@article{chabrolles_hepatitis_2020,

title = {Hepatitis B virus Core protein nuclear interactome identifies SRSF10 as a host RNA-binding protein restricting HBV RNA production},

author = {Hélène Chabrolles and Héloïse Auclair and Serena Vegna and Thomas Lahlali and Caroline Pons and Maud Michelet and Yohann Couté and Lucid Belmudes and Gilliane Chadeuf and Yujin Kim and Ariel Di Bernardo and Pascal Jalaguier and François-Loïc Cosset and Floriane Fusil and Michel Rivoire and Lee D Arnold and Uri Lopatin and Christophe Combet and Fabien Zoulim and David Grierson and Benoit Chabot and Julie Lucifora and David Durantel and Anna Salvetti},

doi = {10.1371/journal.ppat.1008593},

issn = {1553-7374},

year  = {2020},

date = {2020-01-01},

journal = {PLoS pathogens},

volume = {16},

number = {11},

pages = {e1008593},

abstract = {Despite the existence of a preventive vaccine, chronic infection with Hepatitis B virus (HBV) affects more than 250 million people and represents a major global cause of hepatocellular carcinoma (HCC) worldwide. Current clinical treatments, in most of cases, do not eliminate viral genome that persists as a DNA episome in the nucleus of hepatocytes and constitutes a stable template for the continuous expression of viral genes. Several studies suggest that, among viral factors, the HBV core protein (HBc), well-known for its structural role in the cytoplasm, could have critical regulatory functions in the nucleus of infected hepatocytes. To elucidate these functions, we performed a proteomic analysis of HBc-interacting host-factors in the nucleus of differentiated HepaRG, a surrogate model of human hepatocytes. The HBc interactome was found to consist primarily of RNA-binding proteins (RBPs), which are involved in various aspects of mRNA metabolism. Among them, we focused our studies on SRSF10, a RBP that was previously shown to regulate alternative splicing (AS) in a phosphorylation-dependent manner and to control stress and DNA damage responses, as well as viral replication. Functional studies combining SRSF10 knockdown and a pharmacological inhibitor of SRSF10 phosphorylation (1C8) showed that SRSF10 behaves as a restriction factor that regulates HBV RNAs levels and that its dephosphorylated form is likely responsible for the anti-viral effect. Surprisingly, neither SRSF10 knock-down nor 1C8 treatment modified the splicing of HBV RNAs but rather modulated the level of nascent HBV RNA. Altogether, our work suggests that in the nucleus of infected cells HBc interacts with multiple RBPs that regulate viral RNA metabolism. Our identification of SRSF10 as a new anti-HBV restriction factor offers new perspectives for the development of new host-targeted antiviral strategies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{van_lis_hybrid_2020,

title = {Hybrid cluster proteins in a photosynthetic microalga},

author = {Robert Lis and Sabine Brugière and Carole Baffert and Yohann Couté and Wolfgang Nitschke and Ariane Atteia},

doi = {10.1111/febs.15025},

issn = {1742-4658},

year  = {2020},

date = {2020-01-01},

journal = {The FEBS journal},

volume = {287},

number = {4},

pages = {721--735},

abstract = {Hybrid cluster proteins (HCPs) are metalloproteins characterized by the presence of an iron-sulfur-oxygen cluster. These proteins occur in all three domains of life. In eukaryotes, HCPs have so far been found only in a few anaerobic parasites and photosynthetic microalgae. With respect to all species harboring an HCP, the green microalga Chlamydomonas reinhardtii stands out by the presence of four HCP genes. The study of the gene and protein structures as well as the phylogenetic analyses strongly support a model in which the HCP family in the alga has emerged from a single gene of alpha proteobacterial origin and then expanded by several rounds of duplications. The spectra and redox properties of HCP1 and HCP3, produced heterologously in Escherichia coli, were analyzed by electron paramagnetic resonance spectroscopy on redox-titrated samples. Both proteins contain a [4Fe-4S]-cluster as well as a [4Fe-2O-2S]-hybrid cluster with paramagnetic properties related to those of HCPs from Desulfovibrio species. Immunoblotting experiments combined with mass spectrometry-based proteomics showed that both nitrate and darkness contribute to the strong upregulation of the HCP levels in C. reinhardtii growing under oxic conditions. The link to the nitrate metabolism is discussed in the light of recent data on the potential role of HCP in S-nitrosylation in bacteria.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{adrait_liquid_2020,

title = {Liquid Biopsy of Bile based on Targeted Mass Spectrometry for the Diagnosis of Malignant Biliary Strictures},

author = {Annie Adrait and Jean-Marc Dumonceau and Myriam Delhaye and Isabelle Annessi-Ramseyer and Jean-Louis Frossard and Yohann Coute and Annarita Farina},

doi = {10.1111/cts.12890},

issn = {1752-8062},

year  = {2020},

date = {2020-01-01},

journal = {Clinical and Translational Science},

abstract = {Bile holds biomarkers of malignant biliary strictures (MBS) but is unsuited for automated analyzers used in routine diagnostic laboratories. Selected Reaction Monitoring (SRM) is a flexible high-throughput analytical approach based on targeted mass spectrometry (MS) already implemented in clinical settings. We tested the hypothesis that SRM could be used to quantify cancer biomarkers in human bile. An SRM-based assay was developed to simultaneously quantify up to 37 peptides from 13 bile proteins in a developmental cohort of 15 patients (MBS},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{coute_mass_2020,

title = {Mass Spectrometry-Based Characterization of the Virion Proteome, Phosphoproteome, and Associated Kinase Activity of Human Cytomegalovirus},

author = {Yohann Couté and Alexandra Kraut and Christine Zimmermann and Nicole Büscher and Anne-Marie Hesse and Christophe Bruley and Marco De Andrea and Christina Wangen and Friedrich Hahn and Manfred Marschall and Bodo Plachter},

url = {https://www.mdpi.com/2076-2607/8/6/820},

doi = {10.3390/microorganisms8060820},

issn = {2076-2607},

year  = {2020},

date = {2020-01-01},

journal = {Microorganisms},

volume = {8},

number = {6},

pages = {820},

abstract = {The assembly of human cytomegalovirus (HCMV) virions is an orchestrated process that requires, as an essential prerequisite, the complex crosstalk between viral structural proteins. Currently, however, the mechanisms governing the successive steps in the constitution of virion protein complexes remain elusive. Protein phosphorylation is a key regulator determining the sequential changes in the conformation, binding, dynamics, and stability of proteins in the course of multiprotein assembly. In this review, we present a comprehensive map of the HCMV virion proteome, including a refined view on the virion phosphoproteome, based on previous publications supplemented by new results. Thus, a novel dataset of viral and cellular proteins contained in HCMV virions is generated, providing a basis for future analyses of individual phosphorylation steps and sites involved in the orchestrated assembly of HCMV virion-specific multiprotein complexes. Finally, we present the current knowledge on the activity of pUL97, the HCMV-encoded and virion-associated kinase, in phosphorylating viral and host proteins.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{crespo_multi-omic_2020,

title = {Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes},

author = {Marion Crespo and Annelaure Damont and Melina Blanco and Emmanuelle Lastrucci and Sara El Kennani and Côme Ialy-Radio and Laila El Khattabi and Samuel Terrier and Mathilde Louwagie and Sylvie Kieffer-Jaquinod and Anne-Marie Hesse and Christophe Bruley and Sophie Chantalat and Jérôme Govin and François Fenaille and Christophe Battail and Julie Cocquet and Delphine Pflieger},

url = {https://academic.oup.com/nar/article/48/8/4115/5809165},

doi = {10.1093/nar/gkaa163},

issn = {0305-1048, 1362-4962},

year  = {2020},

date = {2020-01-01},

journal = {Nucleic Acids Research},

volume = {48},

number = {8},

pages = {4115--4138},

abstract = {Abstract 

Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{kloehn_multi-omics_2020,

title = {Multi-omics analysis delineates the distinct functions of sub-cellular acetyl-CoA pools in Toxoplasma gondii},

author = {Joachim Kloehn and Rebecca D Oppenheim and Ghizal Siddiqui and Pieter-Jan De Bock and Sunil Kumar Dogga and Yohann Coute and Mohamed-Ali Hakimi and Darren J Creek and Dominique Soldati-Favre},

url = {https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-020-00791-7},

doi = {10.1186/s12915-020-00791-7},

issn = {1741-7007},

year  = {2020},

date = {2020-01-01},

journal = {BMC Biology},

volume = {18},

number = {1},

pages = {67},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sansa_optomechanical_2020,

title = {Optomechanical mass spectrometry},

author = {Marc Sansa and Martial Defoort and Ariel Brenac and Maxime Hermouet and Louise Banniard and Alexandre Fafin and Marc Gely and Christophe Masselon and Ivan Favero and Guillaume Jourdan and Sébastien Hentz},

doi = {10.1038/s41467-020-17592-9},

issn = {2041-1723},

year  = {2020},

date = {2020-01-01},

journal = {Nature Communications},

volume = {11},

number = {1},

pages = {3781},

abstract = {Nanomechanical mass spectrometry has proven to be well suited for the analysis of high mass species such as viruses. Still, the use of one-dimensional devices such as vibrating beams forces a trade-off between analysis time and mass resolution. Complex readout schemes are also required to simultaneously monitor multiple resonance modes, which degrades resolution. These issues restrict nanomechanical MS to specific species. We demonstrate here single-particle mass spectrometry with nano-optomechanical resonators fabricated with a Very Large Scale Integration process. The unique motion sensitivity of optomechanics allows designs that are impervious to particle position, stiffness or shape, opening the way to the analysis of large aspect ratio biological objects of great significance such as viruses with a tail or fibrils. Compared to top-down beam resonators with electrical read-out and state-of-the-art mass resolution, we show a three-fold improvement in capture area with no resolution degradation, despite the use of a single resonance mode.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Postic2020,

title = {Probing Protein Interaction Networks by Combining MS-Based Proteomics and Structural Data Integration.},

author = {Guillaume Postic and Julien Marcoux and Victor Reys and Jessica Andreani and Yves Vandenbrouck and Marie-Pierre Bousquet and Emmanuelle Mouton-Barbosa and Sarah Cianférani and Odile Burlet-Schiltz and Raphael Guerois and Gilles Labesse and Pierre Tufféry},

year  = {2020},

date = {2020-01-01},

journal = {Journal of proteome research},

volume = {19},

number = {7},

pages = {2807--2820},

address = {United States},

abstract = {Protein-protein interactions play a major role in the molecular machinery of life, and various techniques such as AP-MS are dedicated to their identification. However, those techniques return lists of proteins devoid of organizational structure, not detailing which proteins interact with which others. Proposing a hierarchical view of the interactions between the members of the flat list becomes highly tedious for large data sets when done by hand. To help hierarchize this data, we introduce a new bioinformatics protocol that integrates information of the multimeric protein 3D structures available in the Protein Data Bank using remote homology detection, as well as information related to Short Linear Motifs and interaction data from the BioGRID. We illustrate on two unrelated use-cases of different complexity how our approach can be useful to decipher the network of interactions hidden in the list of input proteins, and how it provides added value compared to state-of-the-art resources such as Interactome3D or STRING. Particularly, we show the added value of using homology detection to distinguish between orthologs and paralogs, and to distinguish between core obligate and more facultative interactions. We also demonstrate the potential of considering interactions occurring through Short Linear Motifs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{dia_reduced_2020,

title = {Reduced reticulum–mitochondria Ca2+ transfer is an early and reversible trigger of mitochondrial dysfunctions in diabetic cardiomyopathy},

author = {Maya Dia and Ludovic Gomez and Helene Thibault and Nolwenn Tessier and Christelle Leon and Christophe Chouabe and Sylvie Ducreux and Noelle Gallo-Bona and Emily Tubbs and Nadia Bendridi and Stephanie Chanon and Aymeric Leray and Lucid Belmudes and Yohann Couté and Mazen Kurdi and Michel Ovize and Jennifer Rieusset and Melanie Paillard},

url = {http://link.springer.com/10.1007/s00395-020-00835-7},

doi = {10.1007/s00395-020-00835-7},

issn = {0300-8428, 1435-1803},

year  = {2020},

date = {2020-01-01},

journal = {Basic Research in Cardiology},

volume = {115},

number = {6},

pages = {74},

abstract = {Abstract 

 

Type 2 diabetic cardiomyopathy features Ca 

2+ 

signaling abnormalities, notably an altered mitochondrial Ca 

2+ 

handling. We here aimed to study if it might be due to a dysregulation of either the whole Ca 

2+ 

homeostasis, the reticulum–mitochondrial Ca 

2+ 

coupling, and/or the mitochondrial Ca 

2+ 

entry through the uniporter. Following a 16-week high-fat high-sucrose diet (HFHSD), mice developed cardiac insulin resistance, fibrosis, hypertrophy, lipid accumulation, and diastolic dysfunction when compared to standard diet. Ultrastructural and proteomic analyses of cardiac reticulum–mitochondria interface revealed tighter interactions not compatible with Ca 

2+ 

transport in HFHSD cardiomyocytes. Intramyocardial adenoviral injections of Ca 

2+ 

sensors were performed to measure Ca 

2+ 

fluxes in freshly isolated adult cardiomyocytes and to analyze the direct effects of in vivo type 2 diabetes on cardiomyocyte function. HFHSD resulted in a decreased IP3R–VDAC interaction and a reduced IP3-stimulated Ca 

2+ 

transfer to mitochondria, with no changes in reticular Ca 

2+ 

level, cytosolic Ca 

2+ 

transients, and mitochondrial Ca 

2+ 

uniporter function. Disruption of organelle Ca 

2+ 

exchange was associated with decreased mitochondrial bioenergetics and reduced cell contraction, which was rescued by an adenovirus-mediated expression of a reticulum-mitochondria linker. An 8-week diet reversal was able to restore cardiac insulin signaling, Ca 

2+ 

transfer, and cardiac function in HFHSD mice. Therefore, our study demonstrates that the reticulum–mitochondria Ca 

2+ 

miscoupling may play an early and reversible role in the development of diabetic cardiomyopathy by disrupting primarily the mitochondrial bioenergetics. A diet reversal, by counteracting the MAM-induced mitochondrial Ca 

2+ 

dysfunction, might contribute to restore normal cardiac function and prevent the exacerbation of diabetic cardiomyopathy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{began_rhomboid_2020,

title = {Rhomboid intramembrane protease YqgP licenses bacterial membrane protein quality control as adaptor of FtsH textlessspan style=},

author = {Jakub Began and Baptiste Cordier and Jana Březinová and Jordan Delisle and Rozálie Hexnerová and Pavel Srb and Petra Rampírová and Milan Kožíšek and Mathieu Baudet and Yohann Couté and Anne Galinier and Václav Veverka and Thierry Doan and Kvido Strisovsky},

url = {https://onlinelibrary.wiley.com/doi/abs/10.15252/embj.2019102935},

doi = {10.15252/embj.2019102935},

issn = {0261-4189, 1460-2075},

year  = {2020},

date = {2020-01-01},

journal = {The EMBO Journal},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lezzerini_ribosomal_2020,

title = {Ribosomal protein gene RPL9 variants can differentially impair ribosome function and cellular metabolism},

author = {Marco Lezzerini and Marianna Penzo and Marie-Françoise O'Donohue and Carolina Marques Dos Santos Vieira and Manon Saby and Hyung L Elfrink and Illja J Diets and Anne-Marie Hesse and Yohann Couté and Marc Gastou and Alexandra Nin-Velez and Peter G J Nikkels and Alexandra N Olson and Evelien Zonneveld-Huijssoon and Marjolijn C J Jongmans and GuangJun Zhang and Michel Weeghel and Riekelt H Houtkooper and Marcin W Wlodarski and Roland P Kuiper and Marc B Bierings and Jutte Werff Ten Bosch and Thierry Leblanc and Lorenzo Montanaro and Jonathan D Dinman and Lydie Da Costa and Pierre-Emmanuel Gleizes and Alyson W MacInnes},

doi = {10.1093/nar/gkz1042},

issn = {1362-4962},

year  = {2020},

date = {2020-01-01},

journal = {Nucleic Acids Research},

volume = {48},

number = {2},

pages = {770--787},

abstract = {Variants in ribosomal protein (RP) genes drive Diamond-Blackfan anemia (DBA), a bone marrow failure syndrome that can also predispose individuals to cancer. Inherited and sporadic RP gene variants are also linked to a variety of phenotypes, including malignancy, in individuals with no anemia. Here we report an individual diagnosed with DBA carrying a variant in the 5'UTR of RPL9 (uL6). Additionally, we report two individuals from a family with multiple cancer incidences carrying a RPL9 missense variant. Analysis of cells from these individuals reveals that despite the variants both driving pre-rRNA processing defects and 80S monosome reduction, the downstream effects are remarkably different. Cells carrying the 5'UTR variant stabilize TP53 and impair the growth and differentiation of erythroid cells. In contrast, ribosomes incorporating the missense variant erroneously read through UAG and UGA stop codons of mRNAs. Metabolic profiles of cells carrying the 5'UTR variant reveal an increased metabolism of amino acids and a switch from glycolysis to gluconeogenesis while those of cells carrying the missense variant reveal a depletion of nucleotide pools. These findings indicate that variants in the same RP gene can drive similar ribosome biogenesis defects yet still have markedly different downstream consequences and clinical impacts.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{crespo_systematic_2020,

title = {Systematic genetic and proteomic screens during gametogenesis identify H2BK34 methylation as an evolutionary conserved meiotic mark},

author = {Marion Crespo and Lacey J Luense and Marie Arlotto and Hu Jialei and Jean Dorsey and Encar Garcia-Oliver and Parisha P Shah and Delphine Pflieger and Shelley L Berger and Jérôme Govin},

url = {https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-020-00349-5#citeas},

doi = {10.1186/s13072-020-00349-5},

year  = {2020},

date = {2020-01-01},

journal = {Epigenetics & Chromatin},

volume = {13},

number = {35},

pages = {1--23},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{hahn_target_2020,

title = {Target verification of artesunate-related antiviral drugs: assessing the role of mitochondrial and regulatory proteins by click chemistry and fluorescence labeling},

author = {Friedrich Hahn and Aischa Niesar and Christina Wangen and Markus Wild and Benedikt Grau and Lars Herrmann and Aysun Capci and Annie Adrait and Yohann Couté and Svetlana B Tsogoeva and Manfred Marschall},

url = {https://linkinghub.elsevier.com/retrieve/pii/S0166354220302758},

doi = {10.1016/j.antiviral.2020.104861},

issn = {01663542},

year  = {2020},

date = {2020-01-01},

journal = {Antiviral Research},

pages = {104861},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{vandenbrouck_functionally_2020,

title = {The Functionally Unannotated Proteome of Human Male Tissues: A Shared Resource to Uncover New Protein Functions Associated with Reproductive Biology},

author = {Yves Vandenbrouck and Charles Pineau and Lydie Lane},

doi = {10.1021/acs.jproteome.0c00516},

issn = {1535-3907},

year  = {2020},

date = {2020-01-01},

journal = {Journal of Proteome Research},

abstract = {In the context of the Human Proteome Project, we built an inventory of 412 functionally unannotated human proteins for which experimental evidence at the protein level exists (uPE1) and which are highly expressed in tissues involved in human male reproduction. We implemented a strategy combining literature mining, bioinformatics tools to collate annotation and experimental information from specific molecular public resources, and efficient visualization tools to put these unknown proteins into their biological context (protein complexes, tissue and subcellular location, expression pattern). The gathered knowledge allowed pinpointing five uPE1 for which a function has recently been proposed and which should be updated in protein knowledge bases. Furthermore, this bioinformatics strategy allowed to build new functional hypotheses for five other uPE1s in link with phenotypic traits that are specific to male reproductive function such as ciliogenesis/flagellum formation in germ cells (CCDC112 and TEX9), chromatin remodeling (C3orf62) and spermatozoon maturation (CCDC183). We also discussed the enigmatic case of MAGEB proteins, a poorly documented cancer/testis antigen subtype. Tools used and computational outputs produced during this study are freely accessible via ProteoRE (http://www.proteore.org), a Galaxy-based instance, for reuse purposes. We propose these five uPE1s should be investigated in priority by expert laboratories and hope that this inventory and shared resources will stimulate the interest of the community of reproductive biology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ngo_popn_2020,

title = {The PopN gate-keeper complex acts on the ATPase PscN to regulate the T3SS secretion switch from early to middle substrates in Pseudomonas aeruginosa},

author = {Tuan-Dung Ngo and Caroline Perdu and Bakhos Jneid and Michel Ragno and Julia Novion Ducassou and Alexandra Kraut and Yohann Couté and Charles Stopford and Ina Attree and Arne Rietsch and Eric Faudry},

url = {http://www.sciencedirect.com/science/article/pii/S0022283620306008},

doi = {10.1016/j.jmb.2020.10.024},

issn = {0022-2836},

year  = {2020},

date = {2020-01-01},

journal = {Journal of Molecular Biology},

abstract = {Pseudomonas aeruginosa is an opportunistic bacterium of which the main virulence factor is the Type III Secretion System. The ATPase of this machinery, PscN (SctN), is thought to be localized at the base of the secretion apparatus and to participate in the recognition, chaperone dissociation and unfolding of exported T3SS proteins. In this work, a protein-protein interaction ELISA revealed the interaction of PscN with a wide range of exported T3SS proteins including the needle, translocator, gate-keeper and effector. These interactions were further confirmed by Microscale Thermophoresis that also indicated a preferential interaction of PscN with secreted proteins or protein-chaperone complex rather than with chaperones alone, in line with the release of the chaperones in the bacterial cytoplasm after the dissociation from their exported proteins. Moreover, we suggest a new role of the gate-keeper complex and the ATPase in the regulation of early substrates recognition by the T3SS. This finding sheds a new light on the mechanism of secretion switching from early to middle substrates in P. aeruginosa.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lamboux_blood_2020,

title = {The blood copper isotopic composition is a prognostic indicator of the hepatic injury in Wilson disease},

author = {Aline Lamboux and Eduardo Couchonnal-Bedoya and Olivier Guillaud and Chloé Laurencin and Laurence Lion-François and Abdelouahed Belmalih and Elisabeth Mintz and Virginie Brun and Muriel Bost and Alain Lachaux and Vincent Balter},

doi = {10.1039/d0mt00167h},

issn = {1756-591X},

year  = {2020},

date = {2020-01-01},

journal = {Metallomics: Integrated Biometal Science},

abstract = {Wilson disease (WD) is an autosomal recessive disorder of copper (Cu) metabolism. The gene responsible for WD, ATP7B, is involved in the cellular transport of Cu, and mutations in the ATP7B gene induce accumulation of Cu in the liver and ultimately in the brain. In a pilot study, the natural variations of copper stable isotope ratios (65Cu/63Cu) in the serum of WD patients have been shown to differ from that of healthy controls. In the present study, we challenged these first results by measuring the 65Cu/63Cu ratios in the blood of treated (n = 25), naïve patients (n = 11) and age matched healthy controls (n = 75). The results show that naïve patients and healthy controls exhibit undistinguishable 65Cu/63Cu ratios, implying that the Cu isotopic ratio cannot serve as a reliable diagnostic biomarker. The type of treatment (d-penicillamine vs. triethylenetetramine) does not affect the 65Cu/63Cu ratios in WD patients, which remain constant regardless of the type and duration of the treatment. In addition, the 65Cu/63Cu ratios do not vary in naïve patients after the onset of the treatment. However, the 65Cu/63Cu ratios decrease with the degree of liver fibrosis and the gradient of the phenotypic presentation, i.e. presymptomatic, hepatic and neurologic. To get insights into the mechanisms at work, we study the effects of the progress of the WD on the organism by measuring the Cu concentrations and the 65Cu/63Cu ratios in the liver, feces and plasma of 12 and 45 week old Atp7b-/- mice. The evolution of the 65Cu/63Cu ratios is marked by a decrease in all tissues. The results show that 63Cu accumulates in the liver preferentially to 65Cu due to the preferential cellular entry of 63Cu and the impairment of the 63Cu exit by ceruloplasmin. The hepatic accumulation of monovalent 63Cu+ is likely to fuel the production of free radicals, which is potentially an explanation of the pathogenicity of WD. Altogether, the results suggest that the blood 65Cu/63Cu ratio recapitulates WD progression and is a potential prognostic biomarker of WD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{roblin_unusual_2020,

title = {The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties},

author = {Clarisse Roblin and Steve Chiumento and Olivier Bornet and Matthieu Nouailler and Christina S Müller and Katy Jeannot and Christian Basset and Sylvie Kieffer-Jaquinod and Yohann Couté and Stéphane Torelli and Laurent Le Pape and Volker Schünemann and Hamza Olleik and Bruno De La Villeon and Philippe Sockeel and Eric Di Pasquale and Cendrine Nicoletti and Nicolas Vidal and Leonora Poljak and Olga Iranzo and Thierry Giardina and Michel Fons and Estelle Devillard and Patrice Polard and Marc Maresca and Josette Perrier and Mohamed Atta and Françoise Guerlesquin and Mickael Lafond and Victor Duarte},

doi = {10.1073/pnas.2004045117},

issn = {1091-6490},

year  = {2020},

date = {2020-01-01},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

abstract = {The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sokolovska_using_2020,

title = {Using Unlabeled Data to Discover Bivariate Causality with Deep Restricted Boltzmann Machines},

author = {Nataliya Sokolovska and Olga Permiakova and Sofia K Forslund and Jean-Daniel Zucker},

doi = {10.1109/TCBB.2018.2879504},

issn = {1557-9964},

year  = {2020},

date = {2020-01-01},

journal = {IEEE/ACM transactions on computational biology and bioinformatics},

volume = {17},

number = {1},

pages = {358--364},

abstract = {An important question in microbiology is whether treatment causes changes in gut flora, and whether it also affects metabolism. The reconstruction of causal relations purely from non-temporal observational data is challenging. We address the problem of causal inference in a bivariate case, where the joint distribution of two variables is observed. We consider, in particular, data on discrete domains. The state-of-the-art causal inference methods for continuous data suffer from high computational complexity. Some modern approaches are not suitable for categorical data, and others need to estimate and fix multiple hyper-parameters. In this contribution, we introduce a novel method of causal inference which is based on the widely used assumption that if X causes Y, then P(X) and P(Y$backslash$textbarX) are independent. We propose to explore a semi-supervised approach where P(Y$backslash$textbarX) and P(X) are estimated from labeled and unlabeled data respectively, whereas the marginal probability is estimated potentially from much more (cheap unlabeled) data than the conditional distribution. We validate the proposed method on the standard cause-effect pairs. We illustrate by experiments on several benchmarks of biological network reconstruction that the proposed approach is very competitive in terms of computational time and accuracy compared to the state-of-the-art methods. Finally, we apply the proposed method to an original medical task where we study whether drugs confound human metagenome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{674,

title = {Software requirements for the analysis and interpretation of native ion mobility mass spectrometry data},

author = {T M Allison and P E Barran and J L P Benesch and S Cianferani and M T Degiacomi and V Gabelica and R Grandori and E G Marklund and T Menneteau and L G Migas and A Politis and M Sharon and F Sobott and K Thalassinos},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32649184},

doi = {10.1021/acs.analchem.9b05792},

issn = {1520-6882 (Electronic) 0003-2700 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Anal Chem},

note = {review, pas de projet LSMBO},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{673b,

title = {Computational strategies and challenges for using native ion mobility mass spectrometry in biophysics and structural biology},

author = {T M Allison and P E Barran and S Cianferani and M T Degiacomi and V Gabelica and R Grandori and E G Marklund and T Menneteau and L G Migas and A Politis and M Sharon and F Sobott and K Thalassinos and J L P Benesch},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32667808},

doi = {10.1021/acs.analchem.9b05791},

issn = {1520-6882 (Electronic) 0003-2700 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Anal Chem},

note = {review pas de projet LSMBO},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{663b,

title = {Middle Level IM-MS and CIU Experiments for Improved Therapeutic Immunoglobulin Subclass Fingerprinting},

author = {T Botzanowski and O Hernandez-Alba and M Malissard and E Wagner-Rousset and E Desligniere and O Colas and J F Haeuw and A Beck and S Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32453570},

doi = {10.1021/acs.analchem.0c00293},

issn = {1520-6882 (Electronic) 0003-2700 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Anal Chem},

volume = {92},

number = {13},

pages = {8827-8835},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1386,

title = {Computational strategies and challenges for using native ion mobility mass spectrometry in biophysics and structural biology},

author = {T. M. Allison and P. E. Barran and S. Cianferani and M. T. Degiacomi and V. Gabelica and R. Grandori and E. G. Marklund and T. Menneteau and L. G. Migas and A. Politis and M. Sharon and F. Sobott and K. Thalassinos and J. L. P. Benesch},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32667808},

doi = {10.1021/acs.analchem.9b05791},

issn = {1520-6882 (Electronic) 

0003-2700 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Anal Chem},

abstract = {Native mass spectrometry (MS) allows the interrogation of structural aspects of macromolecules in the gas phase, under the premise of having initially maintained their solution-phase non-covalent interactions intact. In the more than 25 years since the first reports, the utility of native MS has become well established in the structural biology community. The experimental and technological advances during this time have been rapid, resulting in dramatic increases in sensitivity, mass range, resolution, and complexity of possible experiments. As experimental methods are improved, there have been accompanying developments in computational approaches for analysing and exploiting the profusion of MS data in a structural and biophysical context. Here, based on discussions within the EU COST Action BM1403 on Native MS and Related Methods for Structural Biology with broad participation from Europe and North America, we consider the computational strategies currently being employed by the community, aspects of best practice, and the challenges that remain to be addressed.},

note = {review pas de projet LSMBO},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1556,

title = {Molecular determinants of MED1 interaction with the DNA bound VDR-RXR heterodimer},

author = {A. Y. Belorusova and M. Bourguet and S. Hessmann and S. Chalhoub and B. Kieffer and S. Cianferani and N. Rochel},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32990725},

doi = {10.1093/nar/gkaa775},

issn = {1362-4962 (Electronic) 

0305-1048 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Nucleic Acids Res},

volume = {48},

number = {19},

pages = {11199-11213},

abstract = {The MED1 subunit of the Mediator complex is an essential coactivator of nuclear receptor-mediated transcriptional activation. While structural requirements for ligand-dependent binding of classical coactivator motifs of MED1 to numerous nuclear receptor ligand-binding domains have been fully elucidated, the recognition of the full-length or truncated coactivator by full nuclear receptor complexes remain unknown. Here we present structural details of the interaction between a large part of MED1 comprising its structured N-terminal and the flexible receptor-interacting domains and the mutual heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) bound to their cognate DNA response element. Using a combination of structural and biophysical methods we show that the ligand-dependent interaction between VDR and the second coactivator motif of MED1 is crucial for complex formation and we identify additional, previously unseen, interaction details. In particular, we identified RXR regions involved in the interaction with the structured N-terminal domain of MED1, as well as VDR regions outside the classical coactivator binding cleft affected by coactivator recruitment. These findings highlight important roles of each receptor within the heterodimer in selective recognition of MED1 and contribute to our understanding of the nuclear receptor-coregulator complexes.},

note = {2017/13},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1507,

title = {Quantification of biomarkers for beef meat qualities using a combination of Parallel Reaction Monitoring- and antibody-based proteomics},

author = {M. Bonnet and J. Soulat and J. Bons and S. Leger and L. De Koning and C. Carapito and B. Picard},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32078991},

doi = {10.1016/j.foodchem.2020.126376},

issn = {1873-7072 (Electronic) 

0308-8146 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Food Chem},

volume = {317},

pages = {126376},

abstract = {We and others have identified biomarker candidates of tenderness or marbling, two major attributes of bovine meat-eating qualities for consumers' satisfaction. In this study, Reverse Phase Protein Arrays (RPPA) and targeted mass spectrometry assays using Parallel Reaction Monitoring (PRM) were developed to test whether 10 proteins pass the sequential qualification and verification steps of the challenging biomarker discovery pipeline. At least MYH1, TPI1, ALDH1A1 and CRYAB were qualified by RPPA or PRM as being differentially abundant according to marbling values of longissimus thoracis and semimembranosus muscles. Significant mathematical relationships between the individual abundance of each of the four proteins and marbling values were verified by linear or logistic regressions. Four proteins, TNNT1, MDH1, PRDX6 and ENO3 were qualified and verified for tenderness, and the abundance of MDH1 explained 49% of the tenderness variability. The present PRM and RPPA results pave the way for development of useful meat industrial multiplex-proteins assays.},

note = {2017/14},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1390,

title = {Middle Level IM-MS and CIU Experiments for Improved Therapeutic Immunoglobulin Subclass Fingerprinting},

author = {T. Botzanowski and O. Hernandez-Alba and M. Malissard and E. Wagner-Rousset and E. Desligniere and O. Colas and J. F. Haeuw and A. Beck and S. Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32453570},

doi = {10.1021/acs.analchem.0c00293},

issn = {1520-6882 (Electronic) 

0003-2700 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Anal Chem},

volume = {92},

number = {13},

pages = {8827-8835},

abstract = {Most of the current FDA and EMA approved therapeutic monoclonal antibodies (mAbs) are based on humanized or human IgG1, 2, or 4 subclasses and engineered variants. On the structural side, these subclasses are characterized by specific interchain disulfide bridge connections. Different analytical techniques have been reported to assess intact IgGs subclasses, with recently special interest in native ion mobility (IM) and collision induced unfolding (CIU) mass spectrometry (MS). However, these two techniques exhibit significant limitations to differentiate mAb subclasses at the intact level. In the present work, we aimed at developing a unique IM-MS-based approach for the characterization of mAb subclasses at the middle level. Upon IdeS-digestion, the unfolding patterns of the F(ab')2 and Fc domains were simultaneously analyzed in a single run to provide deeper structural insights of the mAb scaffold. The unfolding patterns associated with the F(ab')2 domains are completely different in terms of unfolding energies and number of transitions. Thereby, F(ab')2 regions are the diagnostic domain to provide specific unfolding signatures to differentiate IgG subclasses and provide more confident subclass categorization than CIU on intact mAbs. In addition, the potential of middle-level CIU was evaluated through the characterization of eculizumab, a hybrid therapeutic IgG2/4 mAb. The unfolding signatures of both domains were allowed to corroborate, within a single run, the hybrid nature of eculizumab as well as specific subclass domain assignments to the F(ab')2 and Fc regions. Altogether, our results confirm the suitability of middle-level CIU of F(ab')2 domains for subclass categorization of canonical and more complex new generation engineered antibodies and related products.},

note = {2016/13},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1396,

title = {Proline: an efficient and user-friendly software suite for large-scale proteomics},

author = {D. Bouyssie and A. M. Hesse and E. Mouton-Barbosa and M. Rompais and C. Macron and C. Carapito and A. Gonzalez de Peredo and Y. Coute and V. Dupierris and A. Burel and J. P. Menetrey and A. Kalaitzakis and J. Poisat and A. Romdhani and O. Burlet-Schiltz and S. Cianferani and J. Garin and C. Bruley},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32096818},

doi = {10.1093/bioinformatics/btaa118},

issn = {1367-4811 (Electronic) 

1367-4803 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Bioinformatics},

volume = {36},

number = {10},

pages = {3148-3155},

abstract = {MOTIVATION: The proteomics field requires the production and publication of reliable mass spectrometry-based identification and quantification results. Although many tools or algorithms exist, very few consider the importance of combining, in a unique software environment, efficient processing algorithms and a data management system to process and curate hundreds of datasets associated with a single proteomics study. RESULTS: Here, we present Proline, a robust software suite for analysis of MS-based proteomics data, which collects, processes and allows visualization and publication of proteomics datasets. We illustrate its ease of use for various steps in the validation and quantification workflow, its data curation capabilities and its computational efficiency. The DDA label-free quantification workflow efficiency was assessed by comparing results obtained with Proline to those obtained with a widely used software using a spiked-in sample. This assessment demonstrated Proline's ability to provide high quantification accuracy in a user-friendly interface for datasets of any size. AVAILABILITY AND IMPLEMENTATION: Proline is available for Windows and Linux under CECILL open-source license. It can be deployed in client-server mode or in standalone mode at http://proline.profiproteomics.fr/#downloads. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},

note = {2012/16},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1536,

title = {Specific shifts in the endocannabinoid system in hibernating brown bears},

author = {C. Boyer and L. Cussonneau and C. Brun and C. Deval and J. P. Pais de Barros and S. Chanon and N. Bernoud-Hubac and P. Daira and A. L. Evans and J. M. Arnemo and J. E. Swenson and G. Gauquelin-Koch and C. Simon and S. Blanc and L. Combaret and F. Bertile and E. Lefai},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33292302},

doi = {10.1186/s12983-020-00380-y},

issn = {1742-9994 (Print) 

1742-9994 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Front Zool},

volume = {17},

number = {1},

pages = {35},

abstract = {In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. In hibernating brown bears (Ursus arctos), we hypothesized that beyond an overall suppression of the ECS, seasonal shift in endocannabinoids compounds could be linked to bear's peculiar features that include hibernation without arousal episodes and capacity to react to external disturbance. We explored circulating lipids in serum and the ECS in plasma and metabolically active tissues in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid C22:6 n-3 and a decrease in arachidonic acid C20:4 n-6. In adipose and muscle tissues of hibernating bears, we found significant lower concentrations of 2-arachidonoylglycerol (2-AG), a major ligand of cannabinoid receptors 1 (CB1) and 2 (CB2). Lower mRNA level for genes encoding CB1 and CB2 were also found in winter muscle and adipose tissue, respectively. The observed reduction in ECS tone may promote fatty acid mobilization from body fat stores, and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating level of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the conservation of an anorexigenic signal and in the maintenance of torpor during hibernation, while sustaining the capacity of bears to sense stimuli from the environment.},

note = {2011/34},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1502,

title = {NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation, and hyperinflammation},

author = {C. N. Castro and M. Rosenzwajg and R. Carapito and M. Shahrooei and M. Konantz and A. Khan and Z. Miao and M. Gross and T. Tranchant and M. Radosavljevic and N. Paul and T. Stemmelen and F. Pitoiset and A. Hirschler and B. Nespola and A. Molitor and V. Rolli and A. Pichot and L. E. Faletti and B. Rinaldi and S. Friant and M. Mednikov and H. Karauzum and M. J. Aman and C. Carapito and C. Lengerke and V. Ziaee and W. Eyaid and S. Ehl and F. Alroqi and N. Parvaneh and S. Bahram},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32766723},

doi = {10.1084/jem.20192275},

issn = {1540-9538 (Electronic) 

0022-1007 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {J Exp Med},

volume = {217},

number = {12},

abstract = {The Nck-associated protein 1-like (NCKAP1L) gene, alternatively called hematopoietic protein 1 (HEM-1), encodes a hematopoietic lineage-specific regulator of the actin cytoskeleton. Nckap1l-deficient mice have anomalies in lymphocyte development, phagocytosis, and neutrophil migration. Here we report, for the first time, NCKAP1L deficiency cases in humans. In two unrelated patients of Middle Eastern origin, recessive mutations in NCKAP1L abolishing protein expression led to immunodeficiency, lymphoproliferation, and hyperinflammation with features of hemophagocytic lymphohistiocytosis. Immunophenotyping showed an inverted CD4/CD8 ratio with a major shift of both CD4+ and CD8+ cells toward memory compartments, in line with combined RNA-seq/proteomics analyses revealing a T cell exhaustion signature. Consistent with the core function of NCKAP1L in the reorganization of the actin cytoskeleton, patients' T cells displayed impaired early activation, immune synapse morphology, and leading edge formation. Moreover, knockdown of nckap1l in zebrafish led to defects in neutrophil migration. Hence, NCKAP1L mutations lead to broad immune dysregulation in humans, which could be classified within actinopathies.},

note = {2017/08},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1399,

title = {VHH characterization.Recombinant VHHs: Production, characterization and affinity},

author = {E. Chabrol and J. Stojko and A. Nicolas and T. Botzanowski and B. Fould and M. Antoine and S. Cianferani and G. Ferry and J. A. Boutin},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31676284},

doi = {10.1016/j.ab.2019.113491},

issn = {1096-0309 (Electronic) 

0003-2697 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Anal Biochem},

volume = {589},

pages = {113491},

abstract = {Among the biological approaches to therapeutics, are the cells, such as CAR-T cells engineered or not, the antibodies armed or not, and the smaller protein scaffolds that can be modified to render them specific of other proteins, a la facon of antibodies. For several years, we explored ways to substitute antibodies by nanobodies (also known as VHHs), the smallest recognizing part of camelids' heavy-chain antibodies: production of those small proteins in host microorganisms, minute analyses, characterization, and qualification of their affinity towards designed targets. Here, we present three standard VHHs described in the literature: anti-albumin, anti-EGF receptor and anti-HER2, a typical cancer cell surface -associated protein. Because they differ slightly in global structure, they are good models to assess our body of analytical methodologies. The VHHs were expressed in several bacteria strains in order to identify and overcome the bottlenecks to obtain homogeneous preparations of this protein. A large panel of biophysical tools, ranging from spectroscopy to mass spectrometry, was here combined to assess VHH structural features and the impact of the disulfide bond. The routes are now ready to move to more complex VHHs raised against specific targets in numerous areas including oncology.},

note = {2016/04},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1505,

title = {Optimal conditions for tandem mass spectrometric sequencing of information-containing nitrogen-substituted polyurethanes},

author = {L. Charles and T. Mondal and V. Greff and M. Razzini and V. Monnier and A. Burel and C. Carapito and J. F. Lutz},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32311797},

doi = {10.1002/rcm.8815},

issn = {1097-0231 (Electronic) 

0951-4198 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Rapid Commun Mass Spectrom},

volume = {34},

number = {14},

pages = {e8815},

abstract = {RATIONALE: To prevent solubility issues faced with sequence-defined polyurethanes, a new family of digital polyurethanes was conceived with the alkyl coding chain held by the carbamate nitrogen (N) atom and CH3 instead of OH as the varpi termination. This led to different dissociation mechanisms that were explored prior to optimizing tandem mass spectrometric (MS/MS) sequencing. METHODS: N-Substituted polyurethanes (N-R PUs) were dissolved in methanol and subjected to collision-induced dissociation (CID) as deprotonated chains in the negative ion mode, and as ammonium and sodium adducts in the positive ion mode, using electrospray ionization (ESI) as the ionization technique. Their dissociation behavior was thoroughly investigated using a quadrupole time-of-flight (QTOF) instrument in order to provide accurate mass measurements to support proposed fragmentation mechanisms. RESULTS: While O-(CO) bonds were broken in N-H PUs, the CH2 -O linkage between repeating units was cleaved upon CID of N-R PUs. This main process occurred either from deprotonated molecules or from cationized chains but was followed by different rearrangements, producing up to four product ion series. Yet, MS/MS spectra could be drastically simplified for precursor ions having their acidic alpha group methylated, as was found to spontaneously occur upon storage in methanol. CONCLUSIONS: Using experimental conditions aimed at avoiding any reactive proton in precursor ions (no acidic end-groups and alkali adduction), full coverage sequence of N-R PUs was successfully achieved with the single ion series observed in MS/MS, opening a promising perspective for reading large amounts of information stored in these dyad-encoded polymers.},

note = {pas de numéro de projet},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1558,

title = {Toward Automation of Collision-Induced Unfolding Experiments through Online Size Exclusion Chromatography Coupled to Native Mass Spectrometry},

author = {E. Desligniere and A. Ehkirch and T. Botzanowski and A. Beck and O. Hernandez-Alba and S. Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32886492},

doi = {10.1021/acs.analchem.0c01426},

issn = {1520-6882 (Electronic) 

0003-2700 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Anal Chem},

volume = {92},

number = {19},

pages = {12900-12908},

abstract = {Ion mobility (IM)-based collision-induced unfolding (CIU) has gained increasing attention to probe gas-phase unfolding of proteins and their noncovalent complexes, notably for biotherapeutics. CIU detects subtle conformational changes of proteins and emerges as an attractive alternative to circumvent poor IM resolution. However, CIU still lacks in automation for buffer exchange and data acquisition, precluding its wide adoption. We present here an automated workflow for CIU experiments, from sample preparation to data interpretation using online size exclusion chromatography coupled to native IM mass spectrometry (SEC-CIU). Online automated SEC-CIU experiments offer several benefits over nanoESI-CIU, among which are (i) improved and fast desalting compared to manual buffer exchange used for classical CIU experiments; (ii) drastic reduction of the overall data collection time process; and (iii) maintaining the number of unfolding transitions. We then evaluate the potential of SEC-CIU to distinguish monoclonal antibody (mAb) subclasses, illustrating the efficiency of our method for rapid mAb subclass identification at both intact and middle levels. Finally, we demonstrate that CIU data acquisition time can be further reduced either by setting up a scheduled CIU method relying on diagnostic trap collision voltages or by implementing mAb-multiplexed SEC-CIU analyses to maximize information content in a single experiment. Altogether, our results confirm the suitability of SEC-CIU to automate CIU experiments, particularly for the fast characterization of next-generation mAb-based products.},

note = {2016/13},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1391,

title = {Glycan-Mediated Technology for Obtaining Homogeneous Site-Specific Conjugated Antibody-Drug Conjugates: Synthesis and Analytical Characterization by Using Complementary Middle-up LC/HRMS Analysis},

author = {B. L. Duivelshof and E. Desligniere and O. Hernandez-Alba and A. Ehkirch and H. Toftevall and J. Sjogren and S. Cianferani and A. Beck and D. Guillarme and V. D'Atri},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32407621},

doi = {10.1021/acs.analchem.0c00282},

issn = {1520-6882 (Electronic) 

0003-2700 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Anal Chem},

volume = {92},

number = {12},

pages = {8170-8177},

abstract = {Conventional antibody-drug conjugate (ADC) manufacturing methods are based on the nonselective bioconjugation of cytotoxic drugs to lysine and cysteine residues. This results in highly heterogeneous mixtures of different drug-antibody ratios (DAR) that can significantly affect the safety and efficacy of the ADC product. Recently, an innovative procedure named GlyCLICK was suggested, consisting of a two-step enzymatic procedure to transform Fc-glycans present on IgG mAbs into two site-specific anchor points for the conjugation of any alkyne-containing payload of choice. Here, we evaluated the conjugation process by comparing trastuzumab and trastuzumab conjugated with DM1, following the GlyCLICK procedure. Complementary reversed phase liquid chromatography (RPLC) and hydrophilic interaction chromatography (HILIC) coupled to high-resolution mass spectrometry (HRMS) were used to analyze the protein subunits (ca. 25-100 kDa) obtained after different levels of enzymatic digestion and chemical reduction. Our results demonstrated that the hydrophobic character of the drug molecule allows to rapidly confirm the Fc-drug conjugation at the chromatographic level. Furthermore, the hyphenation to MS detection provided accurate mass information on the ADC subunits and facilitated the DAR determination of 2.0. Therefore, this work illustrates how middle-up analysis using LC/HRMS can provide accurate and complementary information on the critical quality attributes of these novel site-specific ADC products.},

note = {pas de numéro de projet car pas de manips LSMBO},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1400,

title = {Analysis of ADCs by Native Mass Spectrometry},

author = {O. Hernandez-Alba and A. Ehkirch and A. Beck and S. Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31643058},

doi = {10.1007/978-1-4939-9929-3_13},

issn = {1940-6029 (Electronic) 

1064-3745 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Methods Mol Biol},

volume = {2078},

pages = {197-211},

abstract = {Mass spectrometry performed in nondenaturing conditions (native MS) has proven its utility for the quantitative and qualitative analysis of antibody-drug conjugates (ADCs), especially when ADCs' subunits involve noncovalent interactions (i.e., cysteine-conjugated ADCs). Its hyphenation to ion mobility spectrometry (IM-MS) allows differentiation of gas-phase ions based on their rotationally averaged collision cross section providing an additional dimension of conformational characterization of ADCs. More recently, size exclusion chromatography (SEC) appeared as an interesting technique to perform online buffer exchange in an automated way prior to native MS/IM-MS analysis. Online SEC-native MS/IM-MS allows the global structural characterization of ADCs and the assessment of some critical quality attributes (CQAs) required for ADC release on the market, such as drug load distribution (DLD), drug-to-antibody ratio (DAR), the average DAR (DARav), and the relative amount of unconjugated mAb.},

note = {review},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1397,

title = {(Thia)calixarenephosphonic Acids as Potent Inhibitors of the Nucleic Acid Chaperone Activity of the HIV-1 Nucleocapsid Protein with a New Binding Mode and Multitarget Antiviral Activity},

author = {N. Humbert and L. Kovalenko and F. Saladini and A. Giannini and M. Pires and T. Botzanowski and S. Cherenok and C. Boudier and K. K. Sharma and E. Real and O. A. Zaporozhets and S. Cianferani and C. Seguin-Devaux and F. Poggialini and M. Botta and M. Zazzi and V. I. Kalchenko and M. Mori and Y. Mely},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32045204},

doi = {10.1021/acsinfecdis.9b00290},

issn = {2373-8227 (Electronic) 

2373-8227 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {ACS Infect Dis},

volume = {6},

number = {4},

pages = {687-702},

abstract = {The nucleocapsid protein (NC) is a highly conserved protein that plays key roles in HIV-1 replication through its nucleic acid chaperone properties mediated by its two zinc fingers and basic residues. NC is a promising target for antiviral therapy, particularly to control viral strains resistant to currently available drugs. Since calixarenes with antiviral properties have been described, we explored the ability of calixarene hydroxymethylphosphonic or sulfonic acids to inhibit NC chaperone properties and exhibit antiviral activity. By using fluorescence-based assays, we selected four calixarenes inhibiting NC chaperone activity with submicromolar IC50 values. These compounds were further shown by mass spectrometry, isothermal titration calorimetry, and fluorescence anisotropy to bind NC with no zinc ejection and to compete with nucleic acids for the binding to NC. Molecular dynamic simulations further indicated that these compounds interact via their phosphonate or sulfonate groups with the basic surface of NC but not with the hydrophobic plateau at the top of the folded fingers. Cellular studies showed that the most soluble compound CIP201 inhibited the infectivity of wild-type and drug-resistant HIV-1 strains at low micromolar concentrations, primarily targeting the early steps of HIV-1 replication. Moreover, CIP201 was also found to inhibit the flipping and polymerization activity of reverse transcriptase. Calixarenes thus form a class of noncovalent NC inhibitors, endowed with a new binding mode and multitarget antiviral activity.},

note = {2017/04},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{679b,

title = {NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation, and hyperinflammation},

author = {C N Castro and M Rosenzwajg and R Carapito and M Shahrooei and M Konantz and A Khan and Z Miao and M Gross and T Tranchant and M Radosavljevic and N Paul and T Stemmelen and F Pitoiset and A Hirschler and B Nespola and A Molitor and V Rolli and A Pichot and L E Faletti and B Rinaldi and S Friant and M Mednikov and H Karauzum and M J Aman and C Carapito and C Lengerke and V Ziaee and W Eyaid and S Ehl and F Alroqi and N Parvaneh and S Bahram},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32766723},

doi = {10.1084/jem.20192275},

issn = {1540-9538 (Electronic) 0022-1007 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {J Exp Med},

volume = {217},

number = {12},

note = {????},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{659,

title = {VHH characterization.Recombinant VHHs: Production, characterization and affinity},

author = {E Chabrol and J Stojko and A Nicolas and T Botzanowski and B Fould and M Antoine and S Cianferani and G Ferry and J A Boutin},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31676284},

doi = {10.1016/j.ab.2019.113491},

issn = {1096-0309 (Electronic) 0003-2697 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Anal Biochem},

volume = {589},

pages = {113491},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{678,

title = {Optimal conditions for tandem mass spectrometric sequencing of information-containing nitrogen-substituted polyurethanes},

author = {L Charles and T Mondal and V Greff and M Razzini and V Monnier and A Burel and C Carapito and J F Lutz},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32311797},

doi = {10.1002/rcm.8815},

issn = {1097-0231 (Electronic) 0951-4198 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Rapid Commun Mass Spectrom},

volume = {34},

number = {14},

pages = {e8815},

note = {????},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{666,

title = {Abeta(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage},

author = {S Ciudad and E Puig and T Botzanowski and M Meigooni and A S Arango and J Do and M Mayzel and M Bayoumi and S Chaignepain and G Maglia and S Cianferani and V Orekhov and E Tajkhorshid and B Bardiaux and N Carulla},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32541820},

doi = {10.1038/s41467-020-16566-1},

issn = {2041-1723 (Electronic) 2041-1723 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Nat Commun},

volume = {11},

number = {1},

pages = {3014},

note = {2018/12},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{667,

title = {On the use of DNA as a linker in antibody-drug conjugates: synthesis, stability and in vitro potency},

author = {I Dovgan and A Ehkirch and V Lehot and I Kuhn and O Koniev and S Kolodych and A Hentz and M Ripoll and S Ursuegui and M Nothisen and S Cianferani and A Wagner},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32376903},

doi = {10.1038/s41598-020-64518-y},

issn = {2045-2322 (Electronic) 2045-2322 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Sci Rep},

volume = {10},

number = {1},

pages = {7691},

note = {2019-05},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{668b,

title = {Glycan-Mediated Technology for Obtaining Homogeneous Site-Specific Conjugated Antibody-Drug Conjugates: Synthesis and Analytical Characterization by Using Complementary Middle-up LC/HRMS Analysis},

author = {B L Duivelshof and E Desligniere and O Hernandez-Alba and A Ehkirch and H Toftevall and J Sjogren and S Cianferani and A Beck and D Guillarme and V D'Atri},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32407621},

doi = {10.1021/acs.analchem.0c00282},

issn = {1520-6882 (Electronic) 0003-2700 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Anal Chem},

volume = {92},

number = {12},

pages = {8170-8177},

note = {pas de manips au LSMBO},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{655,

title = {Homogeneous antibody-drug conjugates: DAR 2 anti-HER2 obtained by conjugation on isolated light chain followed by mAb assembly},

author = {M Farras and J Miret and M Camps and R Roman and O Martinez and X Pujol and S Erb and A Ehkirch and S Cianferani and A Casablancas and J J Cairo},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31876436},

doi = {10.1080/19420862.2019.1702262},

issn = {1942-0870 (Electronic) 1942-0862 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {MAbs},

volume = {12},

number = {1},

pages = {1702262},

note = {2018/06},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{656,

title = {Analysis of ADCs by Native Mass Spectrometry},

author = {O Hernandez-Alba and A Ehkirch and A Beck and S Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31643058},

doi = {10.1007/978-1-4939-9929-3_13},

issn = {1940-6029 (Electronic) 1064-3745 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Methods Mol Biol},

volume = {2078},

pages = {197-211},

note = {review},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{658,

title = {(Thia)calixarenephosphonic Acids as Potent Inhibitors of the Nucleic Acid Chaperone Activity of the HIV-1 Nucleocapsid Protein with a New Binding Mode and Multitarget Antiviral Activity},

author = {N Humbert and L Kovalenko and F Saladini and A Giannini and M Pires and T Botzanowski and S Cherenok and C Boudier and K K Sharma and E Real and O A Zaporozhets and S Cianferani and C Seguin-Devaux and F Poggialini and M Botta and M Zazzi and V I Kalchenko and M Mori and Y Mely},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32045204},

doi = {10.1021/acsinfecdis.9b00290},

issn = {2373-8227 (Electronic) 2373-8227 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {ACS Infect Dis},

volume = {6},

number = {4},

pages = {687-702},

abstract = {The nucleocapsid protein (NC) is a highly conserved protein that plays key roles in HIV-1 replication through its nucleic acid chaperone properties mediated by its two zinc fingers and basic residues. NC is a promising target for antiviral therapy, particularly to control viral strains resistant to currently available drugs. Since calixarenes with antiviral properties have been described, we explored the ability of calixarene hydroxymethylphosphonic or sulfonic acids to inhibit NC chaperone properties and exhibit antiviral activity. By using fluorescence-based assays, we selected four calixarenes inhibiting NC chaperone activity with submicromolar IC50 values. These compounds were further shown by mass spectrometry, isothermal titration calorimetry, and fluorescence anisotropy to bind NC with no zinc ejection and to compete with nucleic acids for the binding to NC. Molecular dynamic simulations further indicated that these compounds interact via their phosphonate or sulfonate groups with the basic surface of NC but not with the hydrophobic plateau at the top of the folded fingers. Cellular studies showed that the most soluble compound CIP201 inhibited the infectivity of wild-type and drug-resistant HIV-1 strains at low micromolar concentrations, primarily targeting the early steps of HIV-1 replication. Moreover, CIP201 was also found to inhibit the flipping and polymerization activity of reverse transcriptase. Calixarenes thus form a class of noncovalent NC inhibitors, endowed with a new binding mode and multitarget antiviral activity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{675,

title = {Effectiveness of Resistive Vibration Exercise and Whey Protein Supplementation Plus Alkaline Salt on the Skeletal Muscle Proteome Following 21 Days of Bed Rest in Healthy Males},

author = {H C Kenny and G Tascher and A Ziemianin and F Rudwill and A Zahariev and I Chery and G Gauquelin-Koch and M P Barielle and M Heer and S Blanc and D J O'Gorman and F Bertile},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32609523},

doi = {10.1021/acs.jproteome.0c00256},

issn = {1535-3907 (Electronic) 1535-3893 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {J Proteome Res},

volume = {19},

number = {8},

pages = {3438-3451},

note = {2011/34},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{661,

title = {Growth and differentiation factor 15 is secreted by skeletal muscle during exercise and promotes lipolysis in humans},

author = {C Laurens and A Parmar and E Murphy and D Carper and B Lair and P Maes and J Vion and N Boulet and C Fontaine and M Marquès and D Larrouy and I Harant and C Thalamas and E Montastier and S Caspar-Baugil and V Bourlier and G Tavernier and J L Grolleau and A Bouloumié and D Langin and N Viguerie and F Bertile and S Blanc and I De Glisezinski and D O’Gorman and C Moro},

year  = {2020},

date = {2020-01-01},

journal = {JCI Insight},

volume = {5},

number = {6},

pages = {E131870},

note = {2016/26},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{664b,

title = {Effects of topical corticosteroids and lidocaine on Borrelia burgdorferi sensu lato in mouse skin: potential impact to human clinical trials},

author = {B Lefeuvre and P Cantero and L Ehret-Sabatier and C Lenormand and C Barthel and C Po and N Parveen and A Grillon and B Jaulhac and N Boulanger},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32601348},

doi = {10.1038/s41598-020-67440-5},

issn = {2045-2322 (Electronic) 2045-2322 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Sci Rep},

volume = {10},

number = {1},

pages = {10552},

note = {2012/30},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{665b,

title = {MicroRNAs facilitate skeletal muscle maintenance and metabolic suppression in hibernating brown bears},

author = {B E Luu and E Lefai and S Giroud and J E Swenson and B Chazarin and G Gauquelin-Koch and J M Arnemo and A L Evans and F Bertile and K B Storey},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31643088},

doi = {10.1002/jcp.29294},

issn = {1097-4652 (Electronic) 0021-9541 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {J Cell Physiol},

volume = {235},

number = {4},

pages = {3984-3993},

note = {2011/34},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{662,

title = {Phenotypic Adaption of Pseudomonas aeruginosa by Hacking Siderophores Produced by Other Microorganisms},

author = {Q Perraud and P Cantero and B Roche and V Gasser and V P Normant and L Kuhn and P Hammann and G L A Mislin and L Ehret-Sabatier and I J Schalk},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32024770},

doi = {10.1074/mcp.RA119.001829},

issn = {1535-9484 (Electronic) 1535-9476 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Mol Cell Proteomics},

volume = {19},

number = {4},

pages = {589-607},

note = {2015/28},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669b,

title = {Probing Protein Interaction Networks by Combining MS-Based Proteomics and Structural Data Integration},

author = {G Postic and J Marcoux and V Reys and J Andreani and Y Vandenbrouck and M P Bousquet and E Mouton-Barbosa and S Cianferani and O Burlet-Schiltz and R Guerois and G Labesse and P Tuffery},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32338910},

doi = {10.1021/acs.jproteome.0c00066},

issn = {1535-3907 (Electronic) 1535-3893 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {J Proteome Res},

volume = {19},

number = {7},

pages = {2807-2820},

note = {pas de projet, pas de manips au labo},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{670b,

title = {Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways},

author = {M Sabou and C Doderer-Lang and C Leyer and A Konjic and S Kubina and S Lennon and O Rohr and S Viville and S Cianferani and E Candolfi and A W Pfaff and J Brunet},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31492965},

doi = {10.1007/s00018-019-03267-2},

issn = {1420-9071 (Electronic) 1420-682X (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Cell Mol Life Sci},

volume = {77},

number = {11},

pages = {2141-2156},

keywords = {},

pubstate = {published},

tppubtype = {article}

}