity harbored by the parasitic seeds with respect to their host and genetic group. Twenty-six seed lots from seven cropping plots of three different hosts-oilseed rape, tobacco, and hemp-in the west of France were characterized for their bacterial and fungal communities using 16S rRNA gene and ITS (Internal transcribed spacer) sequences, respectively. First seeds were characterized genetically using twenty microsatellite markers and phenotyped for their sensibility to various germination stimulants including strigolactones and isothiocyanates. This led to the distinction of three  groups that corresponded to their host of origin. The observed seed diversity was correlated to the host specialization and germination stimulant sensitivity within  species. Microbial communities were both clustered by host and plot of origin. The seed core microbiota was composed of seventeen species that were also retrieved from soil and was in lower abundances for bacteria and similar abundances for fungi compared to seeds. The host-related core microbiota of parasitic seeds was limited and presumably well adapted to the interaction with its hosts. Two microbial candidates of  species and  were especially identified in seeds from oilseed rape plots, suggesting their involvement in host recognition and specialization as well as seed fitness for  by improving the production of isothiocyanates from glucosinolates in the rhizosphere of oilseed rape.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN2,

title = {Are root parasitic plants like any other plant pathogens?},

author = {Philippe Delavault},

url = {https://nph.onlinelibrary.wiley.com/doi/10.1111/nph.16504},

doi = {10.1111/nph.16504},

issn = {0028-646x},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {New Phytol},

volume = {226},

number = {3},

pages = {641-643},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN31,

title = {Correction to: Cytokinin treated microcalli of Phelipanche ramosa: an efficient model for studying haustorium formation in holoparasitic plants},

author = {Estelle Billard and Vincent Goyet and Philippe Delavault and Philippe Simier and Grégory Montiel},

url = {https://doi.org/10.1007/s11240-020-01832-3 

https://link.springer.com/content/pdf/10.1007/s11240-020-01832-3.pdf},

doi = {10.1007/s11240-020-01832-3},

issn = {1573-5044},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Plant Cell, Tissue and Organ Culture (PCTOC)},

volume = {141},

number = {3},

pages = {555-555},

abstract = {The caption to Fig. 4 belonged to Fig. 5 and vice versa in the initial online publication. The original article has been corrected.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3,

title = {Management of Infection by Parasitic Weeds: A Review},

author = {Monica Fernández-Aparicio and Philippe Delavault and Michael Timko},

url = {https://mdpi-res.com/d_attachment/plants/plants-09-01184/article_deploy/plants-09-01184.pdf},

doi = {10.3390/plants9091184},

issn = {2223-7747 (Print) 2223-7747},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Plants (Basel)},

volume = {9},

number = {9},

abstract = {Parasitic plants rely on neighboring host plants to complete their life cycle, forming vascular connections through which they withdraw needed nutritive resources. In natural ecosystems, parasitic plants form one component of the plant community and parasitism contributes to overall community balance. In contrast, when parasitic plants become established in low biodiversified agroecosystems, their persistence causes tremendous yield losses rendering agricultural lands uncultivable. The control of parasitic weeds is challenging because there are few sources of crop resistance and it is difficult to apply controlling methods selective enough to kill the weeds without damaging the crop to which they are physically and biochemically attached. The management of parasitic weeds is also hindered by their high fecundity, dispersal efficiency, persistent seedbank, and rapid responses to changes in agricultural practices, which allow them to adapt to new hosts and manifest increased aggressiveness against new resistant cultivars. New understanding of the physiological and molecular mechanisms behind the processes of germination and haustorium development, and behind the crop resistant response, in addition to the discovery of new targets for herbicides and bioherbicides will guide researchers on the design of modern agricultural strategies for more effective, durable, and health compatible parasitic weed control.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sato2020,

title = {Genome-enabled phylogenetic and functional reconstruction of an araphid pennate diatom Plagiostriata sp. CCMP470, previously assigned as a radial centric diatom, and its bacterial commensal},

author = {Shinya Sato and Deepak Nanjappa and Richard G Dorrell and Fabio Rocha Jimenez Vieira and Elena Kazamia and Leila Tirichine and Alaguraj Veluchamy and Roland Heilig and Jean Marc Aury and Olivier Jaillon and Patrick Wincker and Zoltan Fussy and Miroslav Obornik and Sergio A Mu{ñ}oz-Gómez and David G Mann and Chris Bowler and Adriana Zingone},

doi = {10.1038/s41598-020-65941-x},

issn = {20452322},

year  = {2020},

date = {2020-01-01},

journal = {Scientific Reports},

volume = {10},

number = {1},

pages = {1--12},

abstract = {Diatoms are an ecologically fundamental and highly diverse group of algae, dominating marine primary production in both open-water and coastal communities. The diatoms include both centric species, which may have radial or polar symmetry, and the pennates, which include raphid and araphid species and arose within the centric lineage. Here, we use combined microscopic and molecular information to reclassify a diatom strain CCMP470, previously annotated as a radial centric species related to Leptocylindrus danicus, as an araphid pennate species in the staurosiroid lineage, within the genus Plagiostriata. CCMP470 shares key ultrastructural features with Plagiostriata taxa, such as the presence of a sternum with parallel striae, and the presence of a highly reduced labiate process on its valve; and this evolutionary position is robustly supported by multigene phylogenetic analysis. We additionally present a draft genome of CCMP470, which is the first genome available for a staurosiroid lineage. 270 Pfams (19%) found in the CCMP470 genome are not known in other diatom genomes, which otherwise does not hold big novelties compared to genomes of non-staurosiroid diatoms. Notably, our DNA library contains the genome of a bacterium within the Rhodobacterales, an alpha-proteobacterial lineage known frequently to associate with algae. We demonstrate the presence of commensal alpha-proteobacterial sequences in other published algal genome and transcriptome datasets, which may indicate widespread and persistent co-occurrence.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{rastogi2020genomics,

title = {A genomics approach reveals the global genetic polymorphism, structure, and functional diversity of ten accessions of the marine model diatom Phaeodactylum tricornutum},

author = {Achal Rastogi and Fabio Rocha Jimenez Vieira and Anne-Flore Deton-Cabanillas and Alaguraj Veluchamy and Catherine Cantrel and Gaohong Wang and Pieter Vanormelingen and Chris Bowler and Gwenael Piganeau and Hanhua Hu and Others},

doi = {https://doi.org/10.1038/s41396-019-0528-3},

year  = {2020},

date = {2020-01-01},

journal = {The ISME journal},

volume = {14},

number = {2},

pages = {347--363},

publisher = {Nature Publishing Group},

abstract = {Diatoms emerged in the Mesozoic period and presently constitute one of the main primary producers in the world's ocean and are of a major economic importance. In the current study, using whole genome sequencing of ten accessions of the model diatom Phaeodactylum tricornutum, sampled at broad geospatial and temporal scales, we draw a comprehensive landscape of the genomic diversity within the species. We describe strong genetic subdivisions of the accessions into four genetic clades (A–D) with constituent populations of each clade possessing a conserved genetic and functional makeup, likely a consequence of the limited dispersal of P. tricornutum in the open ocean. We further suggest dominance of asexual reproduction across all the populations, as implied by high linkage disequilibrium. Finally, we show limited yet compelling signatures of genetic and functional convergence inducing changes in the selection pressure on many genes and metabolic pathways. We propose these findings to have significant implications for understanding the genetic structure of diatom populations in nature and provide a framework to assess the genomic underpinnings of their ecological success and impact on aquatic ecosystems where they play a major role. Our work provides valuable resources for functional genomics and for exploiting the biotechnological potential of this model diatom species.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fan2020,

title = {Single-base methylome profiling of the giant kelp Saccharina japonica reveals significant differences in DNA methylation to microalgae and plants},

author = {Xiao Fan and Wentao Han and Linhong Teng and Peng Jiang and Xiaowen Zhang and Dong Xu and Chang Li and Matteo Pellegrini and Chunhui Wu and Yitao Wang and Michelle Joyce Slade Kaczurowski and Xin Lin and Leila Tirichine and Thomas Mock and Naihao Ye},

doi = {10.1111/nph.16125},

issn = {14698137},

year  = {2020},

date = {2020-01-01},

journal = {New Phytologist},

volume = {225},

number = {1},

pages = {234--249},

abstract = {Brown algae have convergently evolved plant-like body plans and reproductive cycles, which in plants are controlled by differential DNA methylation. This contribution provides the first single-base methylome profiles of haploid gametophytes and diploid sporophytes of a multicellular alga. Although only c. 1.4% of cytosines in Saccharina japonica were methylated mainly at CHH sites and characterized by 5-methylcytosine (5mC), there were significant differences between life-cycle stages. DNA methyltransferase 2 (DNMT2), known to efficiently catalyze tRNA methylation, is assumed to methylate the genome of S. japonica in the structural context of tRNAs as the genome does not encode any other DNA methyltransferases. Circular and long noncoding RNA genes were the most strongly methylated regulatory elements in S. japonica. Differential expression of genes was negatively correlated with DNA methylation with the highest methylation levels measured in both haploid gametophytes. Hypomethylated and highly expressed genes in diploid sporophytes included genes involved in morphogenesis and halogen metabolism. The data herein provide evidence that cytosine methylation, although occurring at a low level, is significantly contributing to the formation of different life-cycle stages, tissue differentiation and metabolism in brown algae.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.3389/fmars.2020.00189,

title = {Probing the Diversity of Polycomb and Trithorax Proteins in Cultured and Environmentally Sampled Microalgae},

author = {Xue Zhao and Anne Flore {Deton Cabanillas} and Alaguraj Veluchamy and Chris Bowler and Fabio Rocha Jimenez Vieira and Leila Tirichine},

url = {https://www.frontiersin.org/article/10.3389/fmars.2020.00189},

doi = {10.3389/fmars.2020.00189},

issn = {2296-7745},

year  = {2020},

date = {2020-01-01},

journal = {Frontiers in Marine Science},

volume = {7},

pages = {189},

abstract = {Polycomb (PcG) and Trithorax (TrxG) complexes are two evolutionarily conserved epigenetic regulatory components that act antagonistically to regulate the expression of genes involved in cell differentiation and development in multicellular organisms. The absence of PcG in both yeast models Saccharomyces cerevisiae and Schizosaccharomyces pombe suggested that polycomb proteins might have evolved together with the emergence of multicellular organisms. However, high throughput sequencing of several microalgal genomes and transcriptomes reveals an unprecedented abundance and diversity of genes encoding the components of these complexes. We report here the diversity of genes encoding PcG and TrxG proteins in microalgae from the Marine Microbial Eukaryote Transcriptome Sequencing Project database (MMETSP) and detected at broad scale in Tara Oceans genomics datasets using a highly sensitive method called eDAF (enhanced Domain Architecture Filtering). Further, we explored the correlation between environmental factors measured during the Tara Oceans expedition and transcript levels of PcG and TrxG components. PcG and TrxG are responsible for the deposition of a number of histone marks among which a TrxG associated mark, H3K4me3 which we profiled genome wide in the model diatom Phaeodactylum tricornutum to understand its role in microalgae and revisited the previously published histone code and co-occurrence with other histone marks including the antagonizing Polycomb deposited mark H3K27me3.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{plants9111508,

title = {Low Mannitol Concentrations in Arabidopsis thaliana Expressing Ectocarpus Genes Improve Salt Tolerance},

author = {Pramod Rathor and Tudor Borza and Yanhui Liu and Yuan Qin and Sophia Stone and Junzeng Zhang and Joseph P M Hui and Fabrice Berrue and Agnès Groisillier and Thierry Tonon and Svetlana Yurgel and Philippe Potin and Balakrishnan Prithiviraj},

url = {https://www.mdpi.com/2223-7747/9/11/1508},

doi = {10.3390/plants9111508},

issn = {2223-7747},

year  = {2020},

date = {2020-01-01},

journal = {Plants},

volume = {9},

number = {11},

abstract = {Mannitol is abundant in a wide range of organisms, playing important roles in biotic and abiotic stress responses. Nonetheless, mannitol is not produced by a vast majority of plants, including many important crop plants. Mannitol-producing transgenic plants displayed improved tolerance to salt stresses though mannitol production was rather low, in the µM range, compared to mM range found in plants that innately produce mannitol. Little is known about the molecular mechanisms underlying salt tolerance triggered by low concentrations of mannitol. Reported here is the production of mannitol in Arabidopsis thaliana, by expressing two mannitol biosynthesis genes from the brown alga Ectocarpus sp. strain Ec32. To date, no brown algal genes have been successfully expressed in land plants. Expression of mannitol-1-phosphate dehydrogenase and mannitol-1-phosphatase genes was associated with the production of 42.3-52.7 nmol g−1 fresh weight of mannitol, which was sufficient to impart salinity and temperature stress tolerance. Transcriptomics revealed significant differences in the expression of numerous genes, in standard and salinity stress conditions, including genes involved in K+ homeostasis, ROS signaling, plant development, photosynthesis, ABA signaling and secondary metabolism. These results suggest that the improved tolerance to salinity stress observed in transgenic plants producing mannitol in µM range is achieved by the activation of a significant number of genes, many of which are involved in priming and modulating the expression of genes involved in a variety of functions including hormone signaling, osmotic and oxidative stress, and ion homeostasis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{LeStrat2020.07.01.179531,

title = {Characterization of redox sensitive algal mannitol-1-phosphatases of the haloacid dehalogenase superfamily of proteins},

author = {Yoran Le Strat and Thierry Tonon and Catherine Leblanc and Agnès Groisillier},

url = {https://www.biorxiv.org/content/early/2020/07/01/2020.07.01.179531},

doi = {10.1101/2020.07.01.179531},

year  = {2020},

date = {2020-01-01},

journal = {bioRxiv},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Macroalgae (or seaweeds) are the dominant primary producers in marine vegetated coastal habitats and largely contribute to global ocean carbon fluxes. They also represent attractive renewable production platforms for biofuels, food, feed, and bioactives, notably due to their diverse and peculiar polysaccharides and carbohydrates. Among seaweeds, brown algae produce alginates and sulfated fucans as constituents of their cell wall, and the photoassimilates laminarin and mannitol for carbon storage. Availability of brown algal genomes, including those of the kelp Saccharina japonica and the filamentous Ectocarpus sp., has paved the way for biochemical characterization of recombinant enzymes involved in their polysaccharide and carbohydrates synthesis, notably mannitol. Biosynthesis of mannitol in brown algae starts from fructose-6-phospate, which is converted into mannitol-1-phosphate (M1P), and this intermediate is then hydrolysed by a haloacid dehalogenase type M1P phosphatase (M1Pase) to produce mannitol. We report here the biochemical characterization of a second M1Pase in Ectocarpus sp after heterologous expression in Escherichia coli. (EsM1Pase1). Our results show that both Ectocarpus M1Pases were redox sensitive, with EsM1Pase1 being active only in presence of reducing agent. Such catalytic properties have not been observed for any of the M1Pase characterized so far. EsM1Pases were specific to mannitol, in contrast to S. japonica M1Pases that can use other phosphorylated sugars as substrates. Finally, brown algal M1Pases grouped into two well-supported clades, with potential different subcellular localization and physiological role(s) under diverse environmental conditions and/or stages of life cycle.Competing Interest StatementThe authors have declared no competing interest.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ostafe2020,

title = {One-shot optimization of multiple enzyme parameters: Tailoring glucose oxidase for pH and electron mediators},

author = {Raluca Ostafe and Nicolas Fontaine and David Frank and Matthieu {Ng Fuk Chong} and Radivoje Prodanovic and Rudy Pandjaitan and Bernard Offmann and Frédéric Cadet and Rainer Fischer},

doi = {10.1002/bit.27169},

issn = {10970290},

year  = {2020},

date = {2020-01-01},

journal = {Biotechnology and Bioengineering},

volume = {117},

number = {1},

pages = {17--29},

abstract = {Enzymes are biological catalysts with many industrial applications, but natural enzymes are usually unsuitable for industrial processes because they are not optimized for the process conditions. The properties of enzymes can be improved by directed evolution, which involves multiple rounds of mutagenesis and screening. By using mathematical models to predict the structure–activity relationship of an enzyme, and by defining the optimal combination of mutations in silico, we can significantly reduce the number of bench experiments needed, and hence the time and investment required to develop an optimized product. Here, we applied our innovative sequence–activity relationship methodology (innov'SAR) to improve glucose oxidase activity in the presence of different mediators across a range of pH values. Using this machine learning approach, a predictive model was developed and the optimal combination of mutations was determined, leading to a glucose oxidase mutant (P1) with greater specificity for the mediators ferrocene–methanol (12-fold) and nitrosoaniline (8-fold), compared to the wild-type enzyme, and better performance in three pH-adjusted buffers. The kcat/KM ratio of P1 increased by up to 121 folds compared to the wild type enzyme at pH 5.5 in the presence of ferrocene methanol.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hendrickx2020,

title = {Numerous severely twisted N-acetylglucosamine conformations found in the protein databank},

author = {Johann Hendrickx and Vinh Tran and Yves-Henri Sanejouand},

doi = {10.1002/prot.25957},

issn = {10970134},

year  = {2020},

date = {2020-01-01},

journal = {Proteins: Structure, Function and Bioinformatics},

volume = {88},

number = {10},

pages = {1376--1383},

abstract = {Taking advantage of the known planarity of the N-acetyl group of N-acetylglucosamine, an analysis of the quality of carbohydrate structures found in the protein databank was performed. Few obvious defects of the local geometry of the carbonyl group were observed. However, the N-acetyl group was often found in the less favorable cis conformation (12% of the cases). It was also found severely twisted in numerous instances, especially in structures with a resolution poorer than 1.9 Å determined between 2000 and 2015. Though the automated PDB-REDO procedure has proved able to improve nearly 85% of the structural models deposited to the PDB, and does prove able to cure most severely twisted conformations of the N-acetyl group, it fails to correct its high rate of cis conformations. More generally, for structures with a resolution poorer than 1.6 Å, it produces N-acetylglucosamine models in slightly poorer agreement with experimental data, as measured using real-space correlation coefficients. Significant improvements are thus still needed, at least as far as this carbohydrate structure is concerned.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DHINGRA202085,

title = {A glance into the evolution of template-free protein structure prediction methodologies},

author = {Surbhi Dhingra and Ramanathan Sowdhamini and Frédéric Cadet and Bernard Offmann},

url = {http://www.sciencedirect.com/science/article/pii/S0300908420300961},

doi = {https://doi.org/10.1016/j.biochi.2020.04.026},

issn = {0300-9084},

year  = {2020},

date = {2020-01-01},

journal = {Biochimie},

volume = {175},

pages = {85 - 92},

abstract = {Prediction of protein structures using computational approaches has been explored for over two decades, paving a way for more focused research and development of algorithms in comparative modelling, ab intio modelling and structure refinement protocols. A tremendous success has been witnessed in template-based modelling protocols, whereas strategies that involve template-free modelling still lag behind, specifically for larger proteins (>150 a.a.). Various improvements have been observed in ab initio protein structure prediction methodologies overtime, with recent ones attributed to the usage of deep learning approaches to construct protein backbone structure from its amino acid sequence. This review highlights the major strategies undertaken for template-free modelling of protein structures while discussing few tools developed under each strategy. It will also briefly comment on the progress observed in the field of ab initio modelling of proteins over the course of time as seen through the evolution of CASP platform.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{catal10030291,

title = {A Machine Learning Approach for Efficient Selection of Enzyme Concentrations and Its Application for Flux Optimization},

author = {Anamya Ajjolli Nagaraja and Philippe Charton and Xavier F Cadet and Nicolas Fontaine and Mathieu Delsaut and Birgit Wiltschi and Alena Voit and Bernard Offmann and Cedric Damour and Brigitte Grondin-Perez and Frederic Cadet},

url = {https://www.mdpi.com/2073-4344/10/3/291},

doi = {10.3390/catal10030291},

issn = {2073-4344},

year  = {2020},

date = {2020-01-01},

journal = {Catalysts},

volume = {10},

number = {3},

abstract = {The metabolic engineering of pathways has been used extensively to produce molecules of interest on an industrial scale. Methods like gene regulation or substrate channeling helped to improve the desired product yield. Cell-free systems are used to overcome the weaknesses of engineered strains. One of the challenges in a cell-free system is selecting the optimized enzyme concentration for optimal yield. Here, a machine learning approach is used to select the enzyme concentration for the upper part of glycolysis. The artificial neural network approach (ANN) is known to be inefficient in extrapolating predictions outside the box: high predicted values will bump into a sort of “glass ceiling”. In order to explore this “glass ceiling” space, we developed a new methodology named glass ceiling ANN (GC-ANN). Principal component analysis (PCA) and data classification methods are used to derive a rule for a high flux, and ANN to predict the flux through the pathway using the input data of 121 balances of four enzymes in the upper part of glycolysis. The outcomes of this study are i. in silico selection of optimum enzyme concentrations for a maximum flux through the pathway and ii. experimental in vitro validation of the “out-of-the-box” fluxes predicted using this new approach. Surprisingly, flux improvements of up to 63% were obtained. Gratifyingly, these improvements are coupled with a cost decrease of up to 25% for the assay.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{liu2020comprehensive,

title = {Comprehensive History of CSP Genes: Evolution, Phylogenetic Distribution and Functions},

author = {Guoxia Liu and Ning Xuan and Balaji Rajashekar and Philippe Arnaud and Bernard Offmann and Jean-François Picimbon},

doi = {10.3390/genes11040413},

year  = {2020},

date = {2020-01-01},

journal = {Genes},

volume = {11},

number = {4},

pages = {413},

publisher = {Multidisciplinary Digital Publishing Institute},

abstract = {In this review we present the developmental, histological, evolutionary and functional properties of insect chemosensory proteins (CSPs) in insect species. CSPs are small globular proteins folded like a prism and notoriously known for their complex and arguably obscure function(s), particularly in pheromone olfaction. Here, we focus on direct functional consequences on protein function depending on duplication, expression and RNA editing. The result of our analysis is important for understanding the significance of RNA-editing on functionality of CSP genes, particularly in the brain tissue.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1093/database/baaa095,

title = {STOREFISH 2.0: a database on the reproductive strategies of teleost fishes},

author = {Stéphane Téletchéa and Fabrice Téletchéa},

url = {https://doi.org/10.1093/database/baaa095},

doi = {10.1093/database/baaa095},

issn = {1758-0463},

year  = {2020},

date = {2020-01-01},

journal = {Database},

volume = {2020},

abstract = {Teleost fishes show the most outstanding reproductive diversity of all vertebrates. Yet to date, no one has been able to decisively explain this striking variability nor to perform large-scale phylogenetic analyses of reproductive modes. Here, we describe STrategies Of REproduction in FISH (STOREFISH) 2.0, an online database easing the sharing of an original data set on reproduction published in 2007, enriched with automated data extraction and presentation to display the knowledge acquired on temperate freshwater fish species. STOREFISH 2.0 contains the information for 80 freshwater fish species and 50 traits from the analysis of 1219 references. It is anticipated that this new database could be useful for freshwater biodiversity research, conservation, assessment and management.Database URL: www.storefish.org},

note = {baaa095},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bogoeva2019,

title = {Binding of Gold(III) Porphyrin by the Pro-metastatic Regulatory Protein Human Galectin-3},

author = {Vanya Bogoeva and Miroslav Rangelov and Nadezhda Todorova and Annie Lambert and Clarisse Bridot and Anna Yordanova and Goedele Roos and Cyrille Grandjean and Julie Bouckaert},

doi = {10.3390/molecules24244561},

issn = {14203049},

year  = {2019},

date = {2019-12-01},

journal = {Molecules},

volume = {24},

number = {24},

publisher = {MDPI AG},

abstract = {Gold(III) porphyrin presents an attractive alternative to the use of, for example, cisplatin in chemotherapy. However, approaches that allow to selectively target cancer cells are highly sought. Many plant and mammalian lectins have been shown to bind oligosaccharide sequences of the aberrant glycosylation pattern found on cancerous tumors. For example human galectin-3, of the galectin family specific for ß-galactoside, is overexpressed in the extracellular matrix of tumorigenous and metastatic tissues. We searched for non-carbohydrate ligands for galectin-3 that can guide a cytotoxic drug to the cancer cells by maintaining its affinity for tumor associated carbohydrate antigens. Previous findings showed that zinc tetrasulfonatophenylporphyrin can bind galectin-3 with sub-micromolar affinity without disturbing lactose binding. Gold(III) porphyrin is not only cytotoxic to cancer cells, it knows also a potential application as photosensitiser in photodynamic therapy. We investigated the binding of gold(III) porphyrin to galectin-3 using different biophysical interaction techniques and demonstrated a low micromolar affinity of human galectin-3 for the cytotoxic compound. Co-crystallization attempts in order to understand the binding mode of gold porphyrin to galectin-3 failed, but molecular docking emphasized a highly populated secondary binding site that does not hinder lactose or Thomsen Friendenreich disaccharide binding. This suggests that gold(III) porphyrin might significantly enhance its concentration and delivery to cancer cells by binding to human galectin-3 that keeps its orientation towards tumor associated carbohydrate antigens.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31499274,

title = {Contalactone, a contaminant formed during chemical synthesis of the strigolactone reference GR24 is also a strigolactone mimic},

author = {Alexandre de Saint Germain and Pascal Retailleau and Stéphanie Norsikian and Vincent Servajean and Franck Pelissier and Vincent Steinmetz and Jean-Paul Pillot and Soizic Rochange and Jean-Bernard Pouvreau and François-Didier Boyer},

doi = {10.1016/j.phytochem.2019.112112},

issn = {1873-3700},

year  = {2019},

date = {2019-12-01},

urldate = {2019-12-01},

journal = {Phytochemistry},

volume = {168},

pages = {112112},

abstract = {Strigolactone (SL) plant hormones control plant architecture and are key players in both symbiotic and parasitic interactions. GR24, a synthetic SL analog, is the worldwide reference compound used in all bioassays for investigating the role of SLs in plant development and in rhizospheric interactions. In 2012, the first characterization of the SL receptor reported the detection of an unknown compound after incubation of GR24 samples with the SL receptor. We reveal here the origin of this compound (P270), which comes from a by-product formed during GR24 chemical synthesis. We present the identification of this by-product, named contalactone. A proposed chemical pathway for its formation is provided as well as an evaluation of its bioactivity on pea, Arabidopsis, root parasitic plant seeds and AM fungi, characterizing it as a SL mimic. Quality of GR24 samples can be easily checked by carrying out microscale hydrolysis in a basic aqueous medium to easily detect P270 as indicator of the presence of the contalactone impurity. In all cases, before being used for bioassays, GR24 must be careful purified by preparative HPLC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gheyouche2019,

title = {Docknmine, a web portal to assemble and analyse virtual and experimental interaction data},

author = {Ennys Gheyouche and Romain Launay and Jean Lethiec and Antoine Labeeuw and Caroline Roze and Alan Amossé and Stéphane Téletchéa},

doi = {10.3390/ijms20205062},

issn = {14220067},

year  = {2019},

date = {2019-10-01},

journal = {International Journal of Molecular Sciences},

volume = {20},

number = {20},

publisher = {MDPI AG},

abstract = {Scientists have to perform multiple experiments producing qualitative and quantitative data to determine if a compound is able to bind to a given target. Due to the large diversity of the potential ligand chemical space, the possibility of experimentally exploring a lot of compounds on a target rapidly becomes out of reach. Scientists therefore need to use virtual screening methods to determine the putative binding mode of ligands on a protein and then post-process the raw docking experiments with a dedicated scoring function in relation with experimental data. Two of the major difficulties for comparing docking predictions with experiments mostly come from the lack of transferability of experimental data and the lack of standardisation in molecule names. Although large portals like PubChem or ChEMBL are available for general purpose, there is no service allowing a formal expert annotation of both experimental data and docking studies. To address these issues, researchers build their own collection of data in flat files, often in spreadsheets, with limited possibilities of extensive annotations or standardisation of ligand descriptions allowing cross-database retrieval. We have conceived the dockNmine platform to provide a service allowing an expert and authenticated annotation of ligands and targets. First, this portal allows a scientist to incorporate controlled information in the database using reference identifiers for the protein (Uniprot ID) and the ligand (SMILES description), the data and the publication associated to it. Second, it allows the incorporation of docking experiments using forms that automatically parse useful parameters and results. Last, the web interface provides a lot of pre-computed outputs to assess the degree of correlations between docking experiments and experimental data.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tripathi2019,

title = {Investigation of phospholipase Cγ1 interaction with SLP76 using molecular modeling methods for identifying novel inhibitors},

author = {Neha Tripathi and Iyanar Vetrivel and Stéphane Téletchéa and Mickaël Jean and Patrick Legembre and Adèle D Laurent},

doi = {10.3390/ijms20194721},

issn = {14220067},

year  = {2019},

date = {2019-10-01},

journal = {International Journal of Molecular Sciences},

volume = {20},

number = {19},

publisher = {MDPI AG},

abstract = {The enzyme phospholipase C gamma 1 (PLCγ1) has been identified as a potential drug target of interest for various pathological conditions such as immune disorders, systemic lupus erythematosus, and cancers. Targeting its SH3 domain has been recognized as an efficient pharmacological approach for drug discovery against PLCγ1. Therefore, for the first time, a combination of various biophysical methods has been employed to shed light on the atomistic interactions between PLCγ1 and its known binding partners. Indeed, molecular modeling of PLCγ1 with SLP76 peptide and with previously reported inhibitors (ritonavir, anethole, daunorubicin, diflunisal, and rosiglitazone) facilitated the identification of the common critical residues (Gln805, Arg806, Asp808, Glu809, Asp825, Gly827, and Trp828) as well as the quantification of their interaction through binding energies calculations. These features are in agreement with previous experimental data. Such an in depth biophysical analysis of each complex provides an opportunity to identify new inhibitors through pharmacophore mapping, molecular docking and MD simulations. From such a systematic procedure, a total of seven compounds emerged as promising inhibitors, all characterized by a strong binding with PLCγ1 and a comparable or higher binding affinity to ritonavir (ΔGbind < -25 kcal/mol), one of the most potent inhibitor reported till now.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{AjjolliNagaraja2019,

title = {Flux prediction using artificial neural network (ANN) for the upper part of glycolysis},

author = {Anamya {Ajjolli Nagaraja} and Nicolas Fontaine and Mathieu Delsaut and Philippe Charton and Cedric Damour and Bernard Offmann and Brigitte Grondin-Perez and Frédéric Cadet},

editor = {Marie-Joelle Virolle},

url = {https://dx.plos.org/10.1371/journal.pone.0216178},

doi = {10.1371/journal.pone.0216178},

issn = {1932-6203},

year  = {2019},

date = {2019-05-01},

journal = {PLOS ONE},

volume = {14},

number = {5},

pages = {e0216178},

publisher = {Public Library of Science},

abstract = {The selection of optimal enzyme concentration in multienzyme cascade reactions for the highest product yield in practice is very expensive and time-consuming process. The modelling of biological pathways is a difficult process because of the complexity of the system. The mathematical modelling of the system using an analytical approach depends on the many parameters of enzymes which rely on tedious and expensive experiments. The artificial neural network (ANN) method has been successively applied in different fields of science to perform complex functions. In this study, ANN models were trained to predict the flux for the upper part of glycolysis as inferred by NADH consumption, using four enzyme concentrations i.e., phosphoglucoisomerase, phosphofructokinase, fructose-bisphosphate-aldolase, triose-phosphate-isomerase. Out of three ANN algorithms, the neuralnet package with two activation functions, “logistic” and “tanh” were implemented. The prediction of the flux was very efficient: RMSE and R2 were 0.847, 0.93 and 0.804, 0.94 respectively for logistic and tanh functions using a cross validation procedure. This study showed that a systemic approach such as ANN could be used for accurate prediction of the flux through the metabolic pathway. This could help to save a lot of time and costs, particularly from an industrial perspective. The R-code is available at: https://github.com/DSIMB/ANN-Glycolysis-Flux-Prediction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Teletchea2019,

title = {Repository of enriched structures of proteins involved in the red blood cell environment (RESPIRE)},

author = {Stéphane Téletchéa and H Santuz and S Léonard and Catherine Etchebest},

doi = {10.1371/journal.pone.0211043},

issn = {19326203},

year  = {2019},

date = {2019-02-01},

journal = {PLoS ONE},

volume = {14},

number = {2},

publisher = {Public Library of Science},

abstract = {The Red Blood Cell (RBC) is a metabolically-driven cell vital for processes such a gas transport and homeostasis. RBC possesses at its surface exposing antigens proteins that are critical in blood transfusion. Due to their importance, numerous studies address the cell function as a whole but more and more details of RBC structure and protein content are now studied using massive state-of-the art characterisation techniques. Yet, the resulting information is frequently scattered in many scientific articles, in many databases and specialized web servers. To provide a more compendious view of erythrocytes and of their protein content, we developed a dedicated database called RESPIRE that aims at gathering a comprehensive and coherent ensemble of information and data about proteins in RBC. This cell-driven database lists proteins found in erythrocytes. For a given protein entry, initial data are processed from external portals and enriched by using state-of-the-art bioinformatics methods. As structural information is extremely useful to understand protein function and predict the impact of mutations, a strong effort has been put on the prediction of protein structures with a special treatment for membrane proteins. Browsing the database is available through text search for reference gene names or protein identifiers, through pre-defined queries or via hyperlinks. The RESPIRE database provides valuable information and unique annotations that should be useful to a wide audience of biologists, clinicians and structural biologists.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Brissonnet2019a,

title = {Monitoring glycosidase activity for clustered sugar substrates, a study on β-glucuronidase},

author = {Yoan Brissonnet and Guillaume Compain and Brigitte Renoux and Eva Maria Krammer and Franck Daligault and David Deniaud and Sébastien Papot and Sébastien G Gouin},

doi = {10.1039/c9ra08847d},

issn = {20462069},

year  = {2019},

date = {2019-01-01},

journal = {RSC Advances},

volume = {9},

number = {69},

pages = {40263--40267},

abstract = {Determination of glycosidase hydrolysis kinetics for a monovalent sugar substrate is relatively straightforward and classically achieved by monitoring the fluorescence signal released from the sugar-conjugated probe after enzymatic hydrolysis. Naturally occuring sugar epitopes are, however, often clustered on biopolymers or at biological surfaces, and previous reports have shown that glycosidase hydrolytic rates can differ greatly with multivalent presentation of the sugar epitopes. New probes are needed to make it easier to interpret the importance of substrate clustering towards a specific enzyme activity. In this work, we developed multivalent glucuronide substrates attached to fluorescent amino-coumarines through self-immolative linkers to enable real time-monitoring of the hydrolysing activity of E.coli β-glucuronidases (GUS) towards clustered substrates. GUS are exoglycosidases of considerable therapeutic interest cleaving β-d-glucuronides and are found in the lysosomes, in the tumoral microenvironment, and are expressed by gut microbiota. GUS showed a much lower catalytic efficiency in hydrolysing clustered glucuronides due to a significantly lower enzymatic velocity and affinity for the substrates. GUS was 52-fold less efficient in hydrolysing GlcA substrates presented on an octameric silsequioxane (COSS) compared with a monovalent GlcA of similar chemical structure. Thus, kinetic and thermodynamic data of GUS hydrolysis towards multivalent glucuronides were easily obtained with these new types of enzymatically-triggered probes. More generally, adapting the substrate nature and valency of these new probes, should improve understanding of the impact of multivalency for a specific enzyme.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Brinkø2019,

title = {Combining Click Reactions for the One-Pot Synthesis of Modular Biomolecule Mimetics},

author = {Anne Brinkø and Christian Risinger and Annie Lambert and Ola Blixt and Cyrille Grandjean and Henrik H Jensen},

doi = {10.1021/acs.orglett.9b02811},

issn = {15237052},

year  = {2019},

date = {2019-01-01},

journal = {Organic Letters},

volume = {21},

number = {18},

pages = {7544--7548},

abstract = {Here, we report on the first combined one-pot use of the two so-called "click reactions": The thiol-ene coupling and the copper-catalyzed alkyne-azide cycloaddition. These reactions were employed in an alternating and one-pot fashion to combine appropriately functionalized monomeric carbohydrate building blocks to create mimics of trisaccharides and tetrasaccharides as single anomers, with only minimal purification necessary. The deprotected oligosaccharide mimics were found to bind both plant lectins and human galectin-3.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pillot2019,

title = {Site-Specific Conjugation for Fully Controlled Glycoconjugate Vaccine Preparation},

author = {Aline Pillot and Alain Defontaine and Amina Fateh and Annie Lambert and Maruthi Prasanna and Mathieu Fanuel and Muriel Pipelier and Noemi Csaba and Typhaine Violo and Emilie Camberlein and Cyrille Grandjean},

doi = {10.3389/fchem.2019.00726},

issn = {22962646},

year  = {2019},

date = {2019-01-01},

journal = {Frontiers in Chemistry},

volume = {7},

number = {November},

pages = {1--9},

abstract = {Glycoconjugate vaccines are formed by covalently link a carbohydrate antigen to a carrier protein whose role is to achieve a long lasting immune response directed against the carbohydrate antigen. The nature of the sugar antigen, its length, its ratio per carrier protein and the conjugation chemistry impact on both structure and the immune response of a glycoconjugate vaccine. In addition it has long been assumed that the sites at which the carbohydrate antigen is attached can also have an impact. These important issue can now be addressed owing to the development of novel chemoselective ligation reactions as well as techniques such as site-selective mutagenesis, glycoengineering, or extension of the genetic code. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. A synthetic tetrasaccharide representative of the serotype 14 capsular polysaccharide of Streptococcus pneumoniae has been linked using the thiol/maleimide coupling chemistry to four different Pneumococcal surface adhesin A (PsaA) mutants, each harboring a single cysteine mutation at a defined position. Humoral response of these 1 to 1 carbohydrate antigen/PsaA conjugates have been assessed in mice. Our results showed that the carbohydrate antigen-PsaA connectivity impacts the anti-carrier response and raise questions about the design of glycoconjugate vaccine whereby the protein plays the dual role of immunogen and carrier.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{PRASANNA201931,

title = {Semisynthetic glycoconjugate based on dual role protein/PsaA as a pneumococcal vaccine},

author = {Maruthi Prasanna and Daphnée Soulard and Emilie Camberlein and Nicolas Ruffier and Annie Lambert and François Trottein and Noemi Csaba and Cyrille Grandjean},

url = {http://www.sciencedirect.com/science/article/pii/S0928098718305487},

doi = {https://doi.org/10.1016/j.ejps.2018.12.013},

issn = {0928-0987},

year  = {2019},

date = {2019-01-01},

journal = {European Journal of Pharmaceutical Sciences},

volume = {129},

pages = {31--41},

abstract = {Pneumococcal infections remain a major public health concern worldwide. The currently available vaccines in the market are based on pneumococcal capsular polysaccharides but they still need to be improved to secure an optimal coverage notably in population at risk. To circumvent this, association of virulence pneumococcal proteins to the polysaccharide valencies has been proposed with the hope to observe an additive - if not synergistic - protective effect. Along this line, the use of the highly conserved and ubiquitous pneumococcal surface adhesin A (PsaA) as a protein carrier for a synthetic pneumococcal oligosaccharide is demonstrated herein for the first time. A tetrasaccharide mimicking functional antigenic determinants from the S. pneumoniae serotype 14 capsular polysaccharide (Pn14TS) was chemically synthesised. The mature PsaA (mPsaA) was expressed in E. coli and purified using affinity chromatography. The Pn14PS was conjugated to mPsaA using maleimide-thiol coupling chemistry to obtain mPsaA-Pn14PS conjugate (protein/sugar molar ratio: 1/5.4). The mPsaA retained the structural conformation after the conjugation and lyophilisation. The prepared glycoconjugate adjuvanted with α-galactosylceramide, a potent activator of invariant Natural Killer T cells, was tested in mice for its immunological response upon subcutaneous injection in comparison with mPsaA alone and a model BSA conjugate (BSA-Pn14PS, used here as a control). Mice immunised with the mPsaA-Pn14TS produced a robust IgG response against mPsaA and against the capsular polysaccharide from pneumococcal serotype 14. These data provide the basis for novel pneumococcal vaccine development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Brissonnet2019b,

title = {Multivalent Thiosialosides and Their Synergistic Interaction with Pathogenic Sialidases},

author = {Yoan Brissonnet and Coralie Assailly and Amélie Saumonneau and Julie Bouckaert and Mike Maillasson and Clémence Petitot and Benoit Roubinet and Blanka Didak and Ludovic Landemarre and Clarisse Bridot and Ralf Blossey and David Deniaud and Xibo Yan and Julien Bernard and Charles Tellier and Cyrille Grandjean and Franck Daligault and Sébastien G Gouin},

doi = {10.1002/chem.201805790},

issn = {15213765},

year  = {2019},

date = {2019-01-01},

journal = {Chemistry - A European Journal},

volume = {25},

number = {9},

pages = {2358--2365},

abstract = {Sialidases (SAs) hydrolyze sialyl residues from glycoconjugates of the eukaryotic cell surface and are virulence factors expressed by pathogenic bacteria, viruses, and parasites. The catalytic domains of SAs are often flanked with carbohydrate-binding module(s) previously shown to bind sialosides and to enhance enzymatic catalytic efficiency. Herein, non-hydrolyzable multivalent thiosialosides were designed as probes and inhibitors of V. cholerae, T. cruzi, and S. pneumoniae (NanA) sialidases. NanA was truncated from the catalytic and lectinic domains (NanA-L and NanA-C) to probe their respective roles upon interacting with sialylated surfaces and the synthetically designed di- and polymeric thiosialosides. The NanA-L domain was shown to fully drive NanA binding, improving affinity for the thiosialylated surface and compounds by more than two orders of magnitude. Importantly, each thiosialoside grafted onto the polymer was also shown to reduce NanA and NanA-C catalytic activity with efficiency that was 3000-fold higher than that of the monovalent thiosialoside reference. These results extend the concept of multivalency for designing potent bacterial and parasitic sialidase inhibitors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Naretto2019,

title = {The agar-specific hydrolase ZgAgaC from the marine bacterium Zobellia galactanivorans defines a new GH16 protein subfamily},

author = {Anaïs Naretto and Mathieu Fanuel and David Ropartz and Hélène Rogniaux and Robert Larocque and Mirjam Czjzek and Charles Tellier and Gurvan Michel},

doi = {10.1074/jbc.RA118.006609},

issn = {1083351X},

year  = {2019},

date = {2019-01-01},

journal = {Journal of Biological Chemistry},

volume = {294},

number = {17},

pages = {6923--6939},

abstract = {Agars are sulfated galactans from red macroalgae and are composed of a D-galactose (G unit) and L-galactose (L unit) alternatively linked by α-1, 3 and β-1, 4 glycosidicbonds. The sepolysaccharides display high complexity, with numerous modifications of their backbone (e.g. presence of a 3, 6-anhydro-bridge (LA unit) and sulfations and methylation). Currently, bacterial polysaccharidases that hydrolyze agars (α-agarases and α-porphyranases) have been characterized on simple agarose and more rarely on porphyran, a polymer containing both agarobiose (G-LA) and porphyranobiose (GL6S) motifs. How bacteria can degrade complex agars remains therefore an open question. Here, we studied an enzyme from the marine bacterium Zobellia galactanivorans (ZgAgaC) that is distantly related to the glycoside hydrolase 16 (GH16) family α-agarases and α-porphyranases. Using a large red algae collection, we demonstrate that ZgAgaC hydrolyzes not only agarose but also complex agars from Ceramiales species. Using tandem MS analysis, we elucidated the structure of a purified hexasaccharide product, L6S-G-LA2Me-G(2Pentose)-LA2S-G, released by the activity of ZgAgaC on agar extracted from Osmundea pinnatifida. By resolving the crystal structure of ZgAgaC at high resolution (1.3 Å) and comparison with the structures of ZgAgaB and ZgPorA in complex with their respective substrates, we determined that ZgAgaC recognizes agarose via a mechanism different from that of classical α-agarases. Moreover, we identified conserved residues involved in the binding of complex oligoagars and demonstrate a probable influence of the acidic polysaccharide's pH microenvironment on hydrolase activity. Finally, a phylogenetic analysis supported the notion that ZgAgaC homologs define a new GH16 subfamily distinct from α-porphyranases and classical α-agarases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1093/protein/gzz032,

title = {Toward the design of efficient transglycosidases: the case of the GH1 of Thermus thermophilus},

author = {Benoit David and Philippe Arnaud and Charles Tellier and Yves-Henri Sanejouand},

url = {https://doi.org/10.1093/protein/gzz032},

doi = {10.1093/protein/gzz032},

issn = {1741-0126},

year  = {2019},

date = {2019-01-01},

journal = {Protein Engineering, Design and Selection},

volume = {32},

number = {7},

pages = {309--316},

abstract = {Using the information available in the sequences of well-characterized transglycosidases found in plants, mutations were introduced in the glycoside hydrolase of the bacterium Thermus thermophilus, with the aim of turning it into an efficient transglycosidase. All mutants happen to have fair catalytic efficiencies, being at worst 25 times less efficient than the wild type. Noteworthy, W120F, one of our high transglycosylation yield (≈ 50%) mutants, is only two times less efficient than the wild type. Interestingly, while in the wild type the sidechain of the acid–base is only found able to sample a pair of equivalent conformations during 0.5-µs-long molecular dynamics simulations, its flexibility is much higher in the case of the high transglycosylation yield mutants. Our results thus suggest that engineering the flexibility of the acid–base of a retaining glycoside hydrolase could be a general way to turn it into an efficient transglycosidase.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{VELIC2019187,

title = {Interactions of the Rad51 inhibitor DIDS with human and bovine serum albumins: Optical spectroscopy and isothermal calorimetry approaches},

author = {Denis Velic and Cathy Charlier and Milena Popova and Titouan Jaunet-Lahary and Zakaria Bouchouireb and Sébastien Henry and Pierre Weigel and Jean-Yves Masson and Adèle D Laurent and Igor Nabiev and Fabrice Fleury},

url = {http://www.sciencedirect.com/science/article/pii/S0300908419302743},

doi = {https://doi.org/10.1016/j.biochi.2019.09.016},

issn = {0300-9084},

year  = {2019},

date = {2019-01-01},

journal = {Biochimie},

volume = {167},

pages = {187--197},

abstract = {Rad51 is a key protein in DNA repair by homologous recombination and an important target for development of drugs in cancer therapy. 4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) has been used in clinic during the past 30 years as an inhibitor of anion transporters and channels. Recently DIDS has been demonstrated to affect Rad51-mediated homologous pairing and strand exchange, key processes in homologous recombination. Consequently, DIDS has been considered as a potential revertant of radio- and chemo-resistance of cancer cells, the major causes of therapy failure. Here, we have investigated the behavior of DIDS towards serum albumins. The effects of environmental factors, primarily, solvent polarity, on DIDS stability were evaluated, and the mechanisms of interaction of DIDS with human or bovine serum albumin were analyzed using isothermal calorimetry, circular dichroism and fluorescence spectroscopies. DIDS interaction with both serum albumins have been demonstrated, and the interaction characteristics have been determined. By comparing these characteristics for several DIDS derivatives, we have identified the DIDS moiety essential for the interaction. Furthermore, site competition data indicate that human albumin has two DIDS-binding sites: a high-affinity site in the IIIA subdomain and a low-affinity one in the IB subdomain. Molecular docking has revealed the key molecular moieties of DIDS responsible for its interactions in each site and shown that the IB site can bind two ligands. These findings show that binding of DIDS to serum albumin may change the balance between the free and bound DIDS forms, thereby affecting its bioavailability and efficacy against Rad51.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chabot2019a,

title = {New phosphorylation sites of rad51 by c-met modulates presynaptic filament stability},

author = {Thomas Chabot and Alain Defontaine and Damien Marquis and Axelle Renodon-Corniere and Emmanuelle Courtois and Fabrice Fleury and Yvonnick Cheraud},

doi = {10.3390/cancers11030413},

issn = {20726694},

year  = {2019},

date = {2019-01-01},

journal = {Cancers},

volume = {11},

number = {3},

abstract = {Genomic instability through deregulation of DNA repair pathways can initiate cancer and subsequently result in resistance to chemo and radiotherapy. Understanding these biological mechanisms is therefore essential to overcome cancer. RAD51 is the central protein of the Homologous Recombination (HR) DNA repair pathway, which leads to faithful DNA repair of DSBs. The recombinase activity of RAD51 requires nucleofilament formation and is regulated by post-translational modifications such as phosphorylation. In the last decade, studies have suggested the existence of a relationship between receptor tyrosine kinases (RTK) and Homologous Recombination DNA repair. Among these RTK the c-MET receptor is often overexpressed or constitutively activated in many cancer types and its inhibition induces the decrease of HR. In this study, we show for the first time that c-MET is able to phosphorylate the RAD51 protein. We demonstrate in vitro that c-MET phosphorylates four tyrosine residues localized mainly in the subunit-subunit interface of RAD51. Whereas these post-translational modifications do not affect the presynaptic filament formation, they strengthen its stability against the inhibitor effect of the BRC peptide obtained from BRCA2. Taken together, these results confirm the role of these modifications in the regulation of the BRCA2-RAD51 interaction and underline the importance of c-MET in DNA damage response.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN7,

title = {CYP707As are effectors of karrikin and strigolactone signalling pathways in Arabidopsis thaliana and parasitic plants},

author = {Guillaume Brun and Séverine Thoiron and Lukas Braem and Jean-Bernard Pouvreau and Grégory Montiel and Marc-Marie Lechat and Philippe Simier and Kris Gevaert and Sophie Goormachtig and Philippe Delavault},

url = {https://onlinelibrary.wiley.com/doi/10.1111/pce.13594},

doi = {10.1111/pce.13594},

issn = {0140-7791},

year  = {2019},

date = {2019-01-01},

urldate = {2019-01-01},

journal = {Plant Cell Environ},

volume = {42},

number = {9},

pages = {2612-2626},

abstract = {Karrikins stimulate Arabidopsis thaliana germination, whereas parasitic weeds of the Orobanchaceae family have evolved to respond to host-exuded compounds such as strigolactones, dehydrocostus lactone, and 2-phenylethyl isothiocyanate. In Phelipanche ramosa, strigolactone-induced germination was shown to require one of the CYP707A proteins involved in abscisic acid catabolism. Here, germination and gene expression were analysed to investigate the role of CYP707As in germination of both parasitic plants and Arabidopsis upon perception of germination stimulants, after using pharmacological inhibitors and Arabidopsis mutants disrupting germination signals. CYP707A genes were up-regulated upon treatment with effective germination stimulants in both parasitic plants and Arabidopsis. Obligate parasitic plants exhibited both intensified up-regulation of CYP707A genes and increased sensitivity to the CYP707A inhibitor abscinazole-E2B, whereas Arabidopsis cyp707a mutants still positively responded to germination stimulation. In Arabidopsis, CYP707A regulation required the canonical karrikin signalling pathway KAI2/MAX2/SMAX1 and the transcription factor WRKY33. Finally, CYP707As and WRKY33 also modulated Arabidopsis root architecture in response to the synthetic strigolactone rac-GR24, and wrky33-1 exhibited a shoot hyperbranched phenotype. This study suggests that the lack of host-independent germination in obligate parasites is associated with an exacerbated CYP707A induction and that CYP707As and WRKY33 are new players involved in a variety of strigolactone/karrikin responses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN32,

title = {Genetic differentiation and host preference reveal non-exclusive host races in the generalist parasitic weed Phelipanche ramosa},

author = {Bojana Stojanova and Régine Delourme and Philippe Duffé and Philippe Delavault and Philippe Simier},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/wre.12353 

https://onlinelibrary.wiley.com/doi/10.1111/wre.12353},

doi = {https://doi.org/10.1111/wre.12353},

issn = {0043-1737},

year  = {2019},

date = {2019-01-01},

urldate = {2019-01-01},

journal = {Weed Research},

volume = {59},

number = {2},

pages = {107-118},

abstract = {Summary We developed 20 microsatellite markers to genotype over 100 populations of the parasitic weed Phelipanche ramosa, which covers a wide host crop and geographic range. A representative core collection of 15 populations was also used in cross-infestation assays to study host preference during germination, attachment and shoot formation. We observed low genetic differentiation within most of the populations, but high genetic differentiation between populations partitioned into 3 genetic groups with different host preferences and geographic distributions. Genetic group 1 is detected exclusively in western France and on various host crops, notably winter oilseed rape (WOSR) and not hemp. Cross-infection assays confirmed its incompatibility with hemp and showed its preference for WOSR and tobacco in terms of germination and attachment success. The group 2 populations share a large geographic distribution in France and Europe, low germination success with WOSR and high germination success, attachment success and shoot formation with hemp, tobacco or tomato. The subclades 2a and 2b include most of the French populations in hemp crops in eastern France and in tobacco fields in several European countries respectively. The genetic analyses revealed the potential of the three groups to increase their geographic range in the future. Intermediate genetic groups showed higher intrapopulation diversity and represent potential stocks for new host race emergence. Those findings argue in favour of the existence of host races in P. ramosa and should be considered for appropriate management strategies, notably in breeding programmes for resistance against this parasitic weed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Murik2019,

title = {Downregulation of mitochondrial alternative oxidase affects chloroplast function, redox status and stress response in a marine diatom},

author = {Omer Murik and Leila Tirichine and Judit Prihoda and Yann Thomas and Wagner L Ara{ú}jo and Andrew E Allen and Alisdair R Fernie and Chris Bowler},

doi = {10.1111/nph.15479},

issn = {14698137},

year  = {2019},

date = {2019-01-01},

journal = {New Phytologist},

volume = {221},

number = {3},

pages = {1303--1316},

abstract = {Diatom dominance in contemporary aquatic environments indicates that they have developed unique and effective mechanisms to cope with the rapid and considerable fluctuations that characterize these environments. In view of their evolutionary history from a secondary endosymbiosis, inter-organellar regulation of biochemical activities may be of particular relevance. Diatom mitochondrial alternative oxidase (AOX) is believed to play a significant role in supplying chloroplasts with ATP produced in the mitochondria. Using the model diatom Phaeodactylum tricornutum we generated AOX knockdown lines, and followed sensitivity to stressors, photosynthesis and transcriptome and metabolome profiles of wild-type and knockdown lines. We show here that expression of the AOX gene is upregulated by various stresses including H 2 O 2 , heat, high light illumination, and iron or nitrogen limitation. AOX knockdown results in hypersensitivity to stress. Knockdown lines also show significantly reduced photosynthetic rates and their chloroplasts are more oxidized. Comparisons of transcriptome and metabolome profiles suggest a strong impact of AOX activity on gene expression, which is carried through to the level of the metabolome. Our data provide evidence for the involvement of mitochondrial AOX in processes central to the cell biology of diatoms, revealing that cross-talk between mitochondria and chloroplasts is crucial for maintaining sensitivity to changing environments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}