@article{671b,

title = {Investigating Ugi / Passerini multicomponent reactions for the Site-Selective Conjugation of Native Trastuzumab},

author = {C Sornay and S Hessmann and S Erb and I Dovgan and A Ehkirch and T Botzanowski and S Cianferani and A Wagner and G Chaubet},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32588934},

doi = {10.1002/chem.202002432},

issn = {1521-3765 (Electronic) 0947-6539 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Chemistry},

note = {2018/30},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{677,

title = {Tenascin-C Orchestrates an Immune-Suppressive Tumor Microenvironment in Oral Squamous Cell Carcinoma},

author = {C Spenle and T Loustau and D Murdamoothoo and W Erne and S Beghelli-de Forest Divonne and R Veber and L Petti and P Bourdely and M Morgelin and E M Brauchle and G Cremel and V Randrianarisoa and A Camara and S Rekima and S Schaub and K Nouhen and T Imhof and U Hansen and N Paul and R Carapito and N Pythoud and A Hirschler and C Carapito and H Dumortier and C G Mueller and M Koch and K Schenke-Layland and S Kon and A Sudaka and F Anjuere and E Van Obberghen-Schilling and G Orend},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32665262},

doi = {10.1158/2326-6066.CIR-20-0074},

issn = {2326-6074 (Electronic) 2326-6066 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Cancer Immunol Res},

note = {????},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{672b,

title = {Ethynylation of Cysteine Residues: From Peptides to Proteins in Vitro and in Living Cells},

author = {R Tessier and R K Nandi and B G Dwyer and D Abegg and C Sornay and J Ceballos and S Erb and S Cianferani and A Wagner and G Chaubet and A Adibekian and J Waser},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32233093},

doi = {10.1002/anie.202002626},

issn = {1521-3773 (Electronic) 1433-7851 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Angew Chem Int Ed Engl},

volume = {59},

number = {27},

pages = {10961-10970},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{676,

title = {Phylogenomic Classification and Biosynthetic Potential of the Fossil Fuel-Biodesulfurizing Rhodococcus Strain IGTS8},

author = {D Thompson and V Cognat and M Goodfellow and S Koechler and D Heintz and C Carapito and A Van Dorsselaer and H Mahmoud and V Sangal and W Ismail},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32733398},

doi = {10.3389/fmicb.2020.01417},

issn = {1664-302X (Print) 1664-302X (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Front Microbiol},

volume = {11},

pages = {1417},

note = {???},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{642,

title = {Determination of size variants by CE-SDS for approved therapeutic antibodies: Key implications of subclasses and light chain specificities},

author = {E Wagner and O Colas and S Chenu and A Goyon and A Murisier and S Cianferani and Y Francois and S Fekete and D Guillarme and V D'Atri and A Beck},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32113118},

doi = {10.1016/j.jpba.2020.113166},

issn = {1873-264X (Electronic) 0731-7085 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {J Pharm Biomed Anal},

volume = {184},

pages = {113166},

note = {pas de manip MS},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{660,

title = {Drug Loading and Distribution of ADCs After Reduction or IdeS Digestion and Reduction},

author = {E Wagner-Rousset and O Colas and Y N Francois and S Heinisch and D Guillarme and S Cianferani and A Beck},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31643057},

doi = {10.1007/978-1-4939-9929-3_12},

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

year  = {2020},

date = {2020-01-01},

journal = {Methods Mol Biol},

volume = {2078},

pages = {187-195},

note = {pas de manip MS LSMBO},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{641b,

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 = {???},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{643b,

title = {Alterations in rat adipose tissue transcriptome and proteome in response to prolonged fasting.},

author = {M Ibrahim and D Ayoub and T Wasselin and A Van Dorsselaer and Y Le Maho and T Raclot and F Bertile},

year  = {2020},

date = {2020-01-01},

journal = {Biological Chemistry},

volume = {401},

number = {3},

pages = {389-405},

note = {2009/41},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{691,

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 = {Belorusova, Anna Y 

Bourguet, Maxime 

Hessmann, Steve 

Chalhoub, Sandra 

Kieffer, Bruno 

Cianferani, Sarah 

Rochel, Natacha 

eng 

Research Support, Non-U.S. Gov't 

England 

2020/09/30 06:00 

Nucleic Acids Res. 2020 Nov 4;48(19):11199-11213. doi: 10.1093/nar/gkaa775.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{654,

title = {Skin Interface, a Key Player for Borrelia Multiplication and Persistence in Lyme Borreliosis},

author = {Q Bernard and A Grillon and C Lenormand and L Ehret-Sabatier and N Boulanger},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32007396},

doi = {10.1016/j.pt.2019.12.017},

issn = {1471-5007 (Electronic) 

1471-4922 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Trends Parasitol},

volume = {36},

number = {3},

pages = {304-314},

abstract = {The skin plays a key role in vector-borne diseases because it is the site where the arthropod coinoculates pathogens and its saliva. Lyme borreliosis, particularly well investigated in this context, is a multisystemic infectious disease caused by Borrelia burgdorferi sensu lato and transmitted by the hard tick Ixodes. Numerous in vitro studies were conducted to better understand the role of specific skin cells and tick saliva in host defense, vector feeding, and pathogen transmission. The skin was also evidenced in various animal models as the site of bacterial multiplication and persistence. We present the achievements in this field as well as the gaps that impede comprehensive knowledge of the disease pathophysiology and the development of efficient diagnostic tools and vaccines in humans.},

note = {2012/30},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{680,

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 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{694,

title = {The longer the worse: a combined proteomic and targeted study of the long-termversusshort-term effects of silver nanoparticles on macrophages},

author = {B Dalzon and C Aude-Garcia and H Diemer and J Bons and C Marie-Desvergne and J Perard and M Dubosson and V Collin-Faure and C Carapito and S Sanglier-Cianferani and M Carriere and T Rabilloud},

url = {<Go to ISI>://WOS:000549099000010},

doi = {10.1039/c9en01329f},

issn = {2051-8153},

year  = {2020},

date = {2020-01-01},

journal = {Environmental Science-Nano},

volume = {7},

number = {7},

pages = {2032-2046},

abstract = {Despite considerable research effort devoted to the study of the effects of silver nanoparticles on mammalian cells in recent years, data on the potential long term effects of this nanomaterial remain scarce, and centered on epithelial cells. The aim of this study was to explore the effects of silver nanoparticles on macrophages. To this end, RAW 264.7 murine macrophages were exposed to either 1 mu g ml(-1)silver nanoparticles for 20 days,i.e.a chronic exposure scheme, or to 20 mu g ml(-1)silver nanoparticles for 24 hours,i.e.an acute exposure scheme. A proteomic study was then conducted to study and compare the cellular responses to both exposure schemes. They proved to be essentially different, and stronger for the chronic exposure scheme. Targeted validation studies showed effects of chronic exposure to silver nanoparticles on detoxifying enzymes such as flavin reductase, which was increased, and on central metabolism enzymes such as triose phosphate isomerase, the activity of which decreased under chronic exposure to silver nanoparticles. Chronic exposure to silver nanoparticles also induced a decrease of reduced glutathione content, a decreased phagocytic activity and reduced macrophage responses to lipopolysaccharide, as exemplified by nitric oxide and interleukin 6 production. Overall, chronic exposure to silver nanoparticles induced stronger effects than acute exposure on macrophages in the metabolic (glutathione level, mitochondrial potential) and functional (phagocytosis, cytokine production) parameters tested.},

note = {2014/29},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{690,

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 = {Desligniere, Evolene 

Ehkirch, Anthony 

Botzanowski, Thomas 

Beck, Alain 

Hernandez-Alba, Oscar 

Cianferani, Sarah 

eng 

Research Support, Non-U.S. Gov't 

2020/09/05 06:00 

Anal Chem. 2020 Oct 6;92(19):12900-12908. doi: 10.1021/acs.analchem.0c01426. Epub 2020 Sep 18.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{681b,

title = {Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats},

author = {M Ibrahim and T Wasselin and E Challet and A Van Dorsselaer and Y Le Maho and T Raclot and F Bertile},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32825252},

doi = {10.3390/ijms21175984},

issn = {1422-0067 (Electronic) 1422-0067 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Int J Mol Sci},

volume = {21},

number = {17},

abstract = {Food deprivation resulting in muscle atrophy may be detrimental to health. To better understand how muscle mass is regulated during such a nutritional challenge, the current study deciphered muscle responses during phase 2 (P2, protein sparing) and phase 3 (P3, protein mobilization) of prolonged fasting in rats. This was done using transcriptomics analysis and a series of biochemistry measurements. The main findings highlight changes for plasma catabolic and anabolic stimuli, as well as for muscle transcriptome, energy metabolism, and oxidative stress. Changes were generally consistent with the intense use of lipids as fuels during P2. They also reflected increased muscle protein degradation and repressed synthesis, in a more marked manner during P3 than P2 compared to the fed state. Nevertheless, several unexpected changes appeared to be in favor of muscle protein synthesis during fasting, notably at the level of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, transcription and translation processes, and the response to oxidative stress. Such mechanisms might promote protein sparing during P2 and prepare the restoration of the protein compartment during P3 in anticipation of food intake for optimizing the effects of an upcoming refeeding, thereby promoting body maintenance and survival. Future studies should examine relevance of such targets for improving nitrogen balance during catabolic diseases.},

note = {Ibrahim, Marianne 

Wasselin, Thierry 

Challet, Etienne 

Van Dorsselaer, Alain 

Le Maho, Yvon 

Raclot, Thierry 

Bertile, Fabrice 

eng 

ANR-05-BLAN-0069/Agence Nationale de la Recherche 

ANR-10-INSB-08-03/Proteomics French Infrastructure (ProFI) 

Switzerland 

2020/08/23 06:00 

Int J Mol Sci. 2020 Aug 20;21(17). pii: ijms21175984. doi: 10.3390/ijms21175984.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{693,

title = {The catalytic activity of the translation termination factor methyltransferase Mtq2-Trm112 complex is required for large ribosomal subunit biogenesis},

author = {C Lacoux and L Wacheul and K Saraf and N Pythoud and E Huvelle and S Figaro and M Graille and C Carapito and D L J Lafontaine and V Heurgue-Hamard},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33166396},

doi = {10.1093/nar/gkaa972},

issn = {1362-4962 (Electronic) 0305-1048 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Nucleic Acids Res},

volume = {48},

number = {21},

pages = {12310-12325},

abstract = {The Mtq2-Trm112 methyltransferase modifies the eukaryotic translation termination factor eRF1 on the glutamine side chain of a universally conserved GGQ motif that is essential for release of newly synthesized peptides. Although this modification is found in the three domains of life, its exact role in eukaryotes remains unknown. As the deletion of MTQ2 leads to severe growth impairment in yeast, we have investigated its role further and tested its putative involvement in ribosome biogenesis. We found that Mtq2 is associated with nuclear 60S subunit precursors, and we demonstrate that its catalytic activity is required for nucleolar release of pre-60S and for efficient production of mature 5.8S and 25S rRNAs. Thus, we identify Mtq2 as a novel ribosome assembly factor important for large ribosomal subunit formation. We propose that Mtq2-Trm112 might modify eRF1 in the nucleus as part of a quality control mechanism aimed at proof-reading the peptidyl transferase center, where it will subsequently bind during translation termination.},

note = {Lacoux, Caroline 

Wacheul, Ludivine 

Saraf, Kritika 

Pythoud, Nicolas 

Huvelle, Emmeline 

Figaro, Sabine 

Graille, Marc 

Carapito, Christine 

Lafontaine, Denis L J 

Heurgue-Hamard, Valerie 

eng 

Research Support, Non-U.S. Gov't 

England 

2020/11/10 06:00 

Nucleic Acids Res. 2020 Dec 2;48(21):12310-12325. doi: 10.1093/nar/gkaa972.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{692,

title = {Precise Alkoxyamine Design to Enable Automated Tandem Mass Spectrometry Sequencing of Digital Poly(phosphodiester)s},

author = {K Launay and J A Amalian and E Laurent and L Oswald and A Al Ouahabi and A Burel and F Dufour and C Carapito and J L Clement and J F Lutz and L Charles and D Gigmes},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32964618},

doi = {10.1002/anie.202010171},

issn = {1521-3773 (Electronic) 1433-7851 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Angew Chem Int Ed Engl},

abstract = {A major step towards reliable reading of information coded in the sequence of long poly(phosphodiester)s was previously achieved by introducing an alkoxyamine spacer between information sub-segments. However, MS/MS decoding had to be performed manually to safely identify useful fragments of low abundance compared to side-products from the amide-based alkoxyamine used. Here, alternative alkoxyamines were designed to prevent side-reactions and enable automated MS/MS sequencing. Different styryl-TEMPO spacers were prepared to increase radical delocalization and stiffness of the structure. Their dissociation behavior was investigated by EPR and best results were obtained with spacers containing in-chain benzyl ring, with no side-reaction during synthesis or sequencing. Automated decoding of these polymers was performed using the MS-DECODER software, which interprets fragmentation data recorded for each sub-segment and re-align them in their original order based on location tags.},

note = {Launay, Kevin 

Amalian, Jean-Arthur 

Laurent, Eline 

Oswald, Laurence 

Al Ouahabi, Abdelaziz 

Burel, Alexandre 

Dufour, Florent 

Carapito, Christine 

Clement, Jean-Louis 

Lutz, Jean-Francois 

Charles, Laurence 

Gigmes, Didier 

eng 

ANR-16-CE29-0004-01/Agence Nationale de la Recherche 

ANR-16-CE29-0004-02/Agence Nationale de la Recherche 

Germany 

2020/09/24 06:00 

Angew Chem Int Ed Engl. 2020 Sep 22. doi: 10.1002/anie.202010171.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{689b,

title = {The Importance of Charge in Perturbing the Aromatic Glue Stabilizing the Protein-Protein Interface of Homodimeric tRNA-Guanine Transglycosylase},

author = {A Nguyen and D Nguyen and T X Phong Nguyen and M Sebastiani and S Dorr and O Hernandez-Alba and F Debaene and S Cianferani and A Heine and G Klebe and K Reuter},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33166460},

doi = {10.1021/acschembio.0c00700},

issn = {1554-8937 (Electronic) 1554-8929 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {ACS Chem Biol},

volume = {15},

number = {11},

pages = {3021-3029},

abstract = {Bacterial tRNA-guanine transglycosylase (Tgt) is involved in the biosynthesis of the modified tRNA nucleoside queuosine present in the anticodon wobble position of tRNAs specific for aspartate, asparagine, histidine, and tyrosine. Inactivation of the tgt gene leads to decreased pathogenicity of Shigella bacteria. Therefore, Tgt constitutes a putative target for Shigellosis drug therapy. Since it is only active as homodimer, interference with dimer-interface formation may, in addition to active-site inhibition, provide further means to disable this protein. A cluster of four aromatic residues seems important to stabilize the homodimer. We mutated residues of this aromatic cluster and analyzed each mutated variant with respect to the dimer and thermal stability or enzyme activity by applying native mass spectrometry, a thermal shift assay, enzyme kinetics, and X-ray crystallography. Our structural studies indicate a strong influence of pH on the homodimer stability. Apparently, protonation of a histidine within the aromatic cluster supports the collapse of an essential structural motif within the dimer interface at slightly acidic pH.},

note = {Nguyen, Andreas 

Nguyen, Dzung 

Phong Nguyen, Tran Xuan 

Sebastiani, Maurice 

Dorr, Stefanie 

Hernandez-Alba, Oscar 

Debaene, Francois 

Cianferani, Sarah 

Heine, Andreas 

Klebe, Gerhard 

Reuter, Klaus 

eng 

Research Support, Non-U.S. Gov't 

2020/11/10 06:00 

ACS Chem Biol. 2020 Nov 20;15(11):3021-3029. doi: 10.1021/acschembio.0c00700. Epub 2020 Nov 9.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{688,

title = {Structures of B. subtilis Maturation RNases Captured on 50S Ribosome with Pre-rRNAs},

author = {S Oerum and T Dendooven and M Catala and L Gilet and C Degut and A Trinquier and M Bourguet and P Barraud and S Cianferani and B F Luisi and C Condon and C Tisne},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32991829},

doi = {10.1016/j.molcel.2020.09.008},

issn = {1097-4164 (Electronic) 1097-2765 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Mol Cell},

volume = {80},

number = {2},

pages = {227-236 e5},

abstract = {The pathways for ribosomal RNA (rRNA) maturation diverge greatly among the domains of life. In the Gram-positive model bacterium, Bacillus subtilis, the final maturation steps of the two large ribosomal subunit (50S) rRNAs, 23S and 5S pre-rRNAs, are catalyzed by the double-strand specific ribonucleases (RNases) Mini-RNase III and RNase M5, respectively. Here we present a protocol that allowed us to solve the 3.0 and 3.1 A resolution cryoelectron microscopy structures of these RNases poised to cleave their pre-rRNA substrates within the B. subtilis 50S particle. These data provide the first structural insights into rRNA maturation in bacteria by revealing how these RNases recognize and process double-stranded pre-rRNA. Our structures further uncover how specific ribosomal proteins act as chaperones to correctly fold the pre-rRNA substrates and, for Mini-III, anchor the RNase to the ribosome. These r-proteins thereby serve a quality-control function in the process from accurate ribosome assembly to rRNA processing.},

note = {Oerum, Stephanie 

Dendooven, Tom 

Catala, Marjorie 

Gilet, Laetitia 

Degut, Clement 

Trinquier, Aude 

Bourguet, Maxime 

Barraud, Pierre 

Cianferani, Sarah 

Luisi, Ben F 

Condon, Ciaran 

Tisne, Carine 

eng 

206171/Z/17/Z/WT_/Wellcome Trust/United Kingdom 

202905/Z/16/Z/WT_/Wellcome Trust/United Kingdom 

Research Support, Non-U.S. Gov't 

2020/09/30 06:00 

Mol Cell. 2020 Oct 15;80(2):227-236.e5. doi: 10.1016/j.molcel.2020.09.008. Epub 2020 Sep 28.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{687,

title = {Structural basis for DNA recognition and allosteric control of the retinoic acid receptors RAR-RXR},

author = {J Osz and A G McEwen and M Bourguet and F Przybilla and C Peluso-Iltis and P Poussin-Courmontagne and Y Mely and S Cianferani and C M Jeffries and D I Svergun and N Rochel},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32974652},

doi = {10.1093/nar/gkaa697},

issn = {1362-4962 (Electronic) 0305-1048 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Nucleic Acids Res},

volume = {48},

number = {17},

pages = {9969-9985},

abstract = {Retinoic acid receptors (RARs) as a functional heterodimer with retinoid X receptors (RXRs), bind a diverse series of RA-response elements (RAREs) in regulated genes. Among them, the non-canonical DR0 elements are bound by RXR-RAR with comparable affinities to DR5 elements but DR0 elements do not act transcriptionally as independent RAREs. In this work, we present structural insights for the recognition of DR5 and DR0 elements by RXR-RAR heterodimer using x-ray crystallography, small angle x-ray scattering, and hydrogen/deuterium exchange coupled to mass spectrometry. We solved the crystal structures of RXR-RAR DNA-binding domain in complex with the Rarb2 DR5 and RXR-RXR DNA-binding domain in complex with Hoxb13 DR0. While cooperative binding was observed on DR5, the two molecules bound non-cooperatively on DR0 on opposite sides of the DNA. In addition, our data unveil the structural organization and dynamics of the multi-domain RXR-RAR DNA complexes providing evidence for DNA-dependent allosteric communication between domains. Differential binding modes between DR0 and DR5 were observed leading to differences in conformation and structural dynamics of the multi-domain RXR-RAR DNA complexes. These results reveal that the topological organization of the RAR binding element confer regulatory information by modulating the overall topology and structural dynamics of the RXR-RAR heterodimers.},

note = {Osz, Judit 

McEwen, Alastair G 

Bourguet, Maxime 

Przybilla, Frederic 

Peluso-Iltis, Carole 

Poussin-Courmontagne, Pierre 

Mely, Yves 

Cianferani, Sarah 

Jeffries, Cy M 

Svergun, Dmitri I 

Rochel, Natacha 

eng 

Research Support, Non-U.S. Gov't 

England 

2020/09/26 06:00 

Nucleic Acids Res. 2020 Sep 25;48(17):9969-9985. doi: 10.1093/nar/gkaa697.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{683b,

title = {Proteomic as an Exploratory Approach to Develop Vaccines Against Tick-Borne Diseases Using Lyme Borreliosis as a Test Case},

author = {E Talagrand-Reboul and B Westermann and M A Raess and G Schnell and P Cantero and C Barthel and L Ehret-Sabatier and B Jaulhac and N Boulanger},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32825641},

doi = {10.3390/vaccines8030463},

issn = {2076-393X (Print) 2076-393X (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Vaccines (Basel)},

volume = {8},

number = {3},

abstract = {Tick-borne diseases affecting humans and animals are on the rise worldwide. Vaccines constitute an effective control measure, but very few are available. We selected Lyme borreliosis, a bacterial infection transmitted by the hard tick Ixodes, to validate a new concept to identify vaccine candidates. This disease is the most common tick-borne disease in the Northern Hemisphere. Although attempts to develop a vaccine exist, none have been successfully marketed. In tick-borne diseases, the skin constitutes a very specific environment encountered by the pathogen during its co-inoculation with tick saliva. In a mouse model, we developed a proteomic approach to identify vaccine candidates in skin biopsies. We identified 30 bacterial proteins after syringe inoculation or tick inoculation of bacteria. Discovery proteomics using mass spectrometry might be used in various tick-borne diseases to identify pathogen proteins with early skin expression. It should help to better develop sub-unit vaccines based on a cocktail of several antigens, associated with effective adjuvant and delivery systems of antigens. In all vector-borne diseases, the skin deserves further investigation to better define its role in the elaboration of protective immunity against pathogens.},

note = {2012-31},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{685,

title = {How Reversible Are the Effects of Fumed Silica on Macrophages? A Proteomics-Informed View},

author = {A Torres and B Dalzon and V Collin-Faure and H Diemer and D Fenel and G Schoehn and S Cianferani and M Carriere and T Rabilloud},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33003391},

doi = {10.3390/nano10101939},

issn = {2079-4991 (Print) 2079-4991 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Nanomaterials (Basel)},

volume = {10},

number = {10},

abstract = {Synthetic amorphous silica is one of the most used nanomaterials, and numerous toxicological studies have studied its effects. Most of these studies have used an acute exposure mode to investigate the effects immediately after exposure. However, this exposure modality does not allow the investigation of the persistence of the effects, which is a crucial aspect of silica toxicology, as exemplified by crystalline silica. In this paper, we extended the investigations by studying not only the responses immediately after exposure but also after a 72 h post-exposure recovery phase. We used a pyrolytic silica as the test nanomaterial, as this variant of synthetic amorphous silica has been shown to induce a more persistent inflammation in vivo than precipitated silica. To investigate macrophage responses to pyrolytic silica, we used a combination of proteomics and targeted experiments, which allowed us to show that most of the cellular functions that were altered immediately after exposure to pyrolytic silica at a subtoxic dose, such as energy metabolism and cell morphology, returned to normal at the end of the recovery period. However, some alterations, such as the inflammatory responses and some aldehyde detoxification proteins, were persistent. At the proteomic level, other alterations, such as proteins implicated in the endosomal/lysosomal pathway, were also persistent but resulted in normal function, thus suggesting cellular adaptation.},

note = {Torres, Anaelle 

Dalzon, Bastien 

Collin-Faure, Veronique 

Diemer, Helene 

Fenel, Daphna 

Schoehn, Guy 

Cianferani, Sarah 

Carriere, Marie 

Rabilloud, Thierry 

eng 

PNREST 2015/032/Agence Nationale de Securite Sanitaire de l'Alimentation, de l'Environnement et du Travail 

ANR-16-CE34-0011; ANR-11-LABX-0064; ANR-10-INBS-05-02; ANR-17-EURE-0003; ANR-10-INBS-08-03/Agence Nationale de la Recherche 

Switzerland 

2020/10/03 06:00 

Nanomaterials (Basel). 2020 Sep 29;10(10). pii: nano10101939. doi: 10.3390/nano10101939.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lesne2020,

title = {Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks.},

author = {Jean Lesne and Marie Locard-Paulet and Julien Parra and Dušan Zivković and Thomas Menneteau and Marie-Pierre Bousquet and Odile Burlet-Schiltz and Julien Marcoux},

year  = {2020},

date = {2020-01-01},

journal = {Nature communications},

volume = {11},

number = {1},

pages = {6140},

abstract = {Hydrogen-Deuterium eXchange coupled to Mass Spectrometry (HDX-MS) is now common practice in structural biology. However, it is most of the time applied to rather small oligomeric complexes. Here, we report on the use of HDX-MS to investigate conformational differences between the human standard 20S (std20S) and immuno 20S (i20s) proteasomes alone or in complex with PA28$alpha$$beta$ or PA28$gamma$ activators. Their solvent accessibility is analyzed through a dedicated bioinformatic pipeline including stringent statistical analysis and 3D visualization. These data confirm the existence of allosteric differences between the std20S and i20S at the surface of the $alpha$-ring triggered from inside the catalytic $beta$-ring. Additionally, binding of the PA28 regulators to the 20S proteasomes modify solvent accessibility due to conformational changes of the $beta$-rings. This work is not only a proof-of-concept that HDX-MS can be used to get structural insights on large multi-protein complexes in solution, it also demonstrates that the binding of the std20S or i20S subtype to any of its PA28 activator triggers allosteric changes that are specific to this 20S/PA28 pair.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sorroche2020,

title = {The ex planta signal activity of a Medicago ribosomal uL2 protein suggests a moonlighting role in controlling secondary rhizobial infection.},

author = {Fernando Sorroche and Violette Morales and Saïda Mouffok and Carole Pichereaux and Marie A Garnerone and Lan Zou and Badrish Soni and Marie-Anne Carpéné and Audrey Gargaros and Fabienne Maillet and Odile Burlet-Schiltz and Verena Poinsot and Patrice Polard and Clare Gough and Jacques Batut},

year  = {2020},

date = {2020-01-01},

journal = {PloS one},

volume = {15},

number = {10},

pages = {e0235446},

abstract = {We recently described a regulatory loop, which we termed autoregulation of infection (AOI), by which Sinorhizobium meliloti, a Medicago endosymbiont, downregulates the root susceptibility to secondary infection events via ethylene. AOI is initially triggered by so-far unidentified Medicago nodule signals named signal 1 and signal 1' whose transduction in bacteroids requires the S. meliloti outer-membrane-associated NsrA receptor protein and the cognate inner-membrane-associated adenylate cyclases, CyaK and CyaD1/D2, respectively. Here, we report on advances in signal 1 identification. Signal 1 activity is widespread as we robustly detected it in Medicago nodule extracts as well as in yeast and bacteria cell extracts. Biochemical analyses indicated a peptidic nature for signal 1 and, together with proteomic analyses, a universally conserved Medicago ribosomal protein of the uL2 family was identified as a candidate signal 1. Specifically, MtRPuL2A (MtrunA17Chr7g0247311) displays a strong signal activity that requires S. meliloti NsrA and CyaK, as endogenous signal 1. We have shown that MtRPuL2A is active in signaling only in a non-ribosomal form. A Medicago truncatula mutant in the major symbiotic transcriptional regulator MtNF-YA1 lacked most signal 1 activity, suggesting that signal 1 is under developmental control. Altogether, our results point to the MtRPuL2A ribosomal protein as the candidate for signal 1. Based on the Mtnf-ya1 mutant, we suggest a link between root infectiveness and nodule development. We discuss our findings in the context of ribosomal protein moonlighting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{LeMoigne2020,

title = {A TLR2-Activating Fraction From Mycobacterium abscessus Rough Variant Demonstrates Vaccine and Diagnostic Potential.},

author = {Vincent Le Moigne and Anne-Laure Roux and Aude Jobart-Malfait and Landry Blanc and Karima Chaoui and Odile Burlet-Schiltz and Jean-Louis Gaillard and Stéphane Canaan and Jérôme Nigou and Jean-Louis Herrmann},

year  = {2020},

date = {2020-01-01},

journal = {Frontiers in cellular and infection microbiology},

volume = {10},

pages = {432},

abstract = {Mycobacterium abscessus is a prevalent pathogenic mycobacterium in cystic fibrosis (CF) patients and one of the most highly drug resistant mycobacterial species to antimicrobial agents. It possesses the property to transition from a smooth (S) to a rough (R) morphotype, thereby influencing the host innate immune response. This transition from the S to the R morphotype takes place in patients with an exacerbation of the disease and a persistence of M. abscessus. We have previously shown that the exacerbation of the Toll-like receptor 2 (TLR2)-mediated inflammatory response, following this S to R transition, is essentially due to overproduction of bacilli cell envelope surface compounds, which we were able to extract by mechanical treatment and isolation by solvent partition in a fraction called interphase. Here, we set up a purification procedure guided by bioactivity to isolate a fraction from the R variant of M. abscessus cells which exhibits a high TLR2 stimulating activity, referred to as TLR2-enriched fraction (TLR2eF). As expected, TLR2eF was found to contain several lipoproteins and proteins known to be stimuli for TLR2. Vaccination with TLR2eF showed no protection toward an M. abscessus aerosol challenge, but provided mild protection in $Delta$F508 mice and their FVB littermates when intravenously challenged by M. abscessus. Interestingly however, antibodies against TLR2eF compounds were detected during disease in CF patients. In conclusion, we show the potential for compounds in TLR2eF as vaccine and diagnostic candidates, in order to enhance diagnosis, prevent and/or treat M. abscessus-related infections.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Locard-Paulet2020,

title = {LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions.},

author = {Marie Locard-Paulet and Guillaume Voisinne and Carine Froment and Marisa Goncalves Menoita and Youcef Ounoughene and Laura Girard and Claude Gregoire and Daiki Mori and Manuel Martinez and Hervé Luche and Jerôme Garin and Marie Malissen and Odile Burlet-Schiltz and Bernard Malissen and Anne Peredo and Romain Roncagalli},

year  = {2020},

date = {2020-01-01},

journal = {Molecular systems biology},

volume = {16},

number = {7},

pages = {e9524},

abstract = {T-cell receptor (TCR) ligation-mediated protein phosphorylation regulates the activation, cellular responses, and fates of T cells. Here, we used time-resolved high-resolution phosphoproteomics to identify, quantify, and characterize the phosphorylation dynamics of thousands of phosphorylation sites in primary T cells during the first 10 min after TCR stimulation. Bioinformatic analysis of the data revealed a coherent orchestration of biological processes underlying T-cell activation. In particular, functional modules associated with cytoskeletal remodeling, transcription, translation, and metabolic processes were mobilized within seconds after TCR engagement. Among proteins whose phosphorylation was regulated by TCR stimulation, we demonstrated, using a fast-track gene inactivation approach in primary lymphocytes, that the ITSN2 adaptor protein regulated T-cell effector functions. This resource, called LymphoAtlas, represents an integrated pipeline to further decipher the organization of the signaling network encoding T-cell activation. LymphoAtlas is accessible to the community at: https://bmm-lab.github.io/LymphoAtlas.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Thouvenel2020,

title = {The final assembly of trehalose polyphleates takes place within the outer layer of the mycobacterial cell envelope.},

author = {Laurie Thouvenel and Gautier Prevot and Laura Chiaradia and Julien Parra and Emmanuelle Mouton-Barbosa and Marie Locard-Paulet and Julien Marcoux and Maryelle Tropis and Odile Burlet-Schiltz and Mamadou Daffé and Christophe Guilhot and Gilles Etienne and Christian Chalut},

year  = {2020},

date = {2020-01-01},

journal = {The Journal of biological chemistry},

volume = {295},

number = {32},

pages = {11184--11194},

abstract = {Trehalose polyphleates (TPP) are high-molecular-weight, surface-exposed glycolipids present in a broad range of nontuberculous mycobacteria. These compounds consist of a trehalose core bearing polyunsaturated fatty acyl substituents (called phleic acids) and a straight-chain fatty acid residue and share a common basic structure with trehalose-based glycolipids produced by Mycobacterium tuberculosis TPP production starts in the cytosol with the formation of a diacyltrehalose intermediate. An acyltransferase, called PE, subsequently catalyzes the transfer of phleic acids onto diacyltrehalose to form TPP, and an MmpL transporter promotes the export of TPP or its precursor across the plasma membrane. PE is predicted to be an anchored membrane protein, but its topological organization is unknown, raising questions about the subcellular localization of the final stage of TPP biosynthesis and the chemical nature of the substrates that are translocated by the MmpL transporter. Here, using genetic, biochemical, and proteomic approaches, we established that PE of Mycobacterium smegmatis is exported to the cell envelope following cleavage of its signal peptide and that this process is required for TPP biosynthesis, indicating that the last step of TPP formation occurs in the outer layers of the mycobacterial cell envelope. These results provide detailed insights into the molecular mechanisms controlling TPP formation and transport to the cell surface, enabling us to propose an updated model of the TPP biosynthetic pathway. Because the molecular mechanisms of glycolipid production are conserved among mycobacteria, these findings obtained with PE from M. smegmatis may offer clues to glycolipid formation in M. tuberculosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Le2020,

title = {The protein kinase PknB negatively regulates biosynthesis and trafficking of mycolic acids in mycobacteria.},

author = {Nguyen-Hung Le and Marie Locard-Paulet and Alexandre Stella and Nicolas Tomas and Virginie Molle and Odile Burlet-Schiltz and Mamadou Daffé and Hedia Marrakchi},

year  = {2020},

date = {2020-01-01},

journal = {Journal of lipid research},

volume = {61},

number = {8},

pages = {1180--1191},

abstract = {Mycobacterium tuberculosis is the causative agent of tuberculosis and remains one of the most widespread and deadliest bacterial pathogens in the world. A distinguishing feature of mycobacteria that sets them apart from other bacteria is the unique architecture of their cell wall, characterized by various species-specific lipids, most notably mycolic acids (MAs). Therefore, targeted inhibition of enzymes involved in MA biosynthesis, transport, and assembly has been extensively explored in drug discovery. Additionally, more recent evidence suggests that many enzymes in the MA biosynthesis pathway are regulated by kinase-mediated phosphorylation, thus opening additional drug-development opportunities. However, how phosphorylation regulates MA production remains unclear. Here, we used genetic strategies combined with lipidomics and phosphoproteomics approaches to investigate the role of protein phosphorylation in Mycobacterium The results of this analysis revealed that the Ser/Thr protein kinase PknB regulates the export of MAs and promotes the remodeling of the mycobacterial cell envelope. In particular, we identified the essential MmpL3 as a substrate negatively regulated by PknB. Taken together, our findings add to the understanding of how PknB activity affects the mycobacterial MA biosynthesis pathway and reveal the essential role of protein phosphorylation/dephosphorylation in governing lipid metabolism, paving the way for novel antimycobacterial strategies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Soler2020,

title = {Proteome changes induced by a short, non-cytotoxic exposure to the mycoestrogen zearalenone in the pig intestine.},

author = {Laura Soler and Alexandre Stella and Juan Seva and Francisco Jose Pallarés and Tarek Lahjouji and Odile Burlet-Schiltz and Isabelle P Oswald},

year  = {2020},

date = {2020-01-01},

journal = {Journal of proteomics},

volume = {224},

pages = {103842},

address = {Netherlands},

abstract = {Intestinal epithelial homeostasis is regulated by a complex network of signaling pathways. Among them is estrogen signaling, important for the proliferation and differentiation of epithelial cells, immune signaling and metabolism. The mycotoxin zearalenone (ZEN) is an estrogen disruptor naturally found in food and feed. The exposure of the intestine to ZEN has toxic effects including alteration of the immune status and is possibly implicated in carcinogenesis, but the molecular mechanisms linked with these effects are not clear. Our objective was to explore the proteome changes induced by a short, non-cytotoxic exposure to ZEN in the intestine using pig jejunal explants. Our results indicated that ZEN promotes little proteome changes, but significantly related with an induction of ER$alpha$ signaling and a consequent disruption of highly interrelated signaling cascades, such as NF-$kappa$B, ERK1/2, CDX2 and HIF1$alpha$. The toxicity of ZEN leads also to an altered immune status characterized by the activation of the chemokine CXCR4/SDF-1 axis and an accumulation of MHC-I proteins. Our results connect the estrogen disrupting activity of ZEN with its intestinal toxic effect, associating the exposure to ZEN with cell-signaling disorders similar to those involved in the onset and progression of diseases such as cancer and chronic inflammatory disorders. SIGNIFICANCE: The proteomics results presented in our study indicate that the endocrine disruptor activity of ZEN is able to regulate a cascade of highly inter-connected signaling events essential for the small intestinal crypt-villus cycle and immune status. These molecular mechanisms are also implicated in the onset and progress of intestinal immune disorders and cancer indicating that exposure to ZEN could play an important role in intestinal pathogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Blaize2020,

title = {CD5 signalosome coordinates antagonist TCR signals to control the generation of Treg cells induced by foreign antigens.},

author = {Gaëtan Blaize and Hélène Daniels-Treffandier and Meryem Aloulou and Nelly Rouquié and Cui Yang and Marlène Marcellin and Mylène Gador and Mehdi Benamar and Mariette Ducatez and Ki-Duk Song and Odile Burlet-Schiltz and Abdelhadi Saoudi and Paul E Love and Nicolas Fazilleau and Anne Peredo and Renaud Lesourne},

year  = {2020},

date = {2020-01-01},

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

volume = {117},

number = {23},

pages = {12969--12979},

abstract = {CD5 is characterized as an inhibitory coreceptor with an important regulatory role during T cell development. The molecular mechanism by which CD5 operates has been puzzling and its function in mature T cells suggests promoting rather than repressing effects on immune responses. Here, we combined quantitative mass spectrometry and genetic studies to analyze the components and the activity of the CD5 signaling machinery in primary T cells. We found that T cell receptor (TCR) engagement induces the selective phosphorylation of CD5 tyrosine 429, which serves as a docking site for proteins with adaptor functions (c-Cbl, CIN85, CRKL), connecting CD5 to positive (PI3K) and negative (UBASH3A, SHIP1) regulators of TCR signaling. c-CBL acts as a coordinator in this complex enabling CD5 to synchronize positive and negative feedbacks on TCR signaling through the other components. Disruption of CD5 signalosome in mutant mice reveals that it modulates TCR signal outputs to selectively repress the transactivation of Foxp3 and limit the inopportune induction of peripherally induced regulatory T cells during immune responses against foreign antigen. Our findings bring insights into the paradigm of coreceptor signaling, suggesting that, in addition to providing dualistic enhancing or dampening inputs, coreceptors can engage concomitant stimulatory and inhibitory signaling events, which act together to promote specific functional outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bouyssie2020,

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

author = {David Bouyssié and Anne-Marie Hesse and Emmanuelle Mouton-Barbosa and Magali Rompais and Charlotte Macron and Christine Carapito and Anne Peredo and Yohann Couté and Véronique Dupierris and Alexandre Burel and Jean-Philippe Menetrey and Andrea Kalaitzakis and Julie Poisat and Aymen Romdhani and Odile Burlet-Schiltz and Sarah Cianférani and Jerome Garin and Christophe Bruley},

year  = {2020},

date = {2020-01-01},

journal = {Bioinformatics (Oxford, England)},

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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pechalrieu2020,

title = {Bisubstrate-Type Chemical Probes Identify GRP94 as a Potential Target of Cytosine-Containing Adenosine Analogs.},

author = {Dany Pechalrieu and Fanny Assemat and Ludovic Halby and Marlene Marcellin and Pengrong Yan and Karima Chaoui and Sahil Sharma and Gabriela Chiosis and Odile Burlet-Schiltz and Paola B Arimondo and Marie Lopez},

year  = {2020},

date = {2020-01-01},

journal = {ACS chemical biology},

volume = {15},

number = {4},

pages = {952--961},

abstract = {We synthesized affinity-based chemical probes of cytosine-adenosine bisubstrate analogs and identified several potential targets by proteomic analysis. The validation of the proteomic analysis identified the chemical probe as a specific inhibitor of glucose-regulated protein 94 (GRP94), a potential drug target for several types of cancers. Therefore, as a result of the use of bisubstrate-type chemical probes and a chemical-biology methodology, this work opens the way to the development of a new family of GRP94 inhibitors that could potentially be of therapeutic interest.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Imbert2020,

title = {Resistance of melanoma to immune checkpoint inhibitors is overcome by targeting the sphingosine kinase-1.},

author = {Caroline Imbert and Anne Montfort and Marine Fraisse and Elie Marcheteau and Julia Gilhodes and Elodie Martin and Florie Bertrand and Marlène Marcellin and Odile Burlet-Schiltz and Anne Gonzalez Peredo and Virginie Garcia and Stéphane Carpentier and Sophie Tartare-Deckert and Pierre Brousset and Philippe Rochaix and Florent Puisset and Thomas Filleron and Nicolas Meyer and Laurence Lamant and Thierry Levade and Bruno Ségui and Nathalie Andrieu-Abadie and Céline Colacios},

year  = {2020},

date = {2020-01-01},

journal = {Nature communications},

volume = {11},

number = {1},

pages = {437},

abstract = {Immune checkpoint inhibitors (ICIs) have dramatically modified the prognosis of several advanced cancers, however many patients still do not respond to treatment. Optimal results might be obtained by targeting cancer cell metabolism to modulate the immunosuppressive tumor microenvironment. Here, we identify sphingosine kinase-1 (SK1) as a key regulator of anti-tumor immunity. Increased expression of SK1 in tumor cells is significantly associated with shorter survival in metastatic melanoma patients treated with anti-PD-1. Targeting SK1 markedly enhances the responses to ICI in murine models of melanoma, breast and colon cancer. Mechanistically, SK1 silencing decreases the expression of various immunosuppressive factors in the tumor microenvironment to limit regulatory T cell (Treg) infiltration. Accordingly, a SK1-dependent immunosuppressive signature is also observed in human melanoma biopsies. Altogether, this study identifies SK1 as a checkpoint lipid kinase that could be targeted to enhance immunotherapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Clement2020,

title = {Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells.},

author = {Emily Clement and Ikrame Lazar and Camille Attané and Lorry Carrié and Stéphanie Dauvillier and Manuelle Ducoux-Petit and David Esteve and Thomas Menneteau and Mohamed Moutahir and Sophie Le Gonidec and Stéphane Dalle and Philippe Valet and Odile Burlet-Schiltz and Catherine Muller and Laurence Nieto},

year  = {2020},

date = {2020-01-01},

journal = {The EMBO journal},

volume = {39},

number = {3},

pages = {e102525},

abstract = {Extracellular vesicles are emerging key actors in adipocyte communication. Notably, small extracellular vesicles shed by adipocytes stimulate fatty acid oxidation and migration in melanoma cells and these effects are enhanced in obesity. However, the vesicular actors and cellular processes involved remain largely unknown. Here, we elucidate the mechanisms linking adipocyte extracellular vesicles to metabolic remodeling and cell migration. We show that adipocyte vesicles stimulate melanoma fatty acid oxidation by providing both enzymes and substrates. In obesity, the heightened effect of extracellular vesicles depends on increased transport of fatty acids, not fatty acid oxidation-related enzymes. These fatty acids, stored within lipid droplets in cancer cells, drive fatty acid oxidation upon being released by lipophagy. This increase in mitochondrial activity redistributes mitochondria to membrane protrusions of migrating cells, which is necessary to increase cell migration in the presence of adipocyte vesicles. Our results provide key insights into the role of extracellular vesicles in the metabolic cooperation that takes place between adipocytes and tumors with particular relevance to obesity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pirro2020,

title = {Characterization of Macrophage Galactose-type Lectin (MGL) ligands in colorectal cancer cell lines.},

author = {Martina Pirro and Yoann Rombouts and Alexandre Stella and Olivier Neyrolles and Odile Burlet-Schiltz and Sandra J Vliet and Arnoud H Ru and Yassene Mohammed and Manfred Wuhrer and Peter A Veelen and Paul J Hensbergen},

year  = {2020},

date = {2020-01-01},

journal = {Biochimica et biophysica acta. General subjects},

volume = {1864},

number = {4},

pages = {129513},

address = {Netherlands},

abstract = {BACKGROUND: The Ca(2+)-dependent C-type lectin receptor Macrophage Galactose-type Lectin (MGL) is highly expressed by tolerogenic dendritic cells (DC) and macrophages. MGL exhibits a high binding specificity for terminal alpha- and beta-linked GalNAc residues found in Tn, sTn and LacdiNAc antigens. These glycan epitopes are often overexpressed in colorectal cancer (CRC), and, as such, MGL can be used to discriminate tumor from the corresponding healthy tissues. Moreover, the high expression of MGL ligands is associated with poor disease-free survival in stage III of CRC tumors. Nonetheless, the glycoproteins expressed by tumor cells that are recognized by MGL have hitherto remained elusive. METHODS: Using a panel of three CRC cell lines (HCT116, HT29 and LS174T), recapitulating CRC diversity, we performed FACS staining and pull-down assays using a recombinant soluble form of MGL (and a mutant MGL as control) combined with mass spectrometry-based (glyco)proteomics. RESULTS: HCT116 and HT29, but not LS174T, are high MGL-binding CRC cell lines. On these cells, the major cell surface binding proteins are receptors (e.g. MET, PTK7, SORL1, PTPRF) and integrins (ITGB1, ITGA3). From these proteins, several N- and/or O-glycopeptides were identified, of which some carried either a LacdiNAc or Tn epitope. CONCLUSIONS: We have identified cell surface MGL-ligands on CRC cell lines. GENERAL SIGNIFICANCE: Advances in (glyco)proteomics have led to identification of candidate key mediators of immune-evasion and tumor growth in CRC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1401,

title = {Drug Loading and Distribution of ADCs After Reduction or IdeS Digestion and Reduction},

author = {E. Wagner-Rousset and O. Colas and Y. N. Francois and S. Heinisch and D. Guillarme and S. Cianferani and A. Beck},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31643057},

doi = {10.1007/978-1-4939-9929-3_12},

issn = {1940-6029 (Electronic) 

1064-3745 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Methods Mol Biol},

volume = {2078},

pages = {187-195},

abstract = {High-resolution native mass spectrometry (MS) provides accurate mass measurements (within 30 ppm) of intact ADCs and can also yield drug load distribution (DLD) and average drug to antibody ratio (DAR) in parallel with hydrophobic interaction chromatography (HIC). Native MS is furthermore unique in its ability to simultaneously detect covalent and noncovalent species in a mixture and for HIC peak identity assessment offline or online.As an orthogonal method described in this chapter, LC-MS following ADC reduction or IdeS (Fabricator) digestion and reduction can also be used to measure the DLD of light chain and Fd fragments for hinge native cysteine residues such as brentuximab vedotin. Both methods allow also the measurement of average DAR for both monomeric and multimeric species. In addition, the Fc fragments can be analyzed in the same run, providing a complete glycoprofile and the demonstration or absence of additional conjugation of this subdomain involved in FcRn and Fc-gammaR binding.},

note = {pas de manip MS LSMBO},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1393,

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},

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.},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1395,

title = {Determination of size variants by CE-SDS for approved therapeutic antibodies: Key implications of subclasses and light chain specificities},

author = {E. Wagner and O. Colas and S. Chenu and A. Goyon and A. Murisier and S. Cianferani and Y. Francois and S. Fekete and D. Guillarme and V. D'Atri and A. Beck},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32113118},

doi = {10.1016/j.jpba.2020.113166},

issn = {1873-264X (Electronic) 

0731-7085 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {J Pharm Biomed Anal},

volume = {184},

pages = {113166},

abstract = {In the present work, a generic non-reducing capillary electrophoresis sodium dodecyl sulphate (nrCE-SDS) method was tested for a wide range of 26 FDA and EMA approved monoclonal antibodies (mAbs) and 2 antibody drug conjugates (ADCs) as well as for the NISTmab, in a QC environment (e.g. testing quality requirements for batch manufacturing or batch release). This method allows obtaining rapidly and accurately the amount of size variants in drug products within about 40min and may be used for batch release and consistency as well as for stability and shelf-life. First, the method repeatability was found to be excellent in terms of relative migration times and relative proportions of fragments (average RSD values of 0.3 and 0.2 %, on relative migration times and relative percentages of fragments, respectively), thanks to the addition of an internal standard. A panel of chimeric, humanized and human mAbs were tested, belonging to different subclasses (heavy chain gamma 1, 2, 2/4 and 4) and light chain types (kappa or lambda) and produced in different cell lines (CHO, NS0 and SP2/0). For all these biopharmaceutical products, the amount of H2L2 species was comprised between 90.9 % and 97.7 %, except for the two mAbs belonging to the IgG1lambda subclass, namely avelumab and belimumab, which were prone to partial reduction during the sample preparation at 70 degrees C. Based on the CE-SDS results obtained for a diverse panel of therapeutic antibodies investigated in this study, and covering a wide range of structural and physico-chemical properties, a specification on the intact antibody content (H2L2) greater than 90 % can be achieved.},

note = {pas de manip MS},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1824,

title = {Inhibition of mitophagy drives macrophage activation and antibacterial defense during sepsis},

author = {D. Patoli and F. Mignotte and V. Deckert and A. Dusuel and A. Dumont and A. Rieu and A. Jalil and K. Van Dongen and T. Bourgeois and T. Gautier and C. Magnani and N. Le Guern and S. Mandard and J. Bastin and F. Djouadi and C. Schaeffer and N. Guillaumot and M. Narce and M. Nguyen and J. Guy and A. Dargent and J. P. Quenot and M. Rialland and D. Masson and J. Auwerx and L. Lagrost and C. Thomas},

url = {<Go to ISI>://WOS:000587413700026},

doi = {10.1172/Jci130996},

issn = {0021-9738},

year  = {2020},

date = {2020-01-01},

journal = {Journal of Clinical Investigation},

volume = {130},

number = {11},

pages = {5858-5874},

abstract = {Mitochondria have emerged as key actors of innate and adaptive immunity. Mitophagy has a pivotal role in cell homeostasis, but its contribution to macrophage functions and host defense remains to be delineated. Here, we showed that lipopolysaccharide (LPS) in combination with IFN-gamma inhibited PINK1-dependent mitophagy in macrophages through a STAT1-dependent activation of the inflammatory caspases 1 and 11. In addition, we demonstrated that the inhibition of mitophagy triggered classical macrophage activation in a mitochondrial ROS-dependent manner. In a murine model of polymicrobial infection (cecal ligature and puncture), adoptive transfer of Pink1-deficient bone marrow or pharmacological inhibition of mitophagy promoted macrophage activation, which favored bactericidal clearance and led to a better survival rate. Reciprocally, mitochondrial uncouplers that promote mitophagy reversed LPS/IFN-gamma-mediated activation of macrophages and led to immunoparalysis with impaired bacterial clearance and lowered survival. In critically ill patients, we showed that mitophagy was inhibited in blood monocytes of patients with sepsis as compared with nonseptic patients. Overall, this work demonstrates that the inhibition of mitophagy is a physiological mechanism that contributes to the activation of myeloid cells and improves the outcome of sepsis.},

note = {???},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1823,

title = {Human proteinase 3 resistance to inhibition extends to alpha-2 macroglobulin},

author = {K. N'Guessan and R. Grzywa and S. Seren and G. Gabant and M. A. Juliano and M. Moniatte and A. Dorsselaer and J. G. Bieth and C. Kellenberger and F. Gauthier and M. Wysocka and A. Lesner and M. Sienczyk and M. Cadene and B. Korkmaz},

url = {<Go to ISI>://WOS:000515330900001},

doi = {10.1111/febs.15229},

issn = {1742-464x},

year  = {2020},

date = {2020-01-01},

journal = {Febs Journal},

volume = {287},

number = {18},

pages = {4068-4081},

abstract = {Polymorphonuclear neutrophils contain at least four serine endopeptidases, namely neutrophil elastase (NE), proteinase 3 (PR3), cathepsin G (CatG), and NSP4, which contribute to the regulation of infection and of inflammatory processes. In physiological conditions, endogenous inhibitors including alpha 2-macroglobulin (alpha 2-M), serpins [alpha 1-proteinase inhibitor (alpha 1-PI)], monocyte neutrophil elastase inhibitor (MNEI), alpha 1-antichymotrypsin, and locally produced chelonianins (elafin, SLPI) control excessive proteolytic activity of neutrophilic serine proteinases. In contrast to human NE (hNE), hPR3 is weakly inhibited by alpha 1-PI and MNEI but not by SLPI. alpha 2-M is a large spectrum inhibitor that traps a variety of proteinases in response to cleavage(s) in its bait region. We report here that alpha 2-M was more rapidly processed by hNE than hPR3 or hCatG. This was confirmed by the observation that the association between alpha 2-M and hPR3 is governed by a k(ass) in the <= 10(5) m(-1)center dot s(-1) range. Since alpha 2-M-trapped proteinases retain peptidase activity, we first predicted the putative cleavage sites within the alpha 2-M bait region (residues 690-728) using kinetic and molecular modeling approaches. We then identified by mass spectrum analysis the cleavage sites of hPR3 in a synthetic peptide spanning the 39-residue bait region of alpha 2-M (39pep-alpha 2-M). Since the 39pep-alpha 2-M peptide and the corresponding bait area in the whole protein do not contain sequences with a high probability of specific cleavage by hPR3 and were indeed only slowly cleaved by hPR3, it can be concluded that alpha 2-M is a poor inhibitor of hPR3. The resistance of hPR3 to inhibition by endogenous inhibitors explains at least in part its role in tissue injury during chronic inflammatory diseases and its well-recognized function of major target autoantigen in granulomatosis with polyangiitis.},

note = {Pas de projet},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1504,

title = {Tenascin-C Orchestrates an Immune-Suppressive Tumor Microenvironment in Oral Squamous Cell Carcinoma},

author = {C. Spenle and T. Loustau and D. Murdamoothoo and W. Erne and S. Beghelli-de la Forest Divonne and R. Veber and L. Petti and P. Bourdely and M. Morgelin and E. M. Brauchle and G. Cremel and V. Randrianarisoa and A. Camara and S. Rekima and S. Schaub and K. Nouhen and T. Imhof and U. Hansen and N. Paul and R. Carapito and N. Pythoud and A. Hirschler and C. Carapito and H. Dumortier and C. G. Mueller and M. Koch and K. Schenke-Layland and S. Kon and A. Sudaka and F. Anjuere and E. Van Obberghen-Schilling and G. Orend},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32665262},

doi = {10.1158/2326-6066.CIR-20-0074},

issn = {2326-6074 (Electronic) 

2326-6066 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Cancer Immunol Res},

abstract = {Inherent immune suppression represents a major challenge in the treatment of human cancer. The extracellular matrix molecule tenascin-C promotes cancer by multiple mechanisms, yet the roles of tenascin-C in tumor immunity are incompletely understood. Using a 4NQO-induced oral squamous cell carcinoma (OSCC) model with abundant and absent tenascin-C, we demonstrated that tenascin-C enforced an immune-suppressive lymphoid stroma via CCL21/CCR7 signaling, leading to increased metastatic tumors. Through TLR4, tenascin-C increased expression of CCR7 in CD11c(+) myeloid cells. By inducing CCL21 in lymphatic endothelial cells via integrin alpha9beta1 and binding to CCL21, tenascin-C immobilized CD11c(+) cells in the stroma. Inversion of the lymph node-to-tumor CCL21 gradient, recruitment of T regulatory cells, high expression of anti-inflammatory cytokines, and matrisomal components were hallmarks of the tenascin-C-instructed lymphoid stroma. Ablation of tenascin-C or CCR7 blockade inhibited the lymphoid immune-suppressive stromal properties, reducing tumor growth, progression, and metastasis. Thus, targeting CCR7 could be relevant in human head and neck tumors, as high tenascin-C expression and an immune-suppressive stroma correlate to poor patient survival.},

note = {2019/08},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1394,

title = {Ethynylation of Cysteine Residues: From Peptides to Proteins in Vitro and in Living Cells},

author = {R. Tessier and R. K. Nandi and B. G. Dwyer and D. Abegg and C. Sornay and J. Ceballos and S. Erb and S. Cianferani and A. Wagner and G. Chaubet and A. Adibekian and J. Waser},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32233093},

doi = {10.1002/anie.202002626},

issn = {1521-3773 (Electronic) 

1433-7851 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Angew Chem Int Ed Engl},

volume = {59},

number = {27},

pages = {10961-10970},

abstract = {Current approaches to introduce terminal alkynes for bioorthogonal reactions into biomolecules still present limitations in terms of either reactivity, selectivity, or adduct stability. We present a method for the ethynylation of cysteine residues based on the use of ethynylbenziodoxolone (EBX) reagents. The acetylene group is directly introduced onto the thiol group of cysteine and can be used for copper-catalyzed alkyne-azide cycloaddition (CuAAC) without further processing. Labeling proceeded with reaction rates comparable to or higher than the most often used iodoacetamide on peptides or maleimide on the antibody trastuzumab, and high cysteine selectivity was observed. The reagents were also used in living cells for cysteine proteomic profiling and displayed improved coverage of the cysteinome compared to previously reported iodoacetamide or hypervalent iodine reagents. Fine-tuning of the EBX reagents allows optimization of their reactivity and physical properties.},

note = {2018/30},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1503,

title = {Phylogenomic Classification and Biosynthetic Potential of the Fossil Fuel-Biodesulfurizing Rhodococcus Strain IGTS8},

author = {D. Thompson and V. Cognat and M. Goodfellow and S. Koechler and D. Heintz and C. Carapito and A. Van Dorsselaer and H. Mahmoud and V. Sangal and W. Ismail},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32733398},

doi = {10.3389/fmicb.2020.01417},

issn = {1664-302X (Print) 

1664-302X (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Front Microbiol},

volume = {11},

pages = {1417},

abstract = {Rhodococcus strain IGTS8 is the most extensively studied model bacterium for biodesulfurization of fossil fuels via the non-destructive sulfur-specific 4S pathway. This strain was initially assigned to Rhodococcus rhodochrous and later to Rhodococcus erythropolis thus making its taxonomic status debatable and reflecting the limited resolution of methods available at the time. In this study, phylogenomic analyses of the whole genome sequences of strain IGTS8 and closely related rhodococci showed that R. erythropolis and Rhodococcus qingshengii are very closely related species, that Rhodococcus strain IGTS8 is a R. qingshengii strain and that several strains identified as R. erythropolis should be re-classified as R. qingshengii. The genomes of strains assigned to these species contain potentially novel biosynthetic gene clusters showing that members of these taxa should be given greater importance in the search for new antimicrobials and other industrially important biomolecules. The plasmid-borne dsz operon encoding fossil fuel desulfurization enzymes was present in R. qingshengii IGTS8 and R. erythropolis XP suggesting that it might be transferable between members of these species.},

note = {2017/28},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1557,

title = {Structural basis for DNA recognition and allosteric control of the retinoic acid receptors RAR-RXR},

author = {J. Osz and A. G. McEwen and M. Bourguet and F. Przybilla and C. Peluso-Iltis and P. Poussin-Courmontagne and Y. Mely and S. Cianferani and C. M. Jeffries and D. I. Svergun and N. Rochel},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32974652},

doi = {10.1093/nar/gkaa697},

issn = {1362-4962 (Electronic) 

0305-1048 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Nucleic Acids Res},

volume = {48},

number = {17},

pages = {9969-9985},

abstract = {Retinoic acid receptors (RARs) as a functional heterodimer with retinoid X receptors (RXRs), bind a diverse series of RA-response elements (RAREs) in regulated genes. Among them, the non-canonical DR0 elements are bound by RXR-RAR with comparable affinities to DR5 elements but DR0 elements do not act transcriptionally as independent RAREs. In this work, we present structural insights for the recognition of DR5 and DR0 elements by RXR-RAR heterodimer using x-ray crystallography, small angle x-ray scattering, and hydrogen/deuterium exchange coupled to mass spectrometry. We solved the crystal structures of RXR-RAR DNA-binding domain in complex with the Rarb2 DR5 and RXR-RXR DNA-binding domain in complex with Hoxb13 DR0. While cooperative binding was observed on DR5, the two molecules bound non-cooperatively on DR0 on opposite sides of the DNA. In addition, our data unveil the structural organization and dynamics of the multi-domain RXR-RAR DNA complexes providing evidence for DNA-dependent allosteric communication between domains. Differential binding modes between DR0 and DR5 were observed leading to differences in conformation and structural dynamics of the multi-domain RXR-RAR DNA complexes. These results reveal that the topological organization of the RAR binding element confer regulatory information by modulating the overall topology and structural dynamics of the RXR-RAR heterodimers.},

note = {2018/07},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1554,

title = {How Reversible Are the Effects of Fumed Silica on Macrophages? A Proteomics-Informed View},

author = {A. Torres and B. Dalzon and V. Collin-Faure and H. Diemer and D. Fenel and G. Schoehn and S. Cianferani and M. Carriere and T. Rabilloud},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33003391},

doi = {10.3390/nano10101939},

issn = {2079-4991 (Print) 

2079-4991 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Nanomaterials (Basel)},

volume = {10},

number = {10},

abstract = {Synthetic amorphous silica is one of the most used nanomaterials, and numerous toxicological studies have studied its effects. Most of these studies have used an acute exposure mode to investigate the effects immediately after exposure. However, this exposure modality does not allow the investigation of the persistence of the effects, which is a crucial aspect of silica toxicology, as exemplified by crystalline silica. In this paper, we extended the investigations by studying not only the responses immediately after exposure but also after a 72 h post-exposure recovery phase. We used a pyrolytic silica as the test nanomaterial, as this variant of synthetic amorphous silica has been shown to induce a more persistent inflammation in vivo than precipitated silica. To investigate macrophage responses to pyrolytic silica, we used a combination of proteomics and targeted experiments, which allowed us to show that most of the cellular functions that were altered immediately after exposure to pyrolytic silica at a subtoxic dose, such as energy metabolism and cell morphology, returned to normal at the end of the recovery period. However, some alterations, such as the inflammatory responses and some aldehyde detoxification proteins, were persistent. At the proteomic level, other alterations, such as proteins implicated in the endosomal/lysosomal pathway, were also persistent but resulted in normal function, thus suggesting cellular adaptation.},

note = {2099/55},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1555,

title = {Structures of B. subtilis Maturation RNases Captured on 50S Ribosome with Pre-rRNAs},

author = {S. Oerum and T. Dendooven and M. Catala and L. Gilet and C. Degut and A. Trinquier and M. Bourguet and P. Barraud and S. Cianferani and B. F. Luisi and C. Condon and C. Tisne},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32991829},

doi = {10.1016/j.molcel.2020.09.008},

issn = {1097-4164 (Electronic) 

1097-2765 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {Mol Cell},

volume = {80},

number = {2},

pages = {227-236 e5},

abstract = {The pathways for ribosomal RNA (rRNA) maturation diverge greatly among the domains of life. In the Gram-positive model bacterium, Bacillus subtilis, the final maturation steps of the two large ribosomal subunit (50S) rRNAs, 23S and 5S pre-rRNAs, are catalyzed by the double-strand specific ribonucleases (RNases) Mini-RNase III and RNase M5, respectively. Here we present a protocol that allowed us to solve the 3.0 and 3.1 A resolution cryoelectron microscopy structures of these RNases poised to cleave their pre-rRNA substrates within the B. subtilis 50S particle. These data provide the first structural insights into rRNA maturation in bacteria by revealing how these RNases recognize and process double-stranded pre-rRNA. Our structures further uncover how specific ribosomal proteins act as chaperones to correctly fold the pre-rRNA substrates and, for Mini-III, anchor the RNase to the ribosome. These r-proteins thereby serve a quality-control function in the process from accurate ribosome assembly to rRNA processing.},

note = {2018/06},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1552,

title = {The Importance of Charge in Perturbing the Aromatic Glue Stabilizing the Protein-Protein Interface of Homodimeric tRNA-Guanine Transglycosylase},

author = {A. Nguyen and D. Nguyen and T. X. Phong Nguyen and M. Sebastiani and S. Dorr and O. Hernandez-Alba and F. Debaene and S. Cianferani and A. Heine and G. Klebe and K. Reuter},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33166460},

doi = {10.1021/acschembio.0c00700},

issn = {1554-8937 (Electronic) 

1554-8929 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {ACS Chem Biol},

volume = {15},

number = {11},

pages = {3021-3029},

abstract = {Bacterial tRNA-guanine transglycosylase (Tgt) is involved in the biosynthesis of the modified tRNA nucleoside queuosine present in the anticodon wobble position of tRNAs specific for aspartate, asparagine, histidine, and tyrosine. Inactivation of the tgt gene leads to decreased pathogenicity of Shigella bacteria. Therefore, Tgt constitutes a putative target for Shigellosis drug therapy. Since it is only active as homodimer, interference with dimer-interface formation may, in addition to active-site inhibition, provide further means to disable this protein. A cluster of four aromatic residues seems important to stabilize the homodimer. We mutated residues of this aromatic cluster and analyzed each mutated variant with respect to the dimer and thermal stability or enzyme activity by applying native mass spectrometry, a thermal shift assay, enzyme kinetics, and X-ray crystallography. Our structural studies indicate a strong influence of pH on the homodimer stability. Apparently, protonation of a histidine within the aromatic cluster supports the collapse of an essential structural motif within the dimer interface at slightly acidic pH.},

note = {2007/56},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1539,

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. Marques and D. Larrouy and I. Harant and C. Thalamas and E. Montastier and S. Caspar-Bauguil and V. Bourlier and G. Tavernier and J. L. Grolleau and A. Bouloumie and D. Langin and N. Viguerie and F. Bertile and S. Blanc and I. Glisezinski and D. O'Gorman and C. Moro},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32106110},

doi = {10.1172/jci.insight.131870},

issn = {2379-3708 (Electronic) 

2379-3708 (Linking)},

year  = {2020},

date = {2020-01-01},

journal = {JCI Insight},

volume = {5},

number = {6},

abstract = {We hypothesized that skeletal muscle contraction produces a cellular stress signal, triggering adipose tissue lipolysis to sustain fuel availability during exercise. The present study aimed at identifying exercise-regulated myokines, also known as exerkines, able to promote lipolysis. Human primary myotubes from lean healthy volunteers were submitted to electrical pulse stimulation (EPS) to mimic either acute intense or chronic moderate exercise. Conditioned media (CM) experiments with human adipocytes were performed. CM and human plasma samples were analyzed using unbiased proteomic screening and/or ELISA. Real-time qPCR was performed in cultured myotubes and muscle biopsy samples. CM from both acute intense and chronic moderate exercise increased basal lipolysis in human adipocytes. Growth and differentiation factor 15 (GDF15) gene expression and secretion increased rapidly upon skeletal muscle contraction. GDF15 protein was upregulated in CM from both acute and chronic exercise-stimulated myotubes. We further showed that physiological concentrations of recombinant GDF15 protein increased lipolysis in human adipose tissue, while blocking GDF15 with a neutralizing antibody abrogated EPS CM-mediated lipolysis. We herein provide the first evidence to our knowledge that GDF15 is a potentially novel exerkine produced by skeletal muscle contraction and able to target human adipose tissue to promote lipolysis.},

note = {2016/26},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1822,

title = {Large-Scale Proteomics Identifies Distinct Signatures for Richter Syndrome and De Novo Diffuse Large B-Cell Lymphoma: A French Study from the Filo Group},

author = {R. Morizot and S. Hergalant and R. Piucco and F. Bouclet and A. Quinquenel and C. Dartigeas and H. Auge and E. Tausch and S. Lomazzi and H. Busby and C. Tomowiak and V. Leblond and C. Thieblemont and F. Cymbalista and M. C. Bene and S. Stilgenbauer and R. Guieze and C. Carapito and A. Perrot and L. M. Fornecker and P. Feugier and J. Broseus},

url = {<Go to ISI>://WOS:000607205604298},

doi = {10.1182/blood-2020-137061},

issn = {0006-4971},

year  = {2020},

date = {2020-01-01},

journal = {Blood},

volume = {136},

note = {2015/10},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1821,

title = {Insight on the Impact of the Reduction Step on the Site-Directed Conjugation of an Anti-HER2 Cysteine-Engineered Antibody},

author = {J. Miret and M. Camps and M. Farras and R. Roman and S. Erb and S. Cianferani and A. Casablancas and J. J. Cairo},

url = {<Go to ISI>://WOS:000520610800007},

doi = {10.1002/slct.201903913},

issn = {2365-6549},

year  = {2020},

date = {2020-01-01},

journal = {Chemistryselect},

volume = {5},

number = {11},

pages = {3187-3190},

abstract = {Cysteine-based conjugation is one of the main antibody conjugation strategies for generating both heterogeneous and homogeneous Antibody Drug Conjugates (ADCs), being the reduction of the antibody a crucial step in these processes. In this work we have analysed the reduction conditions for the site-directed conjugation of an anti-HER2 (Human Epidermal Receptor 2) Trastuzumab_cys114 antibody to the cytotoxic drug vcMMAE (valine-citrulline monomethyl auristatin E), with an aimed average DAR (Drug-Antibody Ratio) of 2. Initial reduction was found to have a direct impact on the availability of free thiols for the conjugation: increasing of reducing agent concentration (until a molar excess of 50x) in the reduction step resulted in a lower proportion of naked antibody in the final ADC product and allowed us to obtain an ADC close to the DAR of interest. This work shows that reduction conditions must be adjusted in order to obtain the desired homogeneous ADC product.},

note = {2019/06/29},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1540,

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},

abstract = {Hibernating brown bears, Ursus arctos, undergo extended periods of inactivity and yet these large hibernators are resilient to muscle disuse atrophy. Physiological characteristics associated with atrophy resistance in bear muscle have been examined (e.g., muscle mechanics, neural activity) but roles for molecular signaling/regulatory mechanisms in the resistance to muscle wasting in bears still require investigation. Using quantitative reverse transcription PCR (RT-qPCR), the present study characterized the responses of 36 microRNAs linked with development, metabolism, and regeneration of skeletal muscle, in the vastus lateralis of brown bears comparing winter hibernating and summer active animals. Relative levels of mRNA of selected genes (mef2a, pax7, id2, prkaa1, and mstn) implicated upstream and downstream of the microRNAs were examined. Results indicated that hibernation elicited a myogenic microRNA, or "myomiR", response via MEF2A-mediated signaling. Upregulation of MEF2A-controlled miR-1 and miR-206 and respective downregulation of pax7 and id2 mRNA are suggestive of responses that promote skeletal muscle maintenance. Increased levels of metabolic microRNAs, such as miR-27, miR-29, and miR-33, may facilitate metabolic suppression during hibernation via mechanisms that decrease glucose uptake and fatty acid oxidation. This study identified myomiR-mediated mechanisms for the promotion of muscle regeneration, suppression of ubiquitin ligases, and resistance to muscle atrophy during hibernation mediated by observed increases in miR-206, miR-221, miR-31, miR-23a, and miR-29b. This was further supported by the downregulation of myomiRs associated with a muscle injury and inflammation (miR-199a and miR-223) during hibernation. The present study provides evidence of myomiR-mediated signaling pathways that are activated during hibernation to maintain skeletal muscle functionality in brown bears.},

note = {2011/34},

keywords = {},

pubstate = {published},

tppubtype = {article}

}