Author: "Institut Carnot" - Searchworks@Jio Institute Digital Library Search Results

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678 results on '"Institut Carnot"'

1. Gluten Sensibility in Elite Athletes (GLUTHEALTH)

Author: Centre de Recherche en Nutrition Humaine d'Auvergne, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, and Institut Carnot Qualiment
Published: 2018

2. Gene family expansions and transcriptome signatures uncover fungal adaptations to wood decay

Author: Joint Genome Institute (US), Institut Carnot Pasteur MS, l’Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (France), Conseil Régional Provence-Alpes-Côte d'Azur, Centre National de la Recherche Scientifique (France), Labex ARBRE, Conseil Régional de Lorraine, European Commission, Hungarian Academy of Sciences, Ministerio de Economía, Industria y Competitividad (España), Consejo Superior de Investigaciones Científicas (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Czech Science Foundation, Hage, Hayat [0000-0003-4118-1816], Miyauchi, Shingo [0000-0002-0620-5547], Virágh, Máté [0000-0002-2278-1288], Drula, Elodie [0000-0002-9168-5214], Min, Byoungnam [0000-0002-7469-088X], Favel, Anne [0000-0003-2255-3637], Lesage-Meessen, Laurence [0000-0003-2275-2978], Merényi, Z. [0000-0003-1114-3739], Eugenio, Laura I. de [0000-0002-0496-8663], Morin, Emmanuelle [0000-0002-7268-972X], Martínez, Ángel T. [0000-0002-1584-2863], Baldrian, Petr [0000-0002-8983-2721], Stursová, Martina [0000-0003-1387-6426], Martínez, María Jesús [0000-0003-2166-1097], Novotny, Cenek [0000-0003-3274-471X], Maurice, Sundy [0000-0002-5376-0981], Andreopoulos, William [0000-0001-9097-1123], LaButti, Kurt M. [0000-0002-5838-1972], Na, Hyunsoo [0000-0002-4386-017X], Barry, Kerrie [0000-0002-8999-6785], Lipzen, Anna [0000-0003-2293-9329], Henrissat, Bernard [0000-0002-3434-8588], Ahrendt, Steven [0000-0002-3029-2126], Grigoriev, Igor V. [0000-0002-3136-8903], Rosso, Marie-Noëlle [0000-0001-8317-7220], Hage, Hayat, Miyauchi, Shingo, Virágh, Máté, Drula, Elodie, Min, Byoungnam, Chaduli, Delphine, Navarro, David, Favel, Anne, Norest, Manon, Lesage-Meessen, Laurence, Bálint, Balázs, Merényi, Z., Eugenio, Laura I. de, Morin, Emmanuelle, Martínez, Ángel T., Baldrian, Petr, Stursová, Martina, Martínez, María Jesús, Novotny, Cenek, Magnuson, Jon K., Spatafora, Joey W., Maurice, Sundy, Pangilinan, Jasmyn, Andreopoulos, William, LaButti, Kurt M., Hundley, Hope, Na, Hyunsoo, Kuo, Alan, Barry, Kerrie, Lipzen, Anna, Henrissat, Bernard, Riley, Robert, Ahrendt, Steven, Nagy, Lazslo G., Grigoriev, Igor V., Martin, Francis, Rosso, Marie-Noëlle, Joint Genome Institute (US), Institut Carnot Pasteur MS, l’Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (France), Conseil Régional Provence-Alpes-Côte d'Azur, Centre National de la Recherche Scientifique (France), Labex ARBRE, Conseil Régional de Lorraine, European Commission, Hungarian Academy of Sciences, Ministerio de Economía, Industria y Competitividad (España), Consejo Superior de Investigaciones Científicas (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Czech Science Foundation, Hage, Hayat [0000-0003-4118-1816], Miyauchi, Shingo [0000-0002-0620-5547], Virágh, Máté [0000-0002-2278-1288], Drula, Elodie [0000-0002-9168-5214], Min, Byoungnam [0000-0002-7469-088X], Favel, Anne [0000-0003-2255-3637], Lesage-Meessen, Laurence [0000-0003-2275-2978], Merényi, Z. [0000-0003-1114-3739], Eugenio, Laura I. de [0000-0002-0496-8663], Morin, Emmanuelle [0000-0002-7268-972X], Martínez, Ángel T. [0000-0002-1584-2863], Baldrian, Petr [0000-0002-8983-2721], Stursová, Martina [0000-0003-1387-6426], Martínez, María Jesús [0000-0003-2166-1097], Novotny, Cenek [0000-0003-3274-471X], Maurice, Sundy [0000-0002-5376-0981], Andreopoulos, William [0000-0001-9097-1123], LaButti, Kurt M. [0000-0002-5838-1972], Na, Hyunsoo [0000-0002-4386-017X], Barry, Kerrie [0000-0002-8999-6785], Lipzen, Anna [0000-0003-2293-9329], Henrissat, Bernard [0000-0002-3434-8588], Ahrendt, Steven [0000-0002-3029-2126], Grigoriev, Igor V. [0000-0002-3136-8903], Rosso, Marie-Noëlle [0000-0001-8317-7220], Hage, Hayat, Miyauchi, Shingo, Virágh, Máté, Drula, Elodie, Min, Byoungnam, Chaduli, Delphine, Navarro, David, Favel, Anne, Norest, Manon, Lesage-Meessen, Laurence, Bálint, Balázs, Merényi, Z., Eugenio, Laura I. de, Morin, Emmanuelle, Martínez, Ángel T., Baldrian, Petr, Stursová, Martina, Martínez, María Jesús, Novotny, Cenek, Magnuson, Jon K., Spatafora, Joey W., Maurice, Sundy, Pangilinan, Jasmyn, Andreopoulos, William, LaButti, Kurt M., Hundley, Hope, Na, Hyunsoo, Kuo, Alan, Barry, Kerrie, Lipzen, Anna, Henrissat, Bernard, Riley, Robert, Ahrendt, Steven, Nagy, Lazslo G., Grigoriev, Igor V., Martin, Francis, and Rosso, Marie-Noëlle
Abstract: Because they comprise some of the most efficient wood-decayers, Polyporales fungi impact carbon cycling in forest environment. Despite continuous discoveries on the enzymatic machinery involved in wood decomposition, the vision on their evolutionary adaptation to wood decay and genome diversity remains incomplete., We combined the genome sequence information from 50 Polyporales species, including 26 newly sequenced genomes and sought for genomic and functional adaptations to wood decay through the analysis of genome composition and transcriptome responses to different carbon sources.The genomes of Polyporales from different phylogenetic clades showed poor conservation in macrosynteny, indicative of genome rearrangements. We observed different gene family expansion/contraction histories for plant cell wall degrading enzymes in core polyporoids and phlebioids and captured expansions for genes involved in signaling and regulation in the lineages of white rotters. Furthermore, we identified conserved cupredoxins, thaumatin-like proteins and Lytic Polysaccharide Monooxygenases with a yet uncharacterized appended module as new candidate players in wood decomposition.Given the current need for enzymatic toolkits dedicated to the transformation of renewable carbon sources, the observed genomic diversity among Polyporales strengthens the relevance of mining Polyporales biodiversity to understand the molecular mechanisms of wood decay.
Published: 2021

3. Tumor Control in RG2 Glioma-Bearing Rats: A Comparison Between Proton Minibeam Therapy and Standard Proton Therapy

Author: Institut National du Cancer (France), German Research Foundation, Institut Carnot Santé Animale, Prezado, Yolanda, Jouvion, Gregory, Guardiola, Consuelo, Gonzalez, Wilfredo, Juchaux, Marjorie, Bergs, Judith, Nauraye, Catherine, Labiod, Dalila, De Marzi, Ludovic, Pouzoulet, Frederic, Patriarca, Annalisa, Dendale, Remi, Institut National du Cancer (France), German Research Foundation, Institut Carnot Santé Animale, Prezado, Yolanda, Jouvion, Gregory, Guardiola, Consuelo, Gonzalez, Wilfredo, Juchaux, Marjorie, Bergs, Judith, Nauraye, Catherine, Labiod, Dalila, De Marzi, Ludovic, Pouzoulet, Frederic, Patriarca, Annalisa, and Dendale, Remi
Abstract: Proton minibeam radiation therapy (pMBRT) is a novel radiation therapy approach that exploits the synergies of proton therapy with the gain in normal tissue preservation observed upon irradiation with narrow, spatially fractionated, beams. The net gain in normal tissue sparing that has been shown by pMBRT may lead to the efficient treatment of very radioresistant tumors, which are currently mostly treated palliatively. The aim of this study was to perform an evaluation of the tumor effectiveness of proton minibeam radiation therapy for the treatment of RG2 glioma-bearing rats.
Published: 2019

4. A Novel Polyaminocarboxylate Compound To Treat Murine Pulmonary Aspergillosis by Interfering with Zinc Metabolism

Author: Institut Carnot Pasteur MS, Ministerio de Economía y Competitividad (España), Laskaris, Paris, Vicentefranqueira, Rocío, Helynck, Olivier, Jouvion, Grégory, Calera, José Antonio, Merle, Laurence du, Suzenet, Franck, Buron, Frédéric, Sousa, Rodolphe Alves de, Mansuy, Daniel, Cavaillon, Jean-Marc, Latgé, Jean Paul, Munier-Lehmann, Hélène, Ibrahim-Granet, Oumaima, Institut Carnot Pasteur MS, Ministerio de Economía y Competitividad (España), Laskaris, Paris, Vicentefranqueira, Rocío, Helynck, Olivier, Jouvion, Grégory, Calera, José Antonio, Merle, Laurence du, Suzenet, Franck, Buron, Frédéric, Sousa, Rodolphe Alves de, Mansuy, Daniel, Cavaillon, Jean-Marc, Latgé, Jean Paul, Munier-Lehmann, Hélène, and Ibrahim-Granet, Oumaima
Abstract: Aspergillus fumigatus can cause pulmonary aspergillosis in immunocompromised patients and is associated with a high mortality rate due to a lack of reliable treatment options. This opportunistic pathogen requires zinc in order to grow and cause disease. Novel compounds that interfere with fungal zinc metabolism may therefore be of therapeutic interest. We screened chemical libraries containing 59,223 small molecules using a resazurin assay that compared their effects on an A. fumigatus wild-type strain grown under zinc-limiting conditions and on a zinc transporter knockout strain grown under zinc-replete conditions to identify compounds affecting zinc metabolism. After a first screen, 116 molecules were selected whose inhibitory effects on fungal growth were further tested by using luminescence assays and hyphal length measurements to confirm their activity, as well as by toxicity assays on HeLa cells and mice. Six compounds were selected following a rescreening, of which two were pyrazolones, two were porphyrins, and two were polyaminocarboxylates. All three groups showed good in vitro activity, but only one of the polyaminocarboxylates was able to significantly improve the survival of immunosuppressed mice suffering from pulmonary aspergillosis. This two-tier screening approach led us to the identification of a novel small molecule with in vivo fungicidal effects and low murine toxicity that may lead to the development of new treatment options for fungal infections by administration of this compound either as a monotherapy or as part of a combination therapy.
Published: 2018

5. Sec22b is a critical and non-redundant regulator of plasma cell maintenance

Author: Amélie Bonaud, Laetitia Gargowitsch, Simon M. Gilbert, Elanchezhian Rajan, Pablo Canales-Herrerias, Daniel Stockholm, Nabila F. Rahman, Mark O. Collins, Hakan Taskiran, Danika L. Hill, Andres Alloatti, Nagham Alouche, Stéphanie Balor, Vanessa Soldan, Daniel Gillet, Julien Barbier, Françoise Bachelerie, Kenneth G. C. Smith, Julia Jellusova, Pierre Bruhns, Sebastian Amigorena, Karl Balabanian, Michelle A. Linterman, Andrew A. Peden, Marion Espéli, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Inflammation, microbiome, immunosurveillance (MI2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Cambridge [UK] (CAM), University of Sheffield [Sheffield], Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), School of Psychology [Cardiff University], Cardiff University, Technische Universität München = Technical University of Munich (TUM), Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, The Babraham Institute [Cambridge, UK], Monash University [Melbourne], Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad Nacional de Rosario [Santa Fe], Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-19-CE15-0019,PC-SEC,Impact des SNARE sur la biologie des plasmocytes(2019), ANR-14-ACHN-0008,AUTO-PLASMO,Analyse integrative de la biologie des plasmocytes normaux et pathologiques(2014), ANR-17-CE14-0019,OSTEOVALYMPH,Autocrinie et paracrinie de l'axe de signalisation CXCL12/CXCR4-CXCR7 dans la niche ostéo-vasculaire: impact sur la spécification et l'engagement lymphoïde des cellules souches hématopoïétiques(2017), ANR-18-CE15-0001,Autoimmuni-B,Etude de la rupture de tolérance dans une maladie humaine autoimmune médiée par les lymphocytes B(2018), The study was supported by the Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LabEx LERMIT) (M.E. and K.B.), an ANR JCJC grant (ANR-19-CE15-0019-01), an ANR @RAction grant (ANR-14-ACHN-0008), a 'Fondation ARC pour la recherche sur le cancer' grant (P JA20181208173), and a grant from IdEx Université Paris-Cité (ANR-18-IDEX-0001) to M.E., and an ANR PRC grant (ANR-17-CE14-0019) and an INCa grant (PRT-K 2017) to K.B. P.B. acknowledges funding from the French National Research Agency grant ANR-18-CE15-0001 project Autoimmuni-B, by the Institut Carnot Pasteur Microbes et Santé grant ANR-11-CARN-0017-01, the Institut Pasteur, and the Institut National de la Santé et de la Recherche Médicale (INSERM). M.A.L. is supported by Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0427, BBS/E/B/000C0428, and the Campus Capability Core Grant to the Babraham Institute). A.A.P. and M.O.C. were supported by a grant from the Biotechnology and Biological Sciences Research Council (BB/L022389/1). D.L.H. is supported by a National Health and Medical Research Council Australia Early-Career Fellowship (APP1139911). N.A. was supported by a PhD fellowship from the French Ministry for education and by a fourth year PhD fellowship from the 'Fondation ARC pour la recherche sur le cancer.' P.C.-H. was supported partly by a stipend from the Pasteur-Paris University (PPU) International PhD program, and by a fellowship from the French Fondation pour la Recherche Médicale (FRM). K.G.C.S. was supported by the Wellcome Trust (Programme Grant Number 083650/Z/07/Z). J.J’s research is supported by the German Research Foundation project number: 419193696 and through the CRC1335. H.T. is supported through the graduate school of the Max Planck Institute for Immunobiology and Epigenetics (IMPRS-IE) and through the CRC1335. The 'EMiLy' U1160 INSERM unit is a member of the OPALE Carnot institute, The Organization for Partnerships in Leukemia (Institut Carnot OPALE, Institut de Recherche Saint-Louis, Hôpital Saint-Louis, Paris, France. Web: www.opale.org. Email: contact@opale.org)., ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Bonaud, Amélie [0000-0002-4153-9171], Rajan, Elanchezhian [0000-0002-6257-3678], Canales-Herrerias, Pablo [0000-0002-1865-6476], Stockholm, Daniel [0000-0002-5069-5256], Collins, Mark O [0000-0002-7656-4975], Taskiran, Hakan [0000-0002-2690-3887], Alloatti, Andres [0000-0003-0555-0653], Gillet, Daniel [0000-0003-0477-3599], Bruhns, Pierre [0000-0002-4709-8936], Balabanian, Karl [0000-0002-0534-3198], Linterman, Michelle A [0000-0001-6047-1996], Peden, Andrew A [0000-0003-0144-7712], Espéli, Marion [0000-0001-5005-1664], and Apollo - University of Cambridge Repository
Subjects: R-SNARE Proteins, mitochondria, Mice, endoplasmic reticulum, Multidisciplinary, plasma cell, SNARE, antibody, [SDV]Life Sciences [q-bio], Plasma Cells, Animals, Biological Transport, SNARE Proteins
Abstract: Despite the essential role of plasma cells in health and disease, the cellular mechanisms controlling their survival and secretory capacity are still poorly understood. Here, we identified the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Sec22b as a unique and critical regulator of plasma cell maintenance and function. In the absence of Sec22b, plasma cells were hardly detectable and serum antibody titers were dramatically reduced. Accordingly, Sec22b -deficient mice fail to mount a protective immune response. At the mechanistic level, we demonstrated that Sec22b contributes to efficient antibody secretion and is a central regulator of plasma cell maintenance through the regulation of their transcriptional identity and of the morphology of the endoplasmic reticulum and mitochondria. Altogether, our results unveil an essential and nonredundant role for Sec22b as a regulator of plasma cell fitness and of the humoral immune response.
Published: 2023
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6. Cytidine deaminase deficiency in tumor cells is associated with sensitivity to a naphthol derivative and a decrease in oncometabolite levels

Author: Hamza Mameri, Géraldine Buhagiar-Labarchède, Gaëlle Fontaine, Céline Corcelle, Caroline Barette, Rosine Onclercq-Delic, Claire Beauvineau, Florence Mahuteau-Betzer, Mounira Amor-Guéret, Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Intégrité du génome, ARN et cancer, Institut Curie [Paris]-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Chimie et modélisation pour la biologie du cancer (CMBC), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Genetics and Chemogenomics (GenChem), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), and Cancéropôle Ile de France, Ligue Nationale contre le Cancer, Fondation ARC and Curie Cancer (Institut Carnot) , Institut Curie(Innov’booster program, Institut Carnot ), CNRS (Prematuration program ) and Ligue Nationale Contre le Cancer (Comité de l'Essonne).
Subjects: Pharmacology, Cell metabolism, Cytidine deaminase, Cancer therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Naphthols, Cell Biology, Cellular and Molecular Neuroscience, MAPT, Humans, Molecular Medicine, Molecular Biology, HeLa Cells, Drug sensitivity
Abstract: Identifying new molecular targets for novel anticancer treatments is a major challenge in clinical cancer research. We have shown that cytidine deaminase (CDA) expression is downregulated in about 60% of cancer cells and tissues. In this study, we aimed to develop a new anticancer treatment specifically inhibiting the growth of CDA-deficient tumor cells. High-throughput screening of a chemical library led to the identification of a naphthol derivative, X55, targeting CDA-deficient tumor cells preferentially, without affecting the growth of non-tumoral cells regardless of CDA expression status. Metabolomic profiling revealed that CDA-deficient HeLa cells differed markedly from control HeLa cells. X55 treatment had a moderate effect on control cells, but greatly disturbed the metabolome of CDA-deficient HeLa cells, worsening the deregulation of many metabolites. In particular, the levels of the three oncometabolites, fumarate, succinate and 2-hydroxyglutarate, were significantly lower in CDA-depleted cells, and this decrease in levels was exacerbated by X55 treatment, revealing an unexpected link between CDA deficiency, mitochondrial function and X55 response. Finally, we identified strong downregulation of MAPT (encoding Tau, a microtubule associated protein) expression as a reliable predictive marker for tumor cell X55 sensitivity.
Published: 2022
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7. Mining zebrafish microbiota reveals key community-level resistance against fish pathogen infection

Author: Valérie Briolat, Stevenn Volant, Sebastian Bruchmann, Susanne Häussler, Joaquín Bernal-Bayard, Franziska A. Stressmann, Bianca Audrain, Jean-Marc Ghigo, Amine Ghozlane, David Pérez-Pascual, Eric Duchaud, Jean-Pierre Levraud, Olaya Rendueles, Génétique des Biofilms - Genetics of Biofilms, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Macrophages et Développement de l’Immunité, Helmholtz Centre for Infection Research (HZI), University of Cambridge [UK] (CAM), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by the Institut Pasteur, the French Government’s Investissement d’Avenir program: Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID to J.M.G.), the Fondation pour la Recherche Médicale (grant no. DEQ20180339185 to J.M.G.). F.S. was the recipient of a post-doctoral Marie Curie fellowship from the EU-FP7 programme, J.B.B. was the recipient of a long-term post-doctoral fellowship from the Federation of European Biochemical Societies(FEBS) and by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 842629 D.P-P was supported by an Institut Carnot MS Postdoctoral fellowship., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany., This work was supported by the Institut Pasteur, the French Government’s Investissement d’Avenir program: Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID to J-MG.), the Fondation pour la Recherche Médicale (grant no. DEQ20180339185 to J-MG). FS was the recipient of a post-doctoral Marie Curie fellowship from the EU-FP7 program, JBB was the recipient of a long-term post-doctoral fellowship from the Federation of European Biochemical Societies (FEBS) and by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 842629. DP-P was supported by an Institut Carnot MS Postdoctoral fellowship., European Project: 842629,Salmofish, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Exogenous bacteria, Chryseobacterium, Colonisation resistance, Flavobacterium, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Microbiology, Article, 03 medical and health sciences, medicine, MESH: Microbiota, Animals, MESH: Animals, MESH: Zebrafish, Pathogen, Zebrafish, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Innate immune system, biology, 030306 microbiology, Microbiota, fungi, Commensalism, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Dysbiosis, Flavobacterium columnare, Dysbiosis, MESH: Flavobacterium / genetics, Bacteria
Abstract: The long-known resistance to pathogens provided by host-associated microbiota fostered the notion that adding protective bacteria could prevent or attenuate infection. However, the identification of endogenous or exogenous bacteria conferring such protection is often hindered by the complexity of host microbial communities. Here, we used zebrafish and the fish pathogen Flavobacterium columnare as a model system to study the determinants of microbiota-associated colonization resistance. We compared infection susceptibility in germ-free, conventional and re-conventionalized larvae and showed that a consortium of 10 culturable bacterial species are sufficient to protect zebrafish. Whereas survival to F. columnare infection does not rely on host innate immunity, we used antibiotic dysbiosis to alter zebrafish microbiota composition, leading to the identification of two different protection strategies. We first identified that the bacterium Chryseobacterium massiliae individually protects both larvae and adult zebrafish. We also showed that an assembly of 9 endogenous zebrafish species that do not otherwise protect individually confer a community-level resistance to infection. Our study therefore provides a rational approach to identify key endogenous protecting bacteria and promising candidates to engineer resilient microbial communities. It also shows how direct experimental analysis of colonization resistance in low-complexity in vivo models can reveal unsuspected ecological strategies at play in microbiota-based protection against pathogens.
Published: 2020
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8. Irreversible inhibitors of the proline racemase unveil innovative mechanism of action as antibacterial agents against Clostridioides difficile

Author: Cécile Gateau, Guilherme D. Melo, Philippe Uriac, Olivier Tasseau, Jacques Renault, Arnaud Blondel, Nicolas Gouault, Frédéric Barbut, Paola Minoprio, Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur [Paris], Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Processus infectieux à Trypanosomatidés - Trypanosomatids Infectious Processes, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bioinformatique structurale - Structural Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Carnot Pasteur Microbes & Santé CARNOT/MS (ANR-16-CARN-0023-01 - non référencé dans AuréHAL), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Carnot Pasteur Microbes & Santé CARNOT/MS (ARN-16-CARN-0023-01 - non référencé dans AuréHAL)
Subjects: Pharmacology, 0303 health sciences, Proline, 010405 organic chemistry, Clostridioides difficile, enzyme inhibitors, structure-activity relationship, Organic Chemistry, 01 natural sciences, Biochemistry, 3. Good health, 0104 chemical sciences, Anti-Bacterial Agents, 03 medical and health sciences, antibacterial, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, proline racemase, Drug Discovery, parasitic diseases, Molecular Medicine, [CHIM]Chemical Sciences, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Amino Acid Isomerases
Abstract: International audience; Proline racemases (PRAC), catalyzing the l-proline and d-proline interconversion, are essential factors in eukaryotic pathogens such as Trypanosoma cruzi, Trypanosoma vivax, and Clostridioides difficile. If the discovery of irreversible inhibitors of T. cruzi PRAC (TcPRAC) led to innovative therapy of the Chagas disease, no inhibitors of CdPRAC have been discovered to date. However, C. difficile, due to an increased incidence in recent years, is considered as a major cause of health threat. In this work, we have taken into account the similarity between TcPRAC and CdPRAC enzymes to design new inhibitors of CdPRAC. Starting from (E) 4-oxopent-2-enoic acid TcPRAC irreversible inhibitors, we synthesized 4-aryl substituted analogs and evaluated their CdPRAC enzymatic inhibition against eleven strains of C. difficile. This study resulted in promising candidates and allowed for identification of (E)-4-(3-bromothiophen-2-yl)-4-oxobut-2-enoic acid 20 that was chosen for complementary in vivo studies and did not reveal in vivo toxicity.
Published: 2021
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9. Refining diffuse large B-cell lymphoma subgroups using integrated analysis of molecular profiles

Author: Bettina Fabiani, Sylvain Mareschal, Pascaline Etancelin, Tony Petrella, Fabrice Jardin, Bruno Tesson, Sydney Dubois, Jean-Philippe Jais, Christiane Copie-Bergman, Gilles Salles, Elodie Bohers, Corinne Haioun, Pierre-Julien Viailly, Thierry Jo Molina, Philippe Ruminy, Karen Leroy, Hervé Tilly, Pauline Peyrouze, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Carnot CALYM [Pierre-Benite], Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université Lille 2 - Faculté de Médecine, INSERM U955, équipe 9, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de pathologie, Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département d'Hématologie, Institut Carnot Lymphome (CALYM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine Henri Warembourg - Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre de pathologie [Dijon]
Subjects: 0301 basic medicine, Male, Research paper, Key genes, Transcriptomic variability, DNA Copy Number Variations, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Locus (genetics), Computational biology, Independent component analysis, Biology, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], hemic and lymphatic diseases, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Copy-number variation, Gene signatures, prognosis, Genetic Association Studies, lcsh:R5-920, Gene Expression Profiling, lcsh:R, Gene signatures, Chromosome Mapping, Computational Biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Molecular Sequence Annotation, General Medicine, Diffuse large B-cell lymphoma, Gene signature, medicine.disease, Immunohistochemistry, Gene expression profiling, 030104 developmental biology, 030220 oncology & carcinogenesis, Affymetrix genechip, Female, prognosis, Lymphoma, Large B-Cell, Diffuse, lcsh:Medicine (General)
Abstract: Background: Gene expression profiling (GEP), next-generation sequencing (NGS) and copy number variation (CNV) analysis have led to an increasingly detailed characterization of the genomic profiles of DLBCL. The aim of this study was to perform a fully integrated analysis of mutational, genomic, and expression profiles to refine DLBCL subtypes. A comparison of our model with two recently published integrative DLBCL classifiers was carried out, in order to best reflect the current state of genomic subtypes. Methods: 223 patients with de novo DLBCL from the prospective, multicenter and randomized LNH-03B LYSA clinical trials were included. GEP data was obtained using Affymetrix GeneChip arrays, mutational profiles were established by Lymphopanel NGS targeting 34 key genes, CNV analysis was obtained by array CGH, and FISH and IHC were performed. Unsupervised independent component analysis (ICA) was applied to GEP data and integrated analysis of multi-level molecular data associated with each component (gene signature) was performed. Findings: ICA identified 38 components reflecting transcriptomic variability across our DLBCL cohort. Many of the components were closely related to well-known DLBCL features such as cell-of-origin, stromal and MYC signatures. A component linked to gain of 19q13 locus, among other genomic alterations, was significantly correlated with poor OS and PFS. Through this integrated analysis, a high degree of heterogeneity was highlighted among previously described DLBCL subtypes. Interpretation: The results of this integrated analysis enable a global and multi-level view of DLBCL, as well as improve our understanding of DLBCL subgroups. Keywords: Diffuse large B-cell lymphoma, Independent component analysis, Transcriptomic variability, Gene signatures, prognosis
Published: 2019
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10. X-Light : an open-source software written in Python to determine the residual stress by X-ray diffraction

Author: Tu-Quoc-Sang Pham, Guillaume Geandier, Benoit Malard, Charles Mareau, Nicolas Ratel-Ramond, Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre d'élaboration de matériaux et d'études structurales (CEMES), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Angevin de Mécanique, Procédés et InnovAtion (LAMPA), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and This work was supported by Institut CARNOT ICEEL and Institut CARNOT Chimie Balard CIRIMAT, which are acknowledged for their support under the ECOMAM project No. 408-16AC02
Subjects: Diffraction, Matériaux [Sciences de l'ingénieur], Synchrotron radiation, residual stress, General Biochemistry, Genetics and Molecular Biology, [SPI.MAT]Engineering Sciences [physics]/Materials, Stress (mechanics), Software, X-Light software, Residual stress, Mécanique: Mécanique des matériaux [Sciences de l'ingénieur], pseudo-Voigt, Graphical user interface, computer.programming_language, Physics, Lorentzian, fundamental X-ray diffraction method, business.industry, Pearson VII, Voigt, Python (programming language), Computational physics, sin 2 method, X-ray crystallography, Gaussian, business, computer, sin2 method
Abstract: X-Light is an open-source software that is written in Python with a graphical user interface. X-Light was developed to determine residual stress by X-ray diffraction. This software can process the 0D, 1D and 2D diffraction data obtained with laboratory diffractometers or synchrotron radiation. X-Light provides several options for stress analysis and five functions to fit a peak: Gauss, Lorentz, Pearson VII, pseudo-Voigt and Voigt. The residual stress is determined by the conventional sin2ψ method and the fundamental method.
Published: 2021
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11. Reverting the mode of action of the mitochondrial FOF1-ATPase by Legionella pneumophila preserves its replication niche

Author: Tobias Sahr, Platon L, Dramé M, Pedro Escoll, Carmen Buchrieser, Christophe Rusniok, Silke Schmidt, Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), Université de Paris (UP), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), This research was funded by the Institut Pasteur, DARRI - Institut Carnot - Microbe et santé (grant number INNOV-SP10-19) to PE, the Agence National de Recherche (grant number ANR-10-LABX- 62-IBEID) and the Fondation de la Recherché Médicale (FRM) (grant number EQU201903007847) to CB, and the Région Ile-de-France (program DIM1Health) to PBI (part of FranceBioImaging, ANR-10-INSB-04-01). MD was supported by the Ecole Doctorale FIRE – 'Programme Bettencourt'. SS was supported by the Pasteur Paris-University (PPU) International PhD Program., We acknowledge C.B.’s, P. Glaser’s lab members and F. Stavru at Institut Pasteur for fruitful discussions. We thank N. Aulner, A. Danckaert, Photonic BioImaging (PBI) UTechS and M. Hassan, Center for Translational Science (CRT) at Institut Pasteur, for support, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Mémoires - Université de Montpellier - Faculté des sciences (UM FS), Faculté des sciences de Paris, Université de Paris (1896-1970), Collège Doctoral, This research was funded by the Institut Pasteur, DARRI-Institut Carnot-Microbe et santé (grant number INNOV-SP10-19) to PE, the Agence National de Recherche (grant number ANR-10-LABX-62-IBEID to CB and ANR-21-CE15-0038-01 to PE), the Fondation de la Recherché Médicale (FRM) (grant number EQU201903007847) to CB, and the Région Ile-de-France (program DIM1Health) to PBI (part of FranceBioImaging, ANR-10-INSB-04–01). MD was supported by the Ecole Doctorale FIRE – 'Programme Bettencourt.' SS was supported by the Pasteur Paris-University (PPU) International PhD Program., We acknowledge CB’s, P Glaser’s lab members, and F Stavru at Institut Pasteur for fruitful discussions. We specially thank Daniel Schator for help and discussions regarding HEK-293 infection and transfec- tion. We thank N Aulner, A Danckaert, Photonic BioImaging (PBI) UTechS and M Hassan, Center for Translational Science (CRT) at Institut Pasteur, for support., ANR-21-CE15-0038,MITOBAC,Interactions Métaboliques Hôte-Pathogène: Comment des Bactéries Intracellulaires détournent l'OXPHOS Mitochondriale pendant l'infection(2021), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Cité (UPCité)
Subjects: Programmed cell death, QH301-705.5, MESH: Mitochondria, Science, infectious disease, FOF1-ATPase, Oxidative phosphorylation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Legionella pneumophila, MESH: Proton-Translocating ATPases, 03 medical and health sciences, 0302 clinical medicine, mitochondrial membrane potential, MESH: Adenosine Triphosphate, Biology (General), MESH: Bacterial Proteins, MESH: Type IV Secretion Systems, 030304 developmental biology, Membrane potential, 0303 health sciences, Effector, microbiology, MESH: Mitochondrial Proteins, Metabolism, Microphthalmia-associated transcription factor, biology.organism_classification, MESH: Legionella pneumophila, OXPHOS, 3. Good health, Cell biology, macrophages, mitochondria, cell death, Medicine, Reprogramming, 030217 neurology & neurosurgery
Abstract: Legionella pneumophila, the causative agent of Legionnaires’ disease, a severe pneumonia, injects via a type-IV-secretion-system (T4SS) more than 300 proteins into macrophages, its main host cell in humans. Certain of these proteins are implicated in reprogramming the metabolism of infected cells by reducing mitochondrial oxidative phosphorylation (OXPHOS) early after infection. Here we show that despite reduced OXPHOS, the mitochondrial membrane potential (Δψm) is maintained during infection of primary human monocyte-derived macrophages (hMDMs). We reveal that L. pneumophila reverses the ATP-synthase activity of the mitochondrial FOF1-ATPase to ATP-hydrolase activity in a T4SS-dependent manner, which leads to a conservation of the Δψm, preserves mitochondrial polarization and prevents macrophage cell death. Analyses of T4SS effectors known to target mitochondrial functions revealed that LpSpl is partially involved in conserving the Δψm, but not LncP and MitF. The inhibition of the L. pneumophila-induced “reverse mode” of the FOF1-ATPase collapsed the Δψm and caused cell death in infected cells. Single-cell analyses suggested that bacterial replication occurs preferentially in hMDMs that conserved the Δψm and showed delayed cell death. This direct manipulation of the mode of activity of the FOF1-ATPase is a newly identified feature of L. pneumophila allowing to delay host cell death and thereby to preserve the bacterial replication niche during infection.
Published: 2021
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12. Lymphoma Heterogeneity Unraveled by Single-Cell Transcriptomics

Author: Loic Ysebaert, Anne Quillet-Mary, Marie Tosolini, Frederic Pont, Camille Laurent, Jean-Jacques Fournié, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d’Excellence ‘TOUCAN’ [Toulouse], Institut Carnot CALYM [Pierre-Benite], CHU Toulouse [Toulouse], Service d'Hématologie [CHU Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), QUILLET-MARY, Anne, Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Carnot Lymphome (CALYM)
Subjects: 0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Lymphoma, Immune checkpoint inhibitors, [SDV]Life Sciences [q-bio], Review, Transcriptome, Functional diversity, 0302 clinical medicine, Immunology and Allergy, Precision Medicine, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], High-Throughput Nucleotide Sequencing, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Prognosis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Combined Modality Therapy, 3. Good health, Treatment Outcome, Drugs response, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.IMM]Life Sciences [q-bio]/Immunology, Single-Cell Analysis, lcsh:Immunologic diseases. Allergy, bioinformatics analysis, Bioinformatics analysis, [SDV.IMM] Life Sciences [q-bio]/Immunology, Single cell transcriptomics, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, Biology, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Biomarkers, Tumor, Humans, single-cell RNA sequencing (scRNA-seq), Gene Expression Profiling, Computational Biology, Molecular Sequence Annotation, medicine.disease, Precision medicine, microenvironment, 030104 developmental biology, cell of origin (COO), lcsh:RC581-607
Abstract: International audience; High-definition transcriptomic studies through single-cell RNA sequencing (scRNA-Seq) have revealed the heterogeneity and functionality of the various microenvironments across numerous solid tumors. Those pioneer studies have highlighted different cellular signatures correlated with clinical response to immune checkpoint inhibitors. scRNA-Seq offers also a unique opportunity to unravel the intimate heterogeneity of the ecosystems across different lymphoma entities. In this review, we will first cover the basics and future developments of the technology, and we will discuss its input in the field of translational lymphoma research, from determination of cell-of-origin and functional diversity, to monitoring of anti-cancer targeted drugs response and toxicities, and how new improvements in both data collection and interpretation will further foster precision medicine in the upcoming years.
Published: 2021
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13. Phased differentiation of γδ T and T CD8 tumorinfiltrating lymphocytes revealed by single-cell transcriptomics of human cancers

Author: Pauline Gravelle, Marie Tosolini, Juan-Pablo Cerapio, Frédéric Pont, Maha Ayyoub, Camille Laurent, Virginie Féliu, Carine Valle, Anne Quillet-Mary, Alejandra Martinez, Loic Ysebaert, Camille-Charlotte Balança, Christel Devaud, Jean-Jacques Fournié, Don-Marc Franchini, Frédéric Lopez, Marion Perrier, Jean Pierre Delord, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d’Excellence ‘TOUCAN’ [Toulouse], Institut Carnot CALYM [Pierre-Benite], CHU Toulouse [Toulouse], Institut Claudius Regaud, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), QUILLET-MARY, Anne, Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Carnot Lymphome (CALYM), and Fournié, jean-jacques
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, Ontogeny, Single cell transcriptomics, [SDV]Life Sciences [q-bio], Immunology, Antigen specificity, [SDV.CAN]Life Sciences [q-bio]/Cancer, CD8-Positive T-Lymphocytes, Biology, Mice, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, T-Lymphocyte Subsets, Neoplasms, Animals, Humans, Immunology and Allergy, RC254-282, ComputingMilieux_MISCELLANEOUS, Gamma-delta lymphocyte, Original Research, 030304 developmental biology, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Tumor-infiltrating lymphocytes, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cell Differentiation, Receptors, Antigen, T-Cell, gamma-delta, scRNAseq, differentiation, RC581-607, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunologic diseases. Allergy, Transcriptome, CD8, CD8/Lymphocytes, Research Article, Homing (hematopoietic)
Abstract: International audience; γδ T lymphocytes diverge from conventional T CD8 lymphocytes for ontogeny, homing, and antigen specificity, but whether their differentiation in tumors also deviates was unknown. Using innovative analyses of our original and ~150 published single-cell RNA sequencing datasets validated by phenotyping of human tumors and murine models, here we present the first high-resolution view of human γδ T cell differentiation in cancer. While γδ T lymphocytes prominently encompass TCRVγ9 cells more differentiated than T CD8 in healthy donor's blood, a different scenario is unveiled in tumors. Solid tumors and lymphomas are infiltrated by a majority of TCRVγnon9 γδ T cells which are quantitatively correlated and remarkably aligned with T CD8 for differentiation, exhaustion, gene expression profile, and response to immune checkpoint therapy. This cancer-wide association is critical for developing cancer immunotherapies.
Published: 2021
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14. Reassessment of the risk of birth defects due to Zika virus in Guadeloupe, 2016

Author: Funk, Anna L, Hoen, Bruno, Vingdassalom, Ingrid, Ryan, Catherine, Kadhel, Philippe, Schepers, Kinda, Gaete, Stanie, Tressieres, Benoît, Fontanet, Arnaud, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre Pluridisciplinaire de Diagnostic Prénatal [Pointe-à-Pitre], CHU Pointe-à-Pitre/Abymes [Guadeloupe], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université des Antilles (Pôle Guadeloupe), Université des Antilles (UA), Institut Carnot Pasteur Maladie Infectieuse ANR-11-CARN-017-01, This work was supported by the French Ministry of Health (Soutien Exceptionnel à la Recherche et à l’Innovation) which was received by BH, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases project (ANR-10-LABEX-62-IBEID) which was received by AF, the European Union’s Horizon 2020 Research and Innovation Program through the ZikAlliance consortium (Grant Agreement no. 73458) which was received by BH, and by INSERM which was received by BH. ALF was part of the Pasteur – Paris University (PPU) International PhD Program until late 2018, from which she received funding from the Institut Carnot Pasteur Maladie Infectieuse (ANR 11-CARN 017-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 734548,ZIKAlliance(2016), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Chard-Hutchinson, Xavier, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and A global alliance for Zika virus control and prevention - ZIKAlliance - 2016-10-01 - 2019-09-30 - 734548 - VALID
Subjects: RNA viruses, Epidemiology, Maternal Health, Pathology and Laboratory Medicine, Geographical locations, Cohort Studies, Families, Medical Conditions, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Morphogenesis, Prospective Studies, Pregnancy Complications, Infectious, Children, Guadeloupe, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Anthropometry, Zika Virus Infection, Obstetrics and Gynecology, Middle Aged, Medical Microbiology, Viral Pathogens, Viruses, Microcephaly, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Pathogens, Anatomy, Infants, Research Article, Adult, Microbiology, Congenital Abnormalities, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Congenital Disorders, Humans, Birth Defects, Microbial Pathogens, Caribbean, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Biology and life sciences, Flaviviruses, Organisms, Infant, Newborn, Zika Virus, Age Groups, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Medical Risk Factors, People and Places, North America, Women's Health, Population Groupings, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Developmental Biology
Abstract: Background In the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was 7.0% (95%CI: 5.0 to 9.5) among foetuses/infants of 546 women with symptomatic RT-PCR confirmed ZIKV infection during pregnancy. Many of these defects were isolated measurement-based microcephaly (i.e. without any detected brain or clinical abnormalities) or mild neurological conditions. We wanted to estimate the proportion of such minor findings among live births of women who were pregnant in the same region during the outbreak period but who were not infected with ZIKV. Methods In Guadeloupe, pregnant women were recruited at the time of delivery and tested for ZIKV infection. The outcomes of live born infants of ZIKV non-infected women were compared to those of ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA prospective cohort. Results Of 490 live born infants without exposure to ZIKV, 42 infants (8.6%, 95%CI: 6.2–11.4) had mild abnormalities that have been described as ‘potentially linked to ZIKV infection’; all but one of these was isolated measurement-based microcephaly. Among the 241 live born infants with ZIKV exposure, the proportion of such abnormalities, using the same definition, was similar (6.6%, 95%CI: 3.8–10.6). Conclusions Isolated anthropometric abnormalities and mild neurological conditions were as prevalent among infants with and without in-utero ZIKV exposure. If such abnormalities had not been considered as ‘potentially linked to ZIKV’ in the original prospective cohort in Guadeloupe, the overall estimate of the risk of birth defects considered due to the virus would have been significantly lower, at approximately 1.6% (95% CI: 0.4–4.1). Trial registration ClinicalTrials.gov (NCT02916732), Author summary Microcephaly defined using growth charts occurs naturally in some healthy infants. Nonetheless, in many recent Zika virus studies, such measurement-based microcephaly and other common mild abnormalities have been automatically attributed to viral exposure during pregnancy. For example, in 2016 in Guadeloupe, we did a cohort study and estimated that the risk of Zika virus related birth defects was 7%. However, most of the ‘abnormal’ live born infants that contributed to this risk estimate were considered healthy by pediatricians, but were found to have measurement-based microcephaly during data analysis. In the current study, we did a cross-sectional evaluation of infants live born in 2016 in Guadeloupe, but whose mothers were not infected with Zika virus during pregnancy. We found that Zika virus unexposed live born infants had similar proportions of measurement-based microcephaly and mild neurological abnormalities as exposed live born infants. If only severe and uncommon birth defects were considered linked to Zika virus in our original cohort study, our risk estimate would have been significantly lower. This research shows that it is important to consider baseline risks and control comparisons when establishing key parameters for emerging diseases, such as Zika virus.
Published: 2021
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15. Rapid Genomic Characterization of SARS-CoV-2 by Direct Amplicon-Based Sequencing Through Comparison of MinION and Illumina iSeq100TM System

Author: Véronique Hourdel, Aurélia Kwasiborski, Séverine Matheus, Jean-Claude Manuguerra, Valérie Caro, Christophe Batéjat, Jessica Vanhomwegen, Charlotte Balière, Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris], This work was made possible thanks to financial support obtained through the «URGENCE Nouveau Coronavirus» fundraising campaign of Institut Pasteur. This project also received funding from the French Institut Carnot Pasteur 'Microbes et Santé' (ANR 19 CARN 0023-01) and Institut Carnot 'France Futur Élevage' (ANR 19 CARN 0012-01), in the framework of the FIELD project., We acknowledged all the members of the Laboratory for Urgent Response to Biological Threats (Institut Pasteur) who are involved in the COVID-19 diagnosis and India Leclercq for her support in viral isolation., and Institut Pasteur [Paris] (IP)
Subjects: Microbiology (medical), amplicon-based sequencing, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lcsh:QR1-502, MinION, Computational biology, Biology, real-time genome sequencing, Genome, Microbiology, DNA sequencing, lcsh:Microbiology, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Methods, 030304 developmental biology, 0303 health sciences, 030306 microbiology, SARS-CoV-2, COVID-19, Amplicon, medicine.disease, biology.organism_classification, 3. Good health, Minion, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Middle East respiratory syndrome, iSeq100TM system, Betacoronavirus
Abstract: International audience; Global human health is increasingly challenged by emerging viral threats, especially those observed over the last 20 years with coronavirus-related human diseases, such as the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS). Recently, in late December 2019, a novel Betacoronavirus, SARS-CoV-2, originating from the Chinese city of Wuhan, emerged and was then identified as the causative agent of a new severe form of pneumonia, COVID-19. Real-time genome sequencing in such viral outbreaks is a key issue to confirm identification and characterization of the involved pathogen and to help establish public health measures. Here, we implemented an amplicon-based sequencing approach combined with easily deployable next-generation sequencers, the small and hand-held MinION sequencer and the latest most compact Illumina sequencer, the iSeq100TM system. Our results highlighted the great potential of the amplicon-based approach to obtain consensus genomes of SARS-CoV-2 from clinical samples in just a few hours. Both these mobile next-generation sequencers are proven to be efficient to obtain viral sequences and easy to implement, with a minimal laboratory environment requirement, providing useful opportunities in the field and in remote areas.
Published: 2020
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16. The Spatial Heterogeneity of the Gut Limits Predation and Fosters Coexistence of Bacteria and Bacteriophages

Author: Luisa De Sordi, Thierry Pedron, Claudia Eberl, Lorenzo Chaffringeon, Quentin Lamy-Besnier, Pascal Campagne, Marion Bérard, Laurent Debarbieux, Bärbel Stecher, Marta Lourenço, Bactériophage, bactérie, hôte - Bacteriophage, bacterium, host, Institut Pasteur [Paris], Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Max von Pettenkofer-Institut for Hygiene and Medical Microbiology, Ludwig-Maximilians-Universität München (LMU), Animalerie centrale (Plate-forme), German Center for Infection Research, Partnersite Munich (DZIF), Institut Carnot Pasteur Maladie Infectieuse ANR-11-CARN-017-01, M.L. is part of the Pasteur - Paris University (PPU) International PhD Program. M.L. is funded by Institut Carnot Pasteur Maladie Infectieuse (ANR 11-CARN 017-01). L.D.S. is funded by a Roux-Cantarini fellowship from the Institut Pasteur (Paris, France). L.C. is funded by a PhD fellowships from the Ministère de l’Enseignement Supérieur et de la Recherche, France, École Doctorale n°394. Q.L.-B. is funded by École Doctorale FIRE - Program Bettencourt. B.S. is supported by the German Center of Infection Research (DZIF), the Center for Gastrointestinal Microbiome Research (CEGIMIR), the DFG, Germany, Priority Programme SPP1656 (STE 1971/4-2 and STE 1971/6-1), and the Collaborative Research Center CRC 1371., We thank Harald Brüssow for critically reading the manuscript and Jorge Moura de Sousa for valuable discussion and opinion on early versions of the manuscript. We thank Dwayne Roach and Anne Chevallereau for valuable discussions. We thank Sean Benler for kindly sharing the comprehensive HMM database of Ig-like domains identified on Pfam database. We thank the members of the Centre for Gnotobiology Platform of the Institut Pasteur (Thierry Angélique, Eddie Maranghi, Martine Jacob, and Marisa Gabriela Lopez Dieguez) for their help with the animal work. We thank Cédric Fund for 16S libraries and sequencing from the Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09) and IBISA., Institut Pasteur [Paris] (IP), Collège Doctoral, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Cova Rodrigues, Ana
Subjects: Male, Phage therapy, enteroaggregative, medicine.medical_treatment, viruses, [SDV]Life Sciences [q-bio], murine intestine, Gut flora, medicine.disease_cause, gnotobiotic mice, Microbiology, Predation, 03 medical and health sciences, Feces, Mice, 0302 clinical medicine, Virology, medicine, Escherichia coli, microbiota, Animals, Germ-Free Life, Bacteriophages, mucosa, Ecosystem, intestinal microbes, 030304 developmental biology, 0303 health sciences, Mucous Membrane, Oligo mouse microbiota, biology, Bacteria, Ecological dynamics, gut biogeography, biology.organism_classification, Spatial heterogeneity, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Gastrointestinal Tract, Mice, Inbred C57BL, Models, Animal, Microbial Interactions, Parasitology, Female, 030217 neurology & neurosurgery
Abstract: International audience; The ecological dynamics underlying the coexistence between antagonistic populations of bacteria and their viruses, bacteriophages (phages), in the mammalian gut microbiota remain poorly understood. We challenged a murine synthetic bacterial community with phages to study the factors allowing phages-bacteria coexistence. Coexistence was not dependent on the development of phage-resistant clones nor on the ability of phages to extend their host range. Instead, our data suggest that phage-inaccessible sites in the mucosa serve as a spatial refuge for bacteria. From there, bacteria disseminate in the gut lumen where they are predated by luminal phages fostering the presence of intestinal phage populations. The heterogeneous biogeography of microbes contributes to the long-term coexistence of phages with phage-susceptible bacteria. This observation could explain the persistence of intestinal phages in humans as well as the low efficiency of oral phage therapy against enteric pathogens in animal models and clinical trials.
Published: 2020
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17. 'I will survive': A tale of bacteriophage-bacteria coevolution in the gut

Author: Laurent Debarbieux, Marta Lourenço, Luisa De Sordi, Département de Microbiologie - Department of Microbiology, Institut Pasteur [Paris] (IP), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Collège Doctoral, Sorbonne Université (SU), Institut Carnot Pasteur Maladie Infectieuse ANR-11-CARN-017-01, This project has received funding from DigestScience Foundation (Lille, France) and the Institut Carnot Pasteur Maladie Infectieuse (ANR 11-CARN 017-01)., Institut Pasteur [Paris], and Collège doctoral [Sorbonne universités]
Subjects: 0301 basic medicine, Microbiology (medical), Microbial diversity, gut ecology, phage-bacteria coevolution, Genomics, Microbiology, Defining/profiling gut microbiome, Models, Biological, Bacteriophage, Biological Coevolution, 03 medical and health sciences, 0302 clinical medicine, Antibiosis, microbiota, genomics, Animals, Humans, Bacteriophages, Genetic variability, Coevolution, biology, Bacteria, Gastroenterology, Genetic Variation, Bacterial populations, Biodiversity, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Adaptation, Physiological, Gut microbiome, Addendum, Gastrointestinal Microbiome, Intestines, 030104 developmental biology, Infectious Diseases, Evolutionary biology, microbial diversity, 030211 gastroenterology & hepatology, Intestinal bacteria, gastrointestinal tract
Abstract: International audience; Viruses that infect bacteria, or bacteriophages, are among the most abundant entities in the gut microbiome. However, their role and the mechanisms by which they infect bacteria in the intestinal tract remain poorly understood. We recently reported that intestinal bacteria are an evolutionary force, driving the expansion of the bacteriophage host range by boosting the genetic variability of these viruses. Here, we expand these observations by studying antagonistic bacteriophage-bacteria coevolution dynamics and revealing that bacterial genetic variability is also increased under the pressure of bacteriophage predation. We propose a model showing how the expansion of bacteriophage-bacteria infection networks is relative to the opportunities for coevolution encountered in the intestinal tract. Our data suggest that predator-prey dynamics are perpetuated and differentiated in parallel, to generate and maintain intestinal microbial diversity and equilibrium.
Published: 2018
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18. Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C-infected Egyptian cohort: A comparative analysis

Author: Shimaa Afify, Mohamed Salaheldin, Ahmad Sweedy, Naglaa Youssef, Arnaud Fontanet, A. El Tahan, Kévin Jean, G. Esmat, Mohamed Eltabbakh, Anna L. Funk, M. El Kassas, Yusuke Shimakawa, Helwan University [Caire], Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Université Ain Shams, Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Cairo University, National Hepatology and Tropical Medicine Research Institute [Cairo], Institut Carnot Pasteur Maladie Infectieuse ANR-11-CARN-017-01, The authors declare no personal conflict of interests. Anna Funk is part of the Pasteur‐Paris University (PPU) International PhD Program and has received funding from the Institut Carnot Pasteur Maladie Infectieuse (ANR 11‐CARN 017‐01). This work benefited from the kind contribution of Alice Zuccaire., Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)
Subjects: Male, Oncology, Rate ratio, MESH: Egypt, 0302 clinical medicine, MESH: Liver Neoplasms, Recurrence, Prospective Studies, hepatitis c, MESH: Carcinoma, Hepatocellular, Prospective cohort study, education.field_of_study, MESH: Middle Aged, Liver Neoplasms, hepatocellular carcinoma, Hepatitis C, Middle Aged, MESH: Hepatitis C, Chronic, 3. Good health, Infectious Diseases, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, symbols, Egypt, Female, 030211 gastroenterology & hepatology, Liver cancer, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, 03 medical and health sciences, symbols.namesake, Virology, Internal medicine, medicine, Humans, Poisson regression, education, MESH: Humans, Hepatology, business.industry, DAAs, Hepatitis C, Chronic, medicine.disease, MESH: Male, MESH: Prospective Studies, digestive system diseases, MESH: Recurrence, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: International audience; In Egypt, hepatocellular carcinoma (HCC) is the most common form of cancer and direct-acting antivirals (DAA) are administered on a large scale to patients with chronic HCV infection to reduce the risk. In this unique setting, we aimed to determine the association of DAA exposure with early-phase HCC recurrence in patients with a history of HCV-related liver cancer. This was a prospective cohort study of an HCV-infected population from one Egyptian specialized HCC management centre starting from the time of successful HCC intervention. The incidence rates of HCC recurrence between DAA-exposed and nonexposed patients were compared, starting from date of HCC complete radiological response and censoring after 2 years. DAA exposure was treated as time varying. Two Poisson regressions models were used to control for potential differences in the exposed and nonexposed group; multivariable adjustment and balancing using inverse probability of treatment weighting (IPTW). We included 116 patients: 53 treated with DAAs and 63 not treated with DAAs. There was 37.7% and 25.4% recurrence in each group after a median of 16.0 and 23.0 months of follow-up, respectively. Poisson regression using IPTW demonstrated an association between DAAs and HCC recurrence with an incidence rate ratio of 3.83 (95% CI: 2.02-7.25), which was similar in the multivariable-adjusted model and various sensitivity analyses. These results add important evidence towards the possible role of DAAs in HCC recurrence and stress the need for further mechanistic studies and clinical trials to accurately confirm this role and to identify patient characteristics that may be associated with this event.
Published: 2018
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19. How the structure, nutritional and sensory attributes of pasta made from legume flour is affected by the proportion of legume protein

Author: Pascal Schlich, Sylvie Cordelle, Stéphane Walrand, Cecile Barron, Karima Laleg, Valérie Micard, Ingénierie des Agro-polymères et Technologies Émergentes ( IATE ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Université de Montpellier ( UM ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut national d’études supérieures agronomiques de Montpellier ( Montpellier SupAgro ) -Institut National de la Recherche Agronomique ( INRA ) -Centre international d'études supérieures en sciences agronomiques ( Montpellier SupAgro ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Unité de Nutrition Humaine ( UNH ), Clermont Université-Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Institut National de la Recherche Agronomique ( INRA ), Qualiment Institut Carnot, Institut National de la Recherche Agronomique ( INRA ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Clermont Université, VEGAGE project (Qualiment Institut Carnot), Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Micard, Valérie, Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), and Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)
Subjects: protein network structure, cooking quality, in-vitro protein digestion, trypsin inhibitory activity, sensory analysis, propriété sensorielle, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, pea, Ingénierie des aliments, lentil, aliment enrichi, digestion in vitro, [SDV.IDA]Life Sciences [q-bio]/Food engineering, inhibitors, matrice protéique, Food science, In-vitro protein digestion, Trypsin inhibitory activity, Legume, 2. Zero hunger, chemistry.chemical_classification, [ SDV.IDA ] Life Sciences [q-bio]/Food engineering, food and beverages, 04 agricultural and veterinary sciences, Sensory analysis, Trypsin, Whole wheat, 040401 food science, trypsin, trypsine, Alimentation et Nutrition, Protein network, medicine.drug, Hydrolyzed protein, Protein digestion, propriété nutritionnelle, comportement à la cuisson, lupin flours, 0404 agricultural biotechnology, pâte alimentaire, medicine, Food engineering, Food and Nutrition, spaghetti, analyse sensorielle, dough, temperature, antinutritional factors, Gluten, chemistry, digestibility, Protein network structure, gluten, Food Science
Abstract: International audience; In this study, wheat in pasta was partially or completely replaced by faba to increase its protein quantity and improve its quality. Increasing the ratio of faba:wheat protein from 0:100 to 100:0 (gig) in pasta enlarged its protein network at the microscopic scale and linearly diluted the covalently linked gluten network of wheat pasta by weakly linked proteins. A concomitant linear increase in the cooking loss (up to 2.6 fold), a decrease in resilience (up to 1.4 fold) and an increase of the in-vitro protein digestion (up to 25%) were observed in pasta. The increase in drying temperature (90 degrees C vs. 55 degrees C) promoted the covalent aggregation of proteins in all pasta, but was more efficient in legume pasta, enhancing their resilience and reducing their cooking loss, without altering the degree of protein hydrolysis. This was partly explained by the reduction in trypsin inhibitory activity in all legume pasta dried at 90 degrees C. Interestingly, scores for sensory attributes such as liking attributed to pasta containing 80% faba-protein were close to scores given to a commercial whole wheat pasta. Pasta made exclusively from faba dried at 55 degrees C or 90 degrees C tended to be liked more than their commercial gluten-free counterparts.
Published: 2017
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20. Defective lytic transglycosylase disrupts cell morphogenesis by hindering cell wall de-O-acetylation in Neisseria meningitidis

Author: Joseph P. Dillard, Ahmed Haouz, Muhamed-Kheir Taha, William P. Robins, Christian Malosse, Ala-Eddine Deghmane, Julia Chamot-Rooke, Maryse Moya Nilges, Ryan E. Schaub, Ivo G. Boneca, Ignacio Santecchia, Richard J. Wheeler, Allison H. Williams, Samia Hicham, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Infections Bactériennes Invasives, Institut Pasteur [Paris], Université Paris Descartes - Paris 5 (UPD5), Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Cristallographie (Plateforme) - Crystallography (Platform), Harvard Medical School [Boston] (HMS), European Molecular Biology Organization (ALTF 732-2010), European Research Council (PGN from SHAPE to VIR 202283), Fondation pour la Recherche Médicale (DBF20160635726), Institut Carnot-Pasteur (Maladies Infectious fellowship), Institut Carnot Pasteur Microbes and Santé, Fondation pour la Recherche Médicale (FDT201805005258)AHW was supported by an EMBO long-term fellowship (ALTF 732–2010) and an Institut Carnot-Pasteur Maladies Infectious fellowship. This work was supported by an ERC starting grant (PGN from SHAPE to VIR 202283) and a Fondation pour la recherche médicale (FRM) grant Programme d’Urgence (DBF20160635726) to IGB. This study received funding from the French Government′s Investissement d′Avenir program, Laboratoire d′Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR- 10-LABX-62-IBEID). IS was supported by the Institut Carnot Pasteur Microbes and Santé given to the Pasteur-Paris University PhD program and the ‘Fin de these de science’ number FDT201805005258 granted by 'Fondation pour la recherche médicale (FRM). The UtechS Photonic BioImaging (Imagopole), C2RT, Institut Pasteur was supported by the French National Research Agency (France BioImaging, ANR-10–INSB–04, Investments for the Future)., We acknowledge the synchrotron beamline staff (PROXIMA-1 at SOLEIL and X06DA at SLS) for their assistance. We are extremely grateful to Frederick Saul, Patrick Weber and Marco Bellinzoni for their constant helpful guidance, advice and assistance. We thank Dr. Antoine Forget for the advice on and help with figure presentations., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, cell division, Cell division, QH301-705.5, Science, infectious disease, 030106 microbiology, Neisseria meningitidis, peptidoglycan, General Biochemistry, Genetics and Molecular Biology, Bacterial cell structure, Cell wall, Lytic transglycosylase, 03 medical and health sciences, chemistry.chemical_compound, Cell Wall, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Catalytic Domain, Morphogenesis, Amino Acid Sequence, Biology (General), X-ray crystallography, chemistry.chemical_classification, Microbiology and Infectious Disease, General Immunology and Microbiology, biology, Cell morphogenesis, General Neuroscience, microbiology, E. coli, Active site, Glycosyltransferases, General Medicine, Cell biology, 030104 developmental biology, Enzyme, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Lytic cycle, cell separation, biology.protein, Medicine, Peptidoglycan, Research Article, Protein Binding
Abstract: Lytic transglycosylases (LT) are enzymes involved in peptidoglycan (PG) remodeling. However, their contribution to cell-wall-modifying complexes and their potential as antimicrobial drug targets remains unclear. Here, we determined a high-resolution structure of the LT, an outer membrane lipoprotein from Neisseria species with a disordered active site helix (alpha helix 30). We show that deletion of the conserved alpha-helix 30 interferes with the integrity of the cell wall, disrupts cell division, cell separation, and impairs the fitness of the human pathogen Neisseria meningitidis during infection. Additionally, deletion of alpha-helix 30 results in hyperacetylated PG, suggesting this LtgA variant affects the function of the PG de-O-acetylase (Ape 1). Our study revealed that Ape 1 requires LtgA for optimal function, demonstrating that LTs can modulate the activity of their protein-binding partner. We show that targeting specific domains in LTs can be lethal, which opens the possibility that LTs are useful drug-targets., eLife digest Bacteria are surrounded by a tough yet flexible wall that protects the cell and serves as an anchor for several of the cell’s structures. This cell wall contains a large mesh-like molecule called peptidoglycan made of many repeated building blocks. When a bacterial cell divides in two, it needs to make more of this material. Making peptidoglycan involves two different sets of enzymes working together: “polymerases” are the enzymes that link the individual building blocks to peptidoglycan, one after the other; while “lytic transglycosylases” are enzymes that modify the peptidoglycan to create space for the addition of new building blocks and for assemblies of proteins that must span the cell wall. Lytic transglycosylases are known to assemble with other proteins and enzymes to form the cell’s peptidoglycan-modifying machinery, but it was not clear exactly what purpose they serve within these “enzyme complexes”. It was also unclear whether these enzymes would be good targets for new antibiotics. To help answer these questions, Williams et al. looked at a lytic transglycoslyase called LtgA. This enzyme is originally from Neisseria meningitidis, a bacterium that can cause meningitis and life-threatening sepsis in humans. Williams et al. discovered that part of the enzyme’s active site – the region of an enzyme where the chemical reaction takes – can switch from an ordered helix to a disordered, flexible loop. Bacteria were then genetically engineered to make a version of the enzyme that lacked this helix. These bacteria had weaker cell walls and were deformed; they were also less able to grow and divide, both in the laboratory and in a mouse model of infection. Further analysis showed that the deletion of the helix from the enzyme resulted in the peptidoglycan being modified much more than normal, which could likely explain their reduced virulence. Williams et al. also found that deleting the helix from LtgA interfered with the activity of a protein that interacts with this enzyme, called Ape1, which also contributed to the fragility of the cell wall. This shows that lytic transglycosylases assembled into enzyme complexes can alter the activities of other proteins in the complex. Together these findings show that researchers could target one enzyme in a complex in bacteria, and disrupt the activity of other proteins in that complex. This highlights the possibility of considering enzyme complexes as useful targets for new drugs, which is important considering the current problem of antibiotic resistance.
Published: 2020
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21. Diversity of mucoid to non-mucoid switch among carbapenemase-producing Klebsiella pneumoniae

Author: Philippe Glaser, Adriana Chiarelli, Rémy A. Bonnin, Nicolas Cabanel, Pengdbamba Dieudonné Zongo, Isabelle Rosinski-Chupin, Thierry Naas, Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Structure, Dynamique, Fonction Et Expression Des Beta-Lactamases À Large Spectre, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11)-Université Paris-Sud - Paris 11 (UP11)-Centre National de Référence de la Résistance aux Antibiotiques (CNR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), This work was supported by grants from the French National Research Agency (ANR-10-LABX-62-IBEID and ANR-10-LABX-33), and from the European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No. 773830 (Project MedVetKlebs, One Health EJP). Adriana Chiarelli is part of the Pasteur - Paris University (PPU) International PhD Program. This project has received funding from the Institut Carnot Pasteur Microbes & Santé, and the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 665807., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health)(2018), European Project: 773830, H2020-SFS-2017-1 ,One Health EJP(2018), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and Adriana Chiarelli is part of the Pasteur - Paris University (PPU) International PhD Program.This project has received funding from the Institut Carnot Pasteur Microbes & Santé, and the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 665807
Subjects: Carbapenem, Klebsiella pneumoniae, MESH: Klebsiella pneumoniae, lcsh:QR1-502, MESH: beta-Lactamases, MESH: Virulence, Virulence factor, lcsh:Microbiology, MESH: Carbapenems, Drug Resistance, Multiple, Bacterial, Insertion sequence, MESH: Bacterial Proteins, Capsule, 0303 health sciences, MESH: Microbial Sensitivity Tests, MESH: Gene Expression Regulation, Bacterial, Virulence, Biofilm, Phenotype, MESH: Capsule, Carbapenem, Insertion sequence, Biofilm, Klebsiella pneumoniae, Anti-Bacterial Agents, 3. Good health, MESH: Klebsiella Infections, MESH: Genes, Bacterial, Research Article, medicine.drug, Microbiology (medical), Virulence Factors, Locus (genetics), Microbial Sensitivity Tests, MESH: Biofilms, Biology, MESH: Phenotype, Microbiology, beta-Lactamases, 03 medical and health sciences, Bacterial Proteins, MESH: Anti-Bacterial Agents, MESH: Bacterial Capsules, medicine, Animals, Humans, Gene, Bacterial Capsules, 030304 developmental biology, MESH: Virulence Factors, MESH: Humans, Colistin, 030306 microbiology, Gene Expression Regulation, Bacterial, MESH: Drug Resistance, Multiple, Bacterial, MESH: Colistin, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Klebsiella Infections, Carbapenems, Genes, Bacterial, Biofilms
Abstract: Background Klebsiella pneumoniae is a leading cause of intractable hospital-acquired multidrug-resistant infections and carbapenemase-producing K. pneumoniae (CPKp) are particularly feared. Most of the clinical isolates produce capsule as a major virulence factor. Recombination events at the capsule locus are frequent and responsible for capsule diversity within Klebsiella spp. Capsule diversity may also occur within clonal bacterial populations generating differences in colony aspect. However, little is known about this phenomenon of phenotypic variation in CPKp and its consequences. Results Here, we explored the genetic causes of in vitro switching from capsulated, mucoid to non-mucoid, non-capsulated phenotype in eight clinical CPKp isolates. We compared capsulated, mucoid colony variants with one of their non-capsulated, non-mucoid isogenic variant. The two colony variants were distinguished by their appearance on solid medium. Whole genome comparison was used to infer mutations causing phenotypic differences. The frequency of phenotypic switch was strain-dependent and increased along with colony development on plate. We observed, for 72 non-capsulated variants that the loss of the mucoid phenotype correlates with capsule deficiency and diverse genetic events, including transposition of insertion sequences or point mutations, affecting genes belonging to the capsule operon. Reduced or loss of capsular production was associated with various in vitro phenotypic changes, affecting susceptibility to carbapenem but not to colistin, in vitro biofilm formation and autoaggregation. Conclusions The different impact of the phenotypic variation among the eight isolates in terms of capsule content, biofilm production and carbapenem susceptibility suggested heterogeneous selective advantage for capsular loss according to the strain and the mutation. Based on our results, we believe that attention should be paid in the phenotypic characterization of CPKp clinical isolates, particularly of traits related to virulence and carbapenem resistance.
Published: 2020
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22. Gene alterations in epigenetic modifiers and JAK-STAT signaling are frequent in breast implant-associated ALCL

Author: Luc Xerri, Alina Nicolae, Reda Bouabdallah, Joan Somja, Marie-Pierre Chenard, François-Xavier Frenois, Fabien Reyal, Catherine Chassagne-Clément, Lénaïg Mescam, Marie-Hélène Delfau-Larue, Frédéric Escudié, Anne Moreau, Corinne Haioun, Philippe Gaulard, Lucie Oberic, Nadia Amara, Asma Beldi-Ferchiou, Laetitia Lacroix, Alexandra Traverse-Glehen, François Lemonnier, Jean-Marc Schiano, Bruno Tesson, Virginie Fataccioli, Marie Bannier, Daniel Birnbaum, Cécile Laurent, Nadine Martin, P. Brousset, Fabien Le Bras, José Adélaïde, Marc André, Naïs Prade, Camille Laurent, Arnaud Guille, Anne-Sophie Hamy, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Bidaut, Ghislain, Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Rt2 Lab, Institut Curie [Paris], CHU Henri Mondor, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Islamic University of Gaza (IUG - IU Gaza), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Carnot Lymphome (CALYM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie Pathologique Générale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'anatomopathologie, biopathologie, Centre Léon Bérard [Lyon], Groupe de Recherche d'Histoire (GRHis), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Études des Phénomènes Aléatoires et Géophysiques (CEPHAG), École Nationale Supérieure d'Ingénieurs Électriciens de Grenoble (ENSIEG)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre des maladies du sein, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Surgery Department, CRLCC Paul Strauss, Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Henri Mondor, Service d'Hématologie, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IUCT Oncopole - Institut Universitaire du Cancer de Toulouse, UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Service d'Hématologie [CHU Toulouse], CHU Toulouse [Toulouse], Laboratoire d'Hématologie [Purpan], CHU Henri Mondor [Créteil], École Pratique des Hautes Études (EPHE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut Carnot CALYM [Pierre-Benite], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]
Subjects: Adult, 0301 basic medicine, DNA Copy Number Variations, Breast Implants, [SDV]Life Sciences [q-bio], Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, medicine.disease_cause, Biochemistry, Germline, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Epigenetics, SOCS3, STAT3, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Anaplastic large-cell lymphoma, PI3K/AKT/mTOR pathway, ComputingMilieux_MISCELLANEOUS, Aged, Janus Kinases, Aged, 80 and over, Mutation, Lymphoid Neoplasia, Genome, Human, JAK-STAT signaling pathway, Cell Biology, Hematology, Middle Aged, medicine.disease, [SDV] Life Sciences [q-bio], STAT Transcription Factors, 030104 developmental biology, Cancer research, biology.protein, Lymphoma, Large-Cell, Anaplastic, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Signal Transduction, 030215 immunology
Abstract: The oncogenic events involved in breast implant-associated anaplastic large cell lymphoma (BI-ALCL) remain elusive. To clarify this point, we have characterized the genomic landscape of 34 BI-ALCLs (15 tumor and 19 in situ subtypes) collected from 54 BI-ALCL patients diagnosed through the French Lymphopath network. Whole-exome sequencing (n = 22, with paired tumor/germline DNA) and/or targeted deep sequencing (n = 24) showed recurrent mutations of epigenetic modifiers in 74% of cases, involving notably KMT2C (26%), KMT2D (9%), CHD2 (15%), and CREBBP (15%). KMT2D and KMT2C mutations correlated with a loss of H3K4 mono- and trimethylation by immunohistochemistry. Twenty cases (59%) showed mutations in ≥1 member of the JAK/STAT pathway, including STAT3 (38%), JAK1 (18%), and STAT5B (3%), and in negative regulators, including SOCS3 (6%), SOCS1 (3%), and PTPN1 (3%). These mutations were more frequent in tumor-type samples than in situ samples (P = .038). All BI-ALCLs expressed pSTAT3, regardless of the mutational status of genes in the JAK/STAT pathway. Mutations in the EOMES gene (12%) involved in lymphocyte development, PI3K-AKT/mTOR (6%), and loss-of-function mutations in TP53 (12%) were also identified. Copy-number aberration (CNA) analysis identified recurrent alterations, including gains on chromosomes 2, 9p, 12p, and 21 and losses on 4q, 8p, 15, 16, and 20. Regions of CNA encompassed genes involved in the JAK/STAT pathway and epigenetic regulators. Our results show that the BI-ALCL genomic landscape is characterized by not only JAK/STAT activating mutations but also loss-of-function alterations of epigenetic modifiers.
Published: 2019
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23. Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes

Author: Frédéric Martins, Sarah Cadot, Carine Valle, Mary Poupot, Marie Tosolini, Anne Quillet-Mary, Francesco Dieli, Camille Laurent, Serena Meraviglia, Jean-Jacques Fournié, Pierre Milpied, Gabriele Pizzolato, Delphine Labourdette, Julie Déchanet-Merville, Don-Marc Franchini, Hannah Kaminski, Loic Ysebaert, Frédéric Pont, Pierre Merville, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Immunologie et Cancérologie Intégrative, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Laboratoire de Génétique Cellulaire (LGC), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biopathology and Medical Biotechnologies, University of Palermo, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Immunologie et Cancérologie Intégratives (CRC - Inserm U1138), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Pizzolato, Gabriele, Kaminski, Hannah, Tosolini, Marie, Franchini, Don-Marc, Pont, Fréderic, Martins, Fréderic, Valle, Carine, Labourdette, Delphine, Cadot, Sarah, Quillet-Mary, Anne, Poupot, Mary, Laurent, Camille, Ysebaert, Loic, Meraviglia, Serena, Dieli, Francesco, Merville, Pierre, Milpied, Pierre, Déchanet-Merville, Julie, Fournié, Jean-Jacques, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), ERL 5294, Centre National de la Recherche Scientifique (CNRS), Programme Hospitalo, Universitaire en Cancérologie (CAPTOR), Institut Carnot Lymphome (CALYM), Humanitas University, Università degli studi di Palermo - University of Palermo, Central Laboratory of Advanced Diagnosis and Biomedical Research, Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie et Transplantation Rénale, Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Sante et de la Recherche Medicale (Inserm), Universite Toulouse III: Paul Sabatier, Laboratoire d'Excellence Toulouse Cancer [ANR11-LABX], Programme Hospitalo-Universitaire en Cancerologie CAPTOR [ANR11-PHUC0001], SIRIC Bordeaux Research in Oncology, Ligue nationale contre le cancer, Fondation pour la Recherche Medicale, ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), Université de Toulouse, Institut Carnot Lymphome CALYM, CNRS, ImmunoConcEpT, UMR 5164, Université de Bordeaux, PlateformeGeT, Genotoul, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), ProdInra, Archive Ouverte, and Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Lymphocyte, [SDV]Life Sciences [q-bio], CD8-Positive T-Lymphocytes, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Transcriptome, 0302 clinical medicine, T-Lymphocyte Subsets, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cytotoxic T cell, single-cell RNA-sequencing, Cells, Cultured, T-lymphocytes, ComputingMilieux_MISCELLANEOUS, Cancer, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, gamma delta T lymphocyte, Receptors, Antigen, T-Cell, gamma-delta, Cell biology, Killer Cells, Natural, medicine.anatomical_structure, PNAS Plus, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, γδ T lymphocyte, expression des gènes, Adult, T cell, Biology, lymphocyte, Peripheral blood mononuclear cell, 03 medical and health sciences, Antigen, séquençage arnr 16s, medicine, Humans, Cell Proliferation, 030304 developmental biology, human immunology, Base Sequence, Sequence Analysis, RNA, T-cell receptor, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Leukocytes, Mononuclear, Immunologic Memory, transcriptome, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: γδ T lymphocytes represent ∼1% of human peripheral blood mononuclear cells and even more cells in most tissues of vertebrates. Although they have important anticancer functions, most current single-cell RNA sequencing (scRNA-seq) studies do not identify γδ T lymphocytes because their transcriptomes at the single-cell level are unknown. Here we show that high-resolution clustering of large scRNA-seq datasets and a combination of gene signatures allow the specific detection of human γδ T lymphocytes and identification of their T cell receptor (TCR)Vδ1 and TCRVδ2 subsets in large datasets from complex cell mixtures. In t -distributed stochastic neighbor embedding plots from blood and tumor samples, the few γδ T lymphocytes appear collectively embedded between cytotoxic CD8 T and NK cells. Their TCRVδ1 and TCRVδ2 subsets form close yet distinct subclusters, respectively neighboring NK and CD8 T cells because of expression of shared and distinct cytotoxic maturation genes. Similar pseudotime maturation trajectories of TCRVδ1 and TCRVδ2 γδ T lymphocytes were discovered, unveiling in both subsets an unattended pool of terminally differentiated effector memory cells with preserved proliferative capacity, a finding confirmed by in vitro proliferation assays. Overall, the single-cell transcriptomes of thousands of individual γδ T lymphocytes from different CMV + and CMV − donors reflect cytotoxic maturation stages driven by the immunological history of donors. This landmark study establishes the rationale for identification, subtyping, and deep characterization of human γδ T lymphocytes in further scRNA-seq studies of complex tissues in physiological and disease conditions.
Published: 2019
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24. Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum. Long text of the Joint French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa. Part 1 Diagnostic exploration and staging, surgery, perioperative care, and pathology

Author: Laurence Gladieff, Blandine Courbiere, Christine Rousset-Jablonski, Cyrille Huchon, Fabrice Lecuru, I.L. Ray-Coquard, Laure Fournier, Mojgan Devouassoux-Shisheboran, Chantal Touboul, Eric Lambaudie, Isabelle Thomassin-Naggara, Sebastien Gouy, Marie-Aude Lefrère-Belda, G. Ferron, Eric Leblanc, Benoit You, L. Ouldamer, V. Lavoué, C. Bourgin, Alexandra Leary, A. Lemoine, Francis Bonnet, C. Sénéchal-Davin, Emile Daraï, P. Collinet, Fabrice Narducci, P. Alfonsi, Naoual Bakrin, Marcos Ballester, Catherine Uzan, T. de la Motte Rouge, François Golfier, Nathalie Chabbert-Buffet, Pierre-Adrien Bolze, Cherif Akladios, Nicolas Pouget, Patricia Pautier, F Guyon, Claire Falandry, Sofiane Bendifallah, François Planchamp, Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Centre Eugène Marquis (CRLCC), Institut Claudius Regaud, Département de chirurgie gynécologique [Gustave Roussy], Institut Gustave Roussy (IGR), Institut Bergonié [Bordeaux], UNICANCER, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Oncologie gynécologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut Curie [Paris], Centre Léon Bérard [Lyon], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Carnot CALYM [Pierre-Benite], Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lille-UNICANCER, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Institut Carnot Lymphome (CALYM)
Subjects: Thorax, medicine.medical_specialty, medicine.medical_treatment, Ovary, [SDV.CAN]Life Sciences [q-bio]/Cancer, Guidelines, Perioperative Care, 03 medical and health sciences, 0302 clinical medicine, Ovarian cancer, Biomarkers, Tumor, Fallopian Tube Neoplasms, Humans, Minimally Invasive Surgical Procedures, Medicine, Chemotherapy, Neoplasms, Glandular and Epithelial, Neoplasm Metastasis, Peritoneal Neoplasms, Pelvis, Neoplasm Staging, Ovarian Neoplasms, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics and Gynecology, medicine.disease, Primary peritoneal cancer, Magnetic Resonance Imaging, 3. Good health, Surgery, Omentectomy, medicine.anatomical_structure, Reproductive Medicine, Tubal cancer, 030220 oncology & carcinogenesis, Abdomen, Female, Laparoscopy, France, Tomography, X-Ray Computed, business, Fallopian tube
Abstract: International audience; An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B).
Published: 2019
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25. Fungal mediated innate immune memory, what have we learned?

Author: Jessica Quintin, Immunologie des Infections fongiques - immunology of fungal infections, Institut Pasteur [Paris], Institut Carnot Pasteur Maladie Infectieuse ANR-11-CARN-017-01, This work was supported by the ANR JCJC grant [ANR-16-CE15-0014-01] and the Institut Carnot Pasteur MI grant [ANR 11-CARN 017-01] (to J.Q.)., ANR-16-CE15-0014,IIMory,Mémoire immunologique innée des défenses de l'hôte(2016), and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, animal diseases, [SDV]Life Sciences [q-bio], Context (language use), chemical and pharmacologic phenomena, β-glucan, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Fungal Components, Immunological memory, MESH: Monocytes, Monocytes, 03 medical and health sciences, Innate immune memory, 0302 clinical medicine, MESH: Mycoses, Immunity, Candida albicans, Humans, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Immune status, Innate immune system, MESH: Humans, biology, Macrophages, MESH: Candida albicans, Fungi, MESH: Macrophages, Cell Biology, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Immunity, Innate, 3. Good health, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Mycoses, Immunology, MESH: Immunologic Memory, bacteria, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, Immunologic Memory, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; The binary classification of mammalian immune memory is now obsolete. Innate immune cells carry memory characteristics. The overall capacity of innate immune cells to remember and alter their responses is referred as innate immune memory and the induction of a non-specific memory resulting in an enhanced immune status is termed "trained immunity". Historically, trained immunity was first described as triggered by the human fungal pathogen Candida albicans. Since, numerous studies have accumulated and deciphered the main characteristics of trained immunity mediated by fungi and fungal components. This review aims at presenting the newly described aspect of memory in innate immunity with an emphasis on the historically fungal mediated one, covering the known molecular mechanisms associated with training. In addition, the review uncovers the numerous non-specific effect that β-glucans trigger in the context of infectious diseases and septicaemia, inflammatory diseases and cancer.
Published: 2019
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26. The Battle Within: Interactions of Bacteriophages and Bacteria in the Gastrointestinal Tract

Author: Luisa De Sordi, Laurent Debarbieux, Marta Lourenço, Département de Microbiologie - Department of Microbiology, Institut Pasteur [Paris], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Institut Carnot Pasteur Maladie Infectieuse ANR-11-CARN-017-01, M.L. is part of the Pasteur- Paris University (PPU) International PhD Program and has received funding from the Institut Carnot Pasteur Maladie Infectieuse (ANR 11-CARN 017- 01). L.D.S. is funded by a Roux-Cantarini fellowship from the Institut Pasteur (Paris, France). L.D. received support from the DigestScience Foundation (Lille, France)., Cova Rodrigues, Ana, Institut Pasteur [Paris] (IP), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Collège Doctoral
Subjects: [SDV]Life Sciences [q-bio], Intestinal physiology, In silico, Microbiology, MESH: Gastrointestinal Microbiome, Biological Coevolution, 03 medical and health sciences, Human health, Mice, 0302 clinical medicine, Virology, MESH: Biological Coevolution, Animals, Humans, MESH: Animals, Bacteriophages, MESH: Bacteriophages, MESH: Mice, Coevolution, 030304 developmental biology, Genetics, 0303 health sciences, Gastrointestinal tract, MESH: Humans, biology, Bacteria, Healthy subjects, biology.organism_classification, Gastrointestinal Microbiome, Specific Pathogen-Free Organisms, [SDV] Life Sciences [q-bio], MESH: Microbial Interactions, MESH: Specific Pathogen-Free Organisms, Gastrointestinal Tract, MESH: Bacteria, Microbial Interactions, MESH: Gastrointestinal Tract, Parasitology, 030217 neurology & neurosurgery
Abstract: International audience; The intestinal microbiota is intimately linked to human health. Decoding the mechanisms underlying its stability in healthy subjects should uncover causes of microbiota-associated diseases and pave the way for treatment. Bacteria and bacteriophages (phages) are the most abundant biological entities in the gastrointestinal tract, where their coexistence is dynamic and affixed. Phages drive and maintain bacterial diversity by perpetuating the coevolutionary interactions with their microbial prey. This review brings together recent in silico, in vitro, and in vivo work dissecting the complexity of phage-bacteria interactions in the intestinal microbiota, including coevolution perspectives. We define the types of dynamics encountered in the gastrointestinal tract and the parameters that affect their outcome. The impact of intestinal physiology on phagebacterial coevolution is analyzed in the light of its potential contribution to the relationship between the microbiota and human health.
Published: 2019
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27. miR-497 suppresses cycle progression through an axis involving CDK6 in ALK-positive cells

Author: Annabelle Congras, Fabienne Meggetto, Coralie Hoareau-Aveilla, Laurence Lamant, Delphine Labourdette, Nina Caillet, Cathy Quelen, Christine Dozier, Pierre Brousset, Laboratoire de biologie moléculaire eucaryote (LBME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomie et cytologie pathologiques [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Meggetto, Fabienne, Centre Hospitalier Universitaire de Toulouse, Institut Carnot ‘CALYM’ [Toulouse], Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ligue nationale contre le cancer, Fondation ARC pour la Recherche sur le Cancer', Institut National du Cancer (INCA) France, Labex TOUCAN/Laboratoire d'excellence Toulouse Cancer', Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Institut Carnot Lymphome (CALYM)
Subjects: [SDV]Life Sciences [q-bio], Apoptosis, Aggressive Non-Hodgkin's Lymphoma, medicine.disease_cause, Mice, 0302 clinical medicine, hemic and lymphatic diseases, Anaplastic lymphoma kinase, Medicine, Anaplastic Lymphoma Kinase, Lymphocytes, biology, microRNA, integumentary system, Cell Cycle, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Cell cycle, Cell Therapy and Immunotherapy, 3. Good health, Gene Expression Regulation, Neoplastic, Multigene Family, Heterografts, Lymphoma, Large-Cell, Anaplastic, Female, Signal Transduction, lymphome, Non-Hodgkin Lymphoma, CDK6 therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Palbociclib, Models, Biological, Article, 03 medical and health sciences, Cell Line, Tumor, cancer, Animals, Humans, Cell Proliferation, business.industry, Large cell, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Cyclin-Dependent Kinase 6, DNA Methylation, medicine.disease, Lymphoma, MicroRNAs, biology.protein, Cancer research, Ectopic expression, Cyclin-dependent kinase 6, business, Carcinogenesis, 030215 immunology, chimiorésistance
Abstract: International audience; Anaplastic large-cell lymphoma, a T-cell neoplasm, is primarily a pediatric disease. Seventy-five percent of pediatric anaplastic large-cell lymphoma cases harbor the chromosomal translocation t(2;5)(p23;q35) leading to the ectopic expression of NPM-ALK, a chimeric tyrosine kinase. NPM-ALK consists of an N-terminal nucleophosmin (NPM) domain fused to an anaplastic lymphoma kinase (ALK) cytoplasmic domain. Pediatric NPM-ALK+ anaplastic large-cell lymphoma is often a disseminated disease and young patients are prone to chemoresistance or relapse shortly after chemotherapeutic treatment. Furthermore, there is no gold standard protocol for the treatment of relapses. To the best of our knowledge, this is the first study on the potential role of the microRNA, miR-497, in NPM-ALK+ anaplastic large-cell lymphoma tumorigenesis. Our results show that miR-497 expression is repressed in NPM-ALK+ cell lines and patient samples through the hypermethylation of its promoter and the activity of NPM-ALK is responsible for this epigenetic repression. We demonstrate that overexpression of miR-497 in human NPM-ALK+ anaplastic large-cell lymphoma cells inhibits cellular growth and causes cell cycle arrest by targeting CDK6, E2F3 and CCNE1, the three regulators of the G1 phase of the cell cycle. Interestingly, we show that a scoring system based on CDK6, E2F3 and CCNE1 expression could help to identify relapsing pediatric patients. In addition, we demonstrate the sensitivity of NPM-ALK+ cells to CDK4/6 inhibition using for the first time a selective inhibitor, palbociclib. Together, our findings suggest that CDK6 could be a therapeutic target for the development of future treatments for NPM-ALK+ anaplastic large-cell lymphoma.
Published: 2019
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28. Microtubule-Driven Stress Granule Dynamics Regulate Inhibitory Immune Checkpoint Expression in T Cells

Author: Franchini, Don-Marc, Lanvin, Olivia, Tosolini, Marie, Patras de Campaigno, Emilie, Cammas, Anne, Pericart, Sarah, Scarlata, Clara-Maria, Lebras, Morgane, Rossi, Cédric, Ligat, Laetitia, Pont, Frédéric, Arimondo, Paola, Laurent, Camille, Ayyoub, Maha, Despas, Fabien, Lapeyre-Mestre, Maryse, Millevoi, Stefania, Fournié, Jean-Jacques, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Cancérologie Intégratives (CRC - Inserm U1138), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Equipe 11-E.Moyal/C.Toulas, Surfaces Cellulaires et Signalisation chez les Végétaux (SCSV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service d'hématologie, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Immunologie et Cancérologie Intégrative, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), CRLCC Paul Papin-CRLCC René Gauducheau, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées, Laboratoire d’Excellence ‘TOUCAN’ [Toulouse], Programme Hospitalo-Universitaire en Cancérologie CAPTOR [Cancer Pharmacology of Toulouse and Region] (IUCT Oncopole), IUCT Oncopole - Institut Universitaire du Cancer de Toulouse, Institut Carnot CALYM [Pierre-Benite], CHU Toulouse [Toulouse], INSERM, U1027, Toulouse, France., Centre d'investigation clinique de Toulouse (CIC 1436), Pharmacochimie de la Régulation Epigénétique du Cancer (ETaC), PIERRE FABRE-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This work was supported in part by institutional grants from INSERM, the Université Toulouse III - Paul Sabatier, the CNRS, the Programme Hospitalo-Universitaire en Cancérologie CAPTOR (ANR11-PHUC0001), the Laboratoire d’Excellence TOUCAN (ANR11-LABX), the Institut Universitaire du Cancer de Toulouse-Oncopole (CIEL), and the Institut Carnot Lymphome (CALYM)., ANR-11-LABX-0068,TOUCAN,Analyse intégrée de la résistance dans les cancers hématologiques(2011), and École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: stress granules, MESH: Humans, MESH: Immunotherapy, MESH: Microtubules, T-Lymphocytes, mRNA, [SDV]Life Sciences [q-bio], T cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, immune checkpoints, kinesin, microtubules, MESH: T-Lymphocytes, PD-1, Humans, [CHIM]Chemical Sciences, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunotherapy, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Despite the clinical success of blocking inhibitory immune checkpoint receptors such as programmed cell death-1 (PD-1) in cancer, the mechanisms controlling the expression of these receptors have not been fully elucidated. Here, we identify a post-transcriptional mechanism regulating PD-1 expression in T cells. Upon activation, the PDCD1 mRNA and ribonucleoprotein complexes coalesce into stress granules that require microtubules and the kinesin 1 molecular motor to proceed to translation. Hence, PD-1 expression is highly sensitive to microtubule or stress granule inhibitors targeting this pathway. Evidence from healthy donors and cancer patients reveals a common regulation for the translation of CTLA4, LAG3, TIM3, TIGIT, and BTLA but not of the stimulatory co-receptors OX40, GITR, and 4-1BB mRNAs. In patients, disproportionality analysis of immune-related adverse events for currently used microtubule drugs unveils a significantly higher risk of autoimmunity. Our findings reveal a fundamental mechanism of immunoregulation with great importance in cancer immunotherapy.
Published: 2019
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29. Human germinal center transcriptional programs are de-synchronized in B cell lymphoma

Author: Gabriel Brisou, Alexandra Traverse-Glehen, Bertrand Nadel, Bruno Tesson, Gilles Salles, Pierre Milpied, Marie-Laure Mollichella, Inaki Cervera-Marzal, Lionel Spinelli, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut Carnot CALYM [Pierre-Benite], Hospices Civils de Lyon (HCL), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut Carnot Lymphome (CALYM)
Subjects: Adult, Male, 0301 basic medicine, Lymphoma, B-Cell, Cellular differentiation, Immunology, B-Lymphocyte Subsets, Immunoglobulin Variable Region, Follicular lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 03 medical and health sciences, 0302 clinical medicine, Single-cell analysis, hemic and lymphatic diseases, medicine, Humans, Immunology and Allergy, B-cell lymphoma, Cells, Cultured, B cell, B-Lymphocytes, biology, Germinal center, Cell Differentiation, Middle Aged, Germinal Center, medicine.disease, Molecular biology, Lymphoma, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Single-Cell Analysis, Antibody, Transcriptome
Abstract: International audience; Most adult B cell lymphomas originate from germinal center (GC) B cells, but it is unclear to what extent B cells in overt lymphoma retain the functional dynamics of GC B cells or are blocked at a particular stage of the GC reaction. Here we used integrative single-cell analysis of phenotype, gene expression and variable-region sequence of the immunoglobulin heavy-chain locus to track the characteristic human GC B cell program in follicular lymphoma B cells. By modeling the cyclic continuum of GC B cell transitional states, we identified characteristic patterns of synchronously expressed gene clusters. GC-specific gene-expression synchrony was lost in single lymphoma B cells. However, distinct follicular lymphoma-specific cell states co-existed within single patient biopsies. Our data show that lymphoma B cells are not blocked in a GC B cell state but might adopt new dynamic modes of functional diversity, which opens the possibility of novel definitions of lymphoma identity.
Published: 2018
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30. The Complexity of Fungal β-Glucan in Health and Disease: Effects on the Mononuclear Phagocyte System

Author: Guillaume Tabouret, Giorgio Camilli, Jessica Quintin, Immunologie des Infections fongiques - immunology of fungal infections, Institut Pasteur [Paris], Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut Carnot Pasteur Maladie Infectieuse ANR-11-CARN-017-01, GC and JQ were supported by the ANR JCJC grant ANR-16-CE15-0014-01 (to JQ). GT and JQ were supported by the Institut Carnot Pasteur MI and Institut Carnot Animal Health (F2E) grant ANR 11-CARN 017-01., ANR-16-CE15-0014,IIMory,Mémoire immunologique innée des défenses de l'hôte(2016), Institut Pasteur [Paris] (IP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: lcsh:Immunologic diseases. Allergy, 0301 basic medicine, disease, fungal, health, mononuclear, phagocyte, β-glucan, Cell type, beta-Glucans, Phagocyte, Cell, Immunology, Mycology, Review, Biology, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunologie, medicine, Immunology and Allergy, Cytotoxic T cell, Animals, Humans, Receptor, Mononuclear Phagocyte System, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Innate immune system, Fungal Polysaccharides, Mononuclear phagocyte system, 3. Good health, Mycologie, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:RC581-607
Abstract: International audience; β-glucan, the most abundant fungal cell wall polysaccharide, has gained much attention from the scientific community in the last few decades for its fascinating but not yet fully understood immunobiology. Study of this molecule has been motivated by its importance as a pathogen-associated molecular pattern upon fungal infection as well as by its promising clinical utility as biological response modifier for the treatment of cancer and infectious diseases. Its immune effect is attributed to the ability to bind to different receptors expressed on the cell surface of phagocytic and cytotoxic innate immune cells, including monocytes, macrophages, neutrophils, and natural killer cells. The characteristics of the immune responses generated depend on the cell types and receptors involved. Size and biochemical composition of β-glucans isolated from different sources affect their immunomodulatory properties. The variety of studies using crude extracts of fungal cell wall rather than purified β-glucans renders data difficult to interpret. A better understanding of the mechanisms of purified fungal β-glucan recognition, downstream signaling pathways, and subsequent immune regulation activated, is, therefore, essential not only to develop new antifungal therapy but also to evaluate β-glucan as a putative anti-infective and antitumor mediator. Here, we briefly review the complexity of interactions between fungal β-glucans and mononuclear phagocytes during fungal infections. Furthermore, we discuss and present available studies suggesting how different fungal β-glucans exhibit antitumor and antimicrobial activities by modulating the biologic responses of mononuclear phagocytes, which make them potential candidates as therapeutic agents.
Published: 2018
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31. Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P-Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author: Thierry Jo Molina, Fabrice Jardin, Marc André, Richard Delarue, Sylvain Mareschal, Philippe Bertrand, Thierry Fest, Corinne Haioun, Pierre-Julien Viailly, Martin Figeac, Philippe Ruminy, Dominique Penther, Vinciane Marchand, Sydney Dubois, Frederic Peyrade, Jean-Michel Picquenot, Karen Leroy, Jean-Philippe Jais, Christiane Copie-Bergman, Bruno Tesson, Catherine Maingonnat, Bettina Fabiani, Elodie Bohers, Fabienne Desmots, Hervé Tilly, Nicolas Ketterer, Thierry Lamy, Pauline Peyrouze, Gilles Salles, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Res Ctr, Institut Curie, Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Lille 2 - Faculté de Médecine, Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement français du sang [Rennes] (EFS Bretagne), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d’immunologie, de thérapie cellulaire et d’hématopoïèse, Hôpital Pontchaillou, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pathologie [Mondor], Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Cliniques Universitaires UCL Mont-Godinne, Department of Oncology, Lausanne Hospital, Lausanne Hospital, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique [CHU Necker], Service d'informatique médicale et biostatistiques [CHU Necker], Institut Carnot Lymphome (CALYM), Faculté de Médecine Henri Warembourg - Université de Lille, Interactions cellulaires et moléculaires (ICM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Microenvironnement et cancer (MiCa), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Anatomie et cytologie pathologiques [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Pathologie [CHU Necker], Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes ( LITIS ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Institut national des sciences appliquées Rouen Normandie ( INSA Rouen Normandie ), Normandie Université ( NU ), HEMATOLOGIE, CRLCC Henri Becquerel, Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Dept Translat Res, Breast Canc Biol Grp, Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Institut pour la recherche sur le cancer de Lille [Lille] ( IRCL ) -Université de Lille, Droit et Santé, Microenvironment, Cell Differentiation, Immunology and Cancer ( MICMAC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement français du sang [Rennes] ( EFS Bretagne ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Carnot CALYM [Pierre-Benite], Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Université Côte d'Azur (UCA)-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-IFR140-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Sorbonne Université (SU)-CHU Saint-Antoine [APHP], Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU), MINES ParisTech - École nationale supérieure des mines de Paris, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Oncology, 0301 basic medicine, Cancer Research, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Bioinformatics, medicine.disease_cause, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Targeted therapy, 0302 clinical medicine, CDKN2A, hemic and lymphatic diseases, Copy-number variation, Aged, 80 and over, Genetics, 0303 health sciences, Mutation, NF-kappa B, High-Throughput Nucleotide Sequencing, hemic and immune systems, Genomics, Hematology, Middle Aged, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Female, Lymphoma, Large B-Cell, Diffuse, Signal Transduction, Adult, medicine.medical_specialty, Adolescent, DNA Copy Number Variations, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Genetic Heterogeneity, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, 030304 developmental biology, Genome, Human, Genetic heterogeneity, Germinal center, Cancer, Cell Biology, CD79B, medicine.disease, Lymphoma, Gene expression profiling, 030104 developmental biology, Myeloid Differentiation Factor 88, Diffuse large B-cell lymphoma, 030215 immunology
Abstract: Introduction: MYD88 mutations, notably the recurrent gain-of-function L265P variant, are a distinguishing feature of Activated B-Cell like (ABC) Diffuse Large B Cell Lymphoma (DLBCL), leading to constitutive NFkB pathway activation. The frequency of MYD88 mutations in DLBCL and other hematologic malignancies is well described; however, there has not yet been a large-scale study of a MYD88 mutated patient cohort with additional Next Generation Sequencing (NGS), copy number variation (CNV), and gene expression data, in order to thoroughly characterize the associated genomic profiles of these patients. The aims of our study were to compare the L265P and non-L265P mutations in terms of pathological and genetic features, to better detail the genomic background associated with MYD88 mutations in order to delineate patients potentially sensitive to targeted therapies, and to define the prognostic value of MYD88 mutations according to different genomic contexts. Methods: A cohort of 361 DLBCL patients (94 MYD88 mutant and 267 MYD88 wild-type) was selected among the prospective, multicenter and randomized LNH-03B and LNH09-7B (NCT01195714) LYSA trials, as well as among patients sequenced at our institution as part of routine procedure. Cell of origin (COO) classification was obtained with HGU133+2.0 Affymetrix GeneChip arrays for 214 patients, with RT-MLPA for 77 patients1 and with Hans immunohistochemistry (IHC) method for 49 patients. All cases were submitted to next generation sequencing (NGS) focusing on 34 genes (Lymphopanel2) in order to analyze associated mutations and copy number variations (CNVs), as well as IHC, FISH, and clinical and prognostic analyses. Results: Importantly, we highlighted different genomic profiles for MYD88 L265P and MYD88 non-L265P mutant DLBCL, shedding light on their divergent backgrounds. Clustering analysis segregated subgroups according to associated genetic alterations among patients with either MYD88 L265P or non-L265P mutations. As such, clustering separated MYD88 L265P mutated DLBCL with associated PIM1 (52%), CD79B (52%), KMT2D (42%), and PRDM1 (32%) mutations, as well as MYD88 L265P mutated DLBCL with CDKN2A/B (67%/50%), PRDM1 (57%) and TNFAIP3 (52%) CNVs. We showed that associated CD79B and MYD88 L265P mutations act synergistically to increase NFkB pathway activation, although the majority of ABC MYD88 L265P mutant cases harbor downstream NFkB alterations, which can potentially predict BTK inhibitor resistance. Of note, although the MYD88 L265P variant was not an independent prognostic factor in ABC DLBCL, associated CD79B mutations significantly improved the survival of MYD88 L265P mutant ABC DLBCL in our cohort both in OS (p=0.02) and PFS (p=0.01), whereas the association of CARD11 or TNFAIP3 alterations did not impact survival. Interestingly, MYD88 mutant DLBCL cases were significantly more likely to experience central nervous system (CNS) relapse than MYD88 WT cases (p=0.02), as were MYD88 L265P mutant cases specifically (p=0.03). This result still tended toward statistical significance when considering only ABC patients (7 of 11 ABC CNS-relapsing cases were MYD88 mutant, p=0.1) but would have to be confirmed in a larger cohort. Conclusions: This study highlights the relative heterogeneity of MYD88 mutant DLBCBL, adding to the field's knowledge of the distinct genetic backgrounds of these subgroups. Our data highlights the theranostic and prognostic relevance of examining MYD88 and associated genomic alterations, emphasizing the usefulness of genomic profiling to best stratify patients for targeted therapy. 1. Mareschal S, Ruminy P, Bagacean C, et al. Accurate Classification of Germinal Center B-Cell-Like/Activated B-Cell-Like Diffuse Large B-Cell Lymphoma Using a Simple and Rapid Reverse Transcriptase-Multiplex Ligation-Dependent Probe Amplification Assay: A CALYM Study. The Journal of molecular diagnostics : JMD. 2015;17(3):273-283. 2. Dubois S, Viailly P-J, Mareschal S, et al. Next Generation Sequencing in Diffuse Large B Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study. Clinical cancer research : an official journal of the American Association for Cancer Research. 2016;22(12):2919-2928. Disclosures Salles: Novartis: Consultancy, Honoraria; Mundipharma: Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding.
Published: 2017
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32. Photo-electrocatalytic performance of poly(3,4-ethylenedioxythiophene)/TiO2 nano-tree films deposited by oCVD/CVD for H2 production

Author: Amr A. Nada, Maged F. Bekheet, Diane Samelor, Hugues Vergnes, Christina Villeneuve-Faure, Jim Cartier, Christophe Charmette, Sophie Tingry, Brigitte Caussat, Constantin Vahlas, stéphanie Roualdes, Institut Carnot Chimie Balard Cirimat, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Institut Européen des membranes (IEM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Laboratoire de Génie Chimique (LGC), Université de Toulouse (UT), Institut Pierre-Simon-Laplace (IPSL (FR_636)), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Technische Universität Berlin, Faculty III Process Sciences, Institute of Material Science and Technology, Chair of Advanced Ceramic Materials, (Berlin, Germany), Diélectriques Solides et Fiabilité (LAPLACE-DSF), LAboratoire PLasma et Conversion d'Energie (LAPLACE), and Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: TiO2, [CHIM]Chemical Sciences, Water splitting, CVD, [2 1 1] anatase facet, PEDOT, Photo-anode
Abstract: The hydrogen production from photo-electrocatalytic water splitting attracts extensive attention as a direct way to convert solar energy into chemical fuels. In this work, innovative photo-anodes composed of TiO2 which has a preferable growth orientation [2 1 1] conjugated with PEDOT as bi-layers are prepared by a dry process strategy, combining oxidative and metalorganic chemical vapor deposition (CVD). Pure anatase, dendritic TiO2 films of variable thickness are obtained at 500 °C by varying the deposition time. Increase of films thickness from 474 to 2133 nm results in morphologies that evolve from dense and angular structures to isolated and nanostructured tree-like columns with a concomitant decrease of the charge transfer resistance due to the enhancement of active facets of anatase structure. The PEDOT/TiO2 bi-layer with an overall thickness of 1350 nm and a 50 nm thick upper-PEDOT layer exhibits the highest photocurrent response (0.26 mA cm−2 at 1.8 V/RHE), a fast photocurrent response under illumination, and the best hydrogen yield up to 4.1 µmol cm-2h−1 with electronic conductivity being three order of magnitude higher than pristine TiO2
Published: 2023
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33. BCL2 mutations do not confer adverse prognosis in follicular lymphoma patients treated with rituximab

Author: Catherine Chassagne-Clément, Elizabeth Punnoose, Luc Xerri, Sarah Huet, Wayne J. Fairbrother, Kiran Mukhyala, Laurie Tonon, Edith Szafer-Glusman, Alain Viari, Pierre Sujobert, Gilles Salles, Pierre Feugier, Christopher R. Bolen, Bruno Tesson, Fabrice Jardin, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Genentech, Inc., Genentech, Inc. [San Francisco], Institut Carnot CALYM [Pierre-Benite], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Aix Marseille Université (AMU), Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Institut Carnot Lymphome (CALYM), Fondation Synergie Lyon Cancer [Lyon], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)
Subjects: Male, 0301 basic medicine, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Follicular lymphoma, Antineoplastic Agents, Context (language use), medicine.disease_cause, Translocation, Genetic, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Activation-induced (cytidine) deaminase, Humans, Prospective cohort study, Lymphoma, Follicular, Mutation, biology, business.industry, Hematology, Cytidine deaminase, Prognosis, medicine.disease, Lymphoma, Treatment Outcome, 030104 developmental biology, Proto-Oncogene Proteins c-bcl-2, 030220 oncology & carcinogenesis, Immunology, biology.protein, Female, Rituximab, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, medicine.drug
Abstract: International audience; BCL2 mutations have been suggested to confer an adverse prognosis to follicular lymphoma (FL) patients, but their prognostic value has not been assessed in patients treated with a rituximab-containing regimen. Here we evaluated the prognostic value of BCL2 mutations in a large prospective cohort of 252 patients with FL treated with immunochemotherapy in the PRIMA randomized trial. Using a DNA-targeted sequencing approach, we detected amino acid altering mutations in 135 patients (54%) and showed that these mutations were probably mediated by the over-activation of AICDA (activation-induced cytidine deaminase) in the context of the t(14;18) translocation. The BCL2 variants identified in PRIMA patients affected the BH1, BH2, and BH3 functional motifs at a lower frequency than the N-terminus and flexible loop domain, with mostly conservative aminoacid changes. With a median follow-up of 6.7 years, we did not observe any impact of BCL2 mutations either on overall survival or progression-free survival.
Published: 2017
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34. Composition, texture and methane potential of cellulosic residues from Lewis acids organosolv pulping of wheat straw

Author: Abdellatif Barakat, Françoise Quignard, Claire Dumas, Francesco Di Renzo, Sandra Constant, Mike Robitzer, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Carnot Chimie Balard Institut Carnot Chimie Balard, GDR INRA-CNRS Biomatpro, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), ANR: Institut Carnot Chimie Balard,Institut Carnot Chimie Balard, Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, acide de lewis, Organosolv, Surface area, 010501 environmental sciences, biomasse lignocellulosique, 01 natural sciences, Lignin, chemistry.chemical_compound, Spectroscopy, Fourier Transform Infrared, Organic chemistry, valorisation des lignocelluloses, Lewis acids and bases, Waste Management and Disposal, ComputingMilieux_MISCELLANEOUS, Triticum, Lewis Acids, paille de blé, valorisation de la biomasse, Chemistry, Pulp (paper), Temperature, food and beverages, General Medicine, [CHIM.MATE]Chemical Sciences/Material chemistry, Straw, Biodegradability, Biodegradation, Environmental, Process Engineering, Cellulosic ethanol, Epidermal structure, prétraitement, fibre cellulosique, Crystallization, Methane, Porosity, Biotechnology, Biomass valorisation, Environmental Engineering, déchet cellulosique, Bioengineering, engineering.material, stomatognathic system, Polysaccharides, 010608 biotechnology, Hemicellulose, Cellulose, Homogeneous catalysis, Ethanosolv, Génie des procédés, 0105 earth and related environmental sciences, Waste Products, Renewable Energy, Sustainability and the Environment, biodégradabilité, stomatognathic diseases, Chemical engineering, engineering, Adsorption
Abstract: International audience; Cellulosic pulps have been successfully isolated from wheat straw through a Lewis acids organosolv treatment. The use of Lewis acids with different hardness produced pulps with different delignification degrees. The cellulosic residue was characterised by chemical composition, X-ray diffraction, FT-IR spectroscopy, N2 physisorption, scanning electron microscopy and potential for anaerobic digestibility. Surface area and pore volume increased with the hardness of the Lewis acid, in correspondence with the decrease of the amount of lignin and hemicellulose in the pulp. The non linearity of the correlation between porosity and composition suggests that an agglomeration of cellulose fibrils occurs in the early stages of pulping. All organosolv pulps presented a significantly higher methane potential than the parent straw. A methane evolution of 295 Ncm3/g OM was reached by a moderate improvement of the accessibility of the native straw.
Published: 2016
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35. The Composition of the Culture Medium Influences the β-1,3-Glucan Metabolism of Aspergillus fumigatus and the Antifungal Activity of Inhibitors of β-1,3-Glucan Synthesis

Author: Anne Beauvais, Jean-Paul Latgé, Cécile Clavaud, Lise Barbin, Hélène Munier-Lehmann, Aspergillus, Institut Pasteur [Paris] (IP), Centre hospitalier universitaire de Nantes (CHU Nantes), Chimie et Biocatalyse - Chemistry and Biocatalysis (group), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was partly supported by an Institut Carnot Pasteur Maladies Infectieuses grant (FUNGI), an education grant from Merck (1007005/00), and the Era-Pathogenomic grant Antifun, Institut Pasteur [Paris], Chimie et Biocatalyse, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), and This work was partly supported by an Institut Carnot Pasteur Maladies Infectieuses grant (FUNGI), an education grant from Merck (1007005/00), and the Era-Pathogenomic grant Antifun.
Subjects: Antifungal Agents, beta-Glucans, Miconazole, [SDV]Life Sciences [q-bio], MESH: Glycosides, Aspergillus fumigatus, Terpene, Echinocandins, MESH: Lipopeptides, Caspofungin, Pharmacology (medical), Glycosides, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, chemistry.chemical_classification, Analytical Procedures, MESH: Microbial Sensitivity Tests, 0303 health sciences, MESH: beta-Glucans, biology, Chitin synthase, 3. Good health, Infectious Diseases, Biochemistry, MESH: Aspergillus fumigatus, medicine.drug, Microbial Sensitivity Tests, macromolecular substances, Microbiology, Lipopeptides, 03 medical and health sciences, medicine, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, Pharmacology, MESH: Miconazole, 030306 microbiology, MESH: Echinocandins, MESH: Triterpenes, Glycoside, Metabolism, MESH: Antifungal Agents, biology.organism_classification, Triterpenes, In vitro, Culture Media, carbohydrates (lipids), chemistry, MESH: Culture Media, biology.protein
Abstract: In vitro testing of Aspergillus fumigatus susceptibility to echinocandins has always been a challenge. Using a simple and quick colorimetric method to analyze the activity of inhibitors of β-1,3-glucan synthesis, we found that the composition of the culture medium significantly influences glucan synthesis and consequently the antifungal properties of inhibitors of β-1,3-glucan synthesis when they are tested alone or in combination with chitin synthase inhibitors.
Published: 2012
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36. Thermal Management Design of Transformers for Dual Active Bridge Power Converters

Author: Gerard Delette, Ulrich Soupremanien, Serge Loudot, Département des Technologies des NanoMatériaux (DTNM), Laboratoire d'Innovation pour les Technologies des Energies Nouvelles et les nanomatériaux (LITEN), Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Renault Research Department, RENAULT, and the 'Institut CARNOT Energies du Futur'
Subjects: [CHIM.MATE]Chemical Sciences/Material chemistry, Electrical and Electronic Engineering
Abstract: International audience; A methodology for the design of compact transformers operating at high frequency is presented in this paper. A particular emphasis is paid to the thermal management of the magnetic core and of the winding components. For a 7kW Dual Active Bridge DC/DC converter, the objective is to reduce the core volume (< 60 cm3), improve the power efficiency (> 99 %) and integrate the serial inductance (8.7 µH) as being the leakage inductance of the transformer. A parametric study shows that the heating in the copper winding is very sensitive to the anisotropic thermal conduction behaviour of the wire. Due to this characteristic, a pot-core configuration is prone to a higher warming compared to the E-E core geometry, as the efficiency of the winding cooling is lower. In order to take part of the self-shielding ability of pot-cores, we studied new configurations in which internal thermal drains are inserted into voids specially designed to shorten the distance between the external cooled walls and the hottest points of the winding. The heating of internal components of the transformer and resulting thermal stress peak is reduced by 40 % paving the way for robust transformers with a power density that could theoretically reach up to 200 kW/dm3.
Published: 2022
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37. Qualitative monitoring of SARS-CoV-2 mRNA vaccination in humans using droplet microfluidics

Author: Broketa, Matteo, Sokal, Aurélien, Mor, Michael, Canales-Herrerias, Pablo, Perima, Angga, Meola, Annalisa, Fernández, Ignacio, Iannascoli, Bruno, Chenon, Guilhem, Vandenberghe, Alexis, Languille, Laetitia, Michel, Marc, Godeau, Bertrand, Gallien, Sebastien, Melica, Giovanna, Backovic, Marija, Rey, Felix, Baudry, Jean, Freund, Natalia, Mahevas, Matthieu, Bruhns, Pierre, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Diaccurate SAS, Physiologie, physiopathologie et thérapeutique (ED 394), Sorbonne Université (SU), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Tel Aviv University (TAU), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire Colloïdes et Matériaux Divisés (LCMD), Chimie-Biologie-Innovation (UMR 8231) (CBI), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), M.B. is the recipient of a CIFRE PhD fellowship. P.C-H. was supported by a fellowship from the French Fondation pour la Recherche Médicale (FRM). A.S. was supported by a Poste d’Accueil from INSERM, I.F. by a fellowship from the French Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS). P.B. acknowledges funding from the Agence Nationale de la Recherche (ANR) ANR-18-CE15-0001 project Autoimmuni-B and ANR-14-CE16-0011 project DROPmAbs, from the Institut Carnot Pasteur Microbes et Santé, from the CAPNET (Comité ad-hoc de pilotage national des essais thérapeutiques et autres recherches, French government) MEMO-VOC, from the Institut Pasteur and from the Institut National de la Santé et de la Recherche Médicale (INSERM). M.Ma. acknowledges funding from the Agence Nationale de la Recherche and the Fondation pour la Recherche Médicale (ANR, MEMO-COV-2 -FRM). Assistance Publique – Hôpitaux de Paris (AP-HP, Département de la Recherche Clinique et du Développement) was the promotor and the sponsor of MEMO-COV-2. J.B. acknowledges funding from the French government through BPIFrance under the frame Programme d’Investissements d’Avenir (CELLIGO Project), the Institut Pierre-Gilles de Gennes through the laboratoire d’excellence, Investissements d’avenir programs ANR-10-IDEX-0001-02 PSL, ANR-10- EQPX-34 and ANR-10-LABX-3. N.T.F. acknowledges funding from the Israeli Science Foundation grants #1422/18 and #3711/20 and Marguerite Stolz Research Fellowship. Work in the Unit of Structural Virology was funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur., ANR-18-CE15-0001,Autoimmuni-B,Etude de la rupture de tolérance dans une maladie humaine autoimmune médiée par les lymphocytes B(2018), ANR-14-CE16-0011,DROP-mAbs,Analyse en profondeur de répertoires d'anticorps par microfluidique en gouttelettes couplé à du séquençage haut-débit pour le diagnostic et la découverte d'anticorps thérapeutiques(2014), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-10-EQPX-0034,IPGG,Institut Pierre Gilles de Gennes pour la microfluidique(2010), and ANR-10-LABX-0003,BCDiv,Biological and Cultural Diversities : Origins, Evolution, Interactions, Future(2010)
Subjects: [SDV]Life Sciences [q-bio], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Abstract: International audience; SARS-CoV-2 mRNA vaccination generates protective B cell responses targeting the SARS-CoV-2 spike glycoprotein. Whereas anti-spike memory B cell responses are long-lasting, the anti-spike humoral antibody response progressively wanes, making booster vaccinations necessary for maintaining protective immunity. Here we investigated qualitatively the plasmablast responses by measuring from single cells within hours of sampling the affinity of their secreted antibody for the SARS-CoV-2 spike receptor binding domain in cohorts of BNT162b2-vaccinated naive and COVID-19-recovered individuals. Using a unique droplet microfluidic and imaging approach, we analyzed >4,000 single IgG-secreting cells revealing high inter-individual variability in affinity for RBD with variations over 4 logs. High-affinity plasmablasts were induced by BNT162b2 vaccination against Hu-1 and Omicron RBD but disappeared quickly thereafter, whereas low-affinity plasmablasts represented >65% of the plasmablast response at all timepoints. Our droplet-based method thus proves efficient at fast and qualitative immune monitoring and should be helpful for optimization of vaccination protocols.
Published: 2023
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38. Investigation of Chemical and Thermal Stability of Li7−xLa3Zr2−xTaxO12 Garnet Type Solid-State Electrolyte to Assemble Self-Standing Li-based All Solid-State Battery

Author: Charrad, Ghassen, Pradeilles, Sarah, Berthelot, Romain, Taberna, P.-L., Simon, Patrice, Rozier, Patrick, Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), Réseau sur le stockage électrochimique de l'énergie (RS2E), Aix Marseille Université (AMU)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Collège de France (CdF (institution))-Université de Picardie Jules Verne (UPJV)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Université Grenoble Alpes (UGA)-Nantes Université (Nantes Univ)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), and ANR-16-CARN-0008,UT ,Institut Carnot
Subjects: Garnet structure type, Layered oxides, Solid-State electrolytes, Spark plasma sintering, All solid-state batteries, [CHIM]Chemical Sciences
Abstract: All solid-state batteries (ASSB) are the next generation of safe and high-energy-density energy storage technology. Their development is currently impeded by the stability issues of solid-state electrolyte (SSE) limiting the creation of interfaces of quality high enough to ensure efficient transfer of charges. The garnet Li7−xLa3Zr2−xTaxO12 (LLZO:Ta) is one of the most appealing oxide-based SSE but its high sensitivity to moist air engenders difficulties in designing process to densify and assemble components of the ASSB. Based on a careful investigation of LLZO:Ta thermal and chemical stability, a heat treatment is designed and shown to fully reverse the protonation process. The investigation of spark plasma sintering protocols confirms that pretreated LLZO:Ta can be densified at a temperature as low as 850 °C or with a short duration (few seconds) at 900 °C. The characterization of obtained ceramics shows conductivities close to the bulk properties and confirms the absence of influence of grain boundaries. The study of composite electrodes shows that LLZO:Ta is suitable to act both as SSE separator and ionic percolator in positive electrode, the selection of active material remains the main issue to target self-standing Li-based ASSB.
Published: 2023
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39. Complete Genome Sequences of Monkeypox Virus from a French Clinical Sample and the Corresponding Isolated Strain, Obtained Using Nanopore Sequencing

Author: Charlotte Balière, Véronique Hourdel, Aurelia Kwasiborski, Quentin Grassin, Maxence Feher, Damien Hoinard, Jessica Vanhomwegen, Fabien Taieb, Paul-Henri Consigny, Jean-Claude Manuguerra, India Leclercq, Christophe Batéjat, Valérie Caro, Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre Médical de l'Institut Pasteur (CMIP), and This project received funding from the French Institut Carnot 'Microbes-Santé' in collaboration with the 'France Futur Elevage' Carnot of INRAE Institute, in the framework of the FIELD project.
Subjects: Immunology and Microbiology (miscellaneous), [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genetics, Molecular Biology
Abstract: International audience; We report the whole-genome sequences of a monkeypox virus from the skin lesion of a French patient and the corresponding isolated viral strain. Both viral genomic sequences were successfully obtained by applying shotgun metagenomics using the Oxford Nanopore Technologies sequencing approach.
Published: 2023
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40. Modeling and LES of High-Pressure Liquid Injection Under Evaporating and Non-Evaporating Conditions by a Real Fluid Model and Surface Density Approach

Author: Gaballa, Hesham, Habchi, Chaouki, de Hemptinne, Jean-Charles, IFP Energies nouvelles (IFPEN), Institut Carnot IFPEN Transports Energie, IFP Energies nouvelles (IFPEN)-IFP Energies nouvelles (IFPEN), and European Project: 861002
Subjects: Fluid Flow and Transfer Processes, MESH: Real-fluid model, Thermodynamic tabulation, Vapor–liquid equilibriumLarge eddy simulation, Atomization, Engine Combustion, Network (ECN) Spray A, Engine Combustion Network (ECN) Spray A, [SPI]Engineering Sciences [physics], Vapor-liquid equilibrium, Mechanical Engineering, Large eddy simulation, General Physics and Astronomy, Real-fluid model, [CHIM]Chemical Sciences, [MATH]Mathematics [math]
Abstract: International audience; Numerical modeling of high-pressure liquid fuel injection remains a challenge in various applications. Indeed, experimental observations have shown that injected liquid fuel jet undergoes a continuous change of state from classical two-phase atomization and spray droplets evaporation to a dense-fluid mixing phenomenon depending on the ambient pressure, temperature, and fuel properties. Accordingly, a predictive and efficient computational fluid dynamics (CFD) model that can represent the possible coexistence of subcritical and supercritical regimes during the fuel injection event is required. The widely used Lagrangian Discrete Droplet Method (DDM) requires parameter tuning of model constants and cannot model the dense near-nozzle region. Meanwhile, the high computational cost of Interface Capturing Methods (ICM) has prohibited their application to industrial cases. Thus, another alternative is an Eulerian Diffuse Interface Model (DIM), where the unresolved interface features are modeled instead of being tracked. Accordingly, the current work proposes a fully compressible multi-component two-phase real-fluid model (RFM) with a diffused interface and closed by a thermodynamic equilibrium tabulation method based on a real-fluid equation of state. The RFM model is complemented with a postulated surface density equation for fuel atomization modeling within the Large Eddy Simulation (LES) framework. The Engine Combustion Network (ECN) Spray A injector non-evaporating and nominal evaporating conditions are used as a reference for the proposed model validation. Simulations are performed using the proposed RFM model that has been implemented in the CONVERGE CFD solver. Under the non-evaporating condition, the RFM model can capture well the fuel mass distribution in the near-nozzle field, but also the interfacial surface area. Besides, the predicted drop size from simulations falls within the experimental data range. On the other hand, under the evaporating condition, spray liquid and vapor penetrations and fuel mixture fraction distribution are also accurately predicted. The vaporization effect on the surface area density is revealed to enhance surface generation in the dense spray region while reducing the surface density in the dilute spray region. The mean droplet size is also relatively reduced under the evaporating condition in the diluted spray region. Overall, the accuracy and computationally efficiency of the proposed RFM model coupled with the surface density equation for high-pressure fuel injection modeling are confirmed, allowing its use for high pressure industrial configurations in future studies.
Published: 2023
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41. Human monocyte recognition of adenosine-based cyclic dinucleotides unveils the A2a Gαs protein-coupled receptor tonic inhibition of mitochondrially induced cell death

Author: Emmanuel Ravet, Gérard Tiraby, Eric Perouzel, Frédéric Pont, Marc Poirot, Laetitia Ligat, Jean-Jacques Fournié, Mary Poupot, Frédéric Lopez, Els Verhoeyen, Marie Tosolini, Delphine Betous, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d’Excellence ‘TOUCAN’ [Toulouse], Institut Carnot Lymphome (CALYM), InvivoGen Europe, Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Davoine, Laure-Hélène, Endocrinologie et communication cellulaire, Institut Louis Bugnard-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (Equipe EVIR), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Carnot CALYM [Pierre-Benite], Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Programmed cell death, Adenosine, Receptor, Adenosine A2A, [SDV.IMM] Life Sciences [q-bio]/Immunology, Biology, Inbred C57BL, Small Interfering, Monocytes, 03 medical and health sciences, Adenosine A2A, Mice, 0302 clinical medicine, medicine, Cyclic AMP, Animals, Humans, RNA, Small Interfering, Phosphorylation, Protein kinase A, Receptor, Molecular Biology, 030304 developmental biology, G protein-coupled receptor, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Cell Death, Monocyte, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Articles, Cell Biology, Adenosine receptor, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Cell biology, Mitochondria, Mice, Inbred C57BL, medicine.anatomical_structure, Mitochondrial permeability transition pore, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030217 neurology & neurosurgery, medicine.drug, Signal Transduction
Abstract: International audience; Cyclic dinucleotides are important messengers for bacteria and protozoa and are well-characterized immunity alarmins for infected mammalian cells through intracellular binding to STING receptors. We sought to investigate their unknown extracellular effects by adding cyclic dinucleotides to the culture medium of freshly isolated human blood cells in vitro. Here we report that adenosine-containing cyclic dinucleotides induce the selective apoptosis of monocytes through a novel apoptotic pathway. We demonstrate that these compounds are inverse agonist ligands of A2a, a Gαs-coupled adenosine receptor selectively expressed by monocytes. Inhibition of monocyte A2a by these ligands induces apoptosis through a mechanism independent of that of the STING receptors. The blockade of basal (adenosine-free) signaling from A2a inhibits protein kinase A (PKA) activity, thereby recruiting cytosolic p53, which opens the mitochondrial permeability transition pore and impairs mitochondrial respiration, resulting in apoptosis. A2a antagonists and inverse agonist ligands induce apoptosis of human monocytes, while A2a agonists are antiapoptotic. In vivo, we used a mock developing human hematopoietic system through NSG mice transplanted with human CD34(+) cells. Treatment with cyclic di-AMP selectively depleted A2a-expressing monocytes and their precursors via apoptosis. Thus, monocyte recognition of cyclic dinucleotides unravels a novel proapoptotic pathway: the A2a Gαs protein-coupled receptor (GPCR)-driven tonic inhibitory signaling of mitochondrion-induced cell death.
Published: 2015
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42. Temperature-sensitive mutants in the influenza A virus RNA polymerase: alterations in the PA linker reduce nuclear targeting of the PB1-PA dimer and result in viral attenuation

Author: Bernard Delmas, Sandie Munier, Ronan Le Goffic, Alexandre Ghounaris, Alix Sausset, Bruno Da Costa, Nadia Naffakh, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7), Génétique moléculaire des virus à ARN, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), B.D. acknowledges the support of the ANR Blanc program (RNAP-IAV project), the support of Institut Carnot Santé Animale (Flu-MLI project), and the support of Paris-Saclay University (Programme prévalorisation 2014). N.N. acknowledges the support of the Institut Carnot Pasteur Maladies Infectieuses and of the European Commission-funded FP7 project FLUPHARM, grant agreement 259751., ANR-14-CE09-0017,RNAP-IAV,Interactions protéine-protéine et protéine-ARN au sein du complexe réplicatif du virus de la grippe de type A(2014), European Project: 259751,EC:FP7:HEALTH,FP7-INFLUENZA-2010,FLU-PHARM(2010), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: viruses, [SDV]Life Sciences [q-bio], Immunology, Mutant, Active Transport, Cell Nucleus, RNA-dependent RNA polymerase, Virus Replication, Microbiology, Protein Structure, Secondary, Viral Proteins, chemistry.chemical_compound, Influenza A Virus, H1N1 Subtype, Transcription (biology), Protein-fragment complementation assay, Virology, RNA polymerase, Animals, Humans, Protein Interaction Domains and Motifs, Polymerase, Mice, Inbred BALB C, biology, Circular Dichroism, Structure and Assembly, Genetic Complementation Test, Temperature, RNA, biochemical phenomena, metabolism, and nutrition, RNA-Dependent RNA Polymerase, Molecular biology, 3. Good health, Mice, Inbred C57BL, Viral replication, chemistry, Insect Science, Mutation, biology.protein, Female, Mutant Proteins, Protein Binding
Abstract: The influenza virus RNA-dependent RNA polymerase catalyzes genome replication and transcription within the cell nucleus. Efficient nuclear import and assembly of the polymerase subunits PB1, PB2, and PA are critical steps in the virus life cycle. We investigated the structure and function of the PA linker (residues 197 to 256), located between its N-terminal endonuclease domain and its C-terminal structured domain that binds PB1, the polymerase core. Circular dichroism experiments revealed that the PA linker by itself is structurally disordered. A large series of PA linker mutants exhibited a temperature-sensitive ( ts ) phenotype (reduced viral growth at 39.5°C versus 37°C/33°C), suggesting an alteration of folding kinetic parameters. The ts phenotype was associated with a reduced efficiency of replication/transcription of a pseudoviral reporter RNA in a minireplicon assay. Using a fluorescent-tagged PB1, we observed that ts and lethal PA mutants did not efficiently recruit PB1 to reach the nucleus at 39.5°C. A protein complementation assay using PA mutants, PB1, and β-importin IPO5 tagged with fragments of the Gaussia princeps luciferase showed that increasing the temperature negatively modulated the PA-PB1 and the PA-PB1-IPO5 interactions or complex stability. The selection of revertant viruses allowed the identification of different types of compensatory mutations located in one or the other of the three polymerase subunits. Two ts mutants were shown to be attenuated and able to induce antibodies in mice. Taken together, our results identify a PA domain critical for PB1-PA nuclear import and that is a “hot spot” to engineer ts mutants that could be used to design novel attenuated vaccines. IMPORTANCE By targeting a discrete domain of the PA polymerase subunit of influenza virus, we were able to identify a series of 9 amino acid positions that are appropriate to engineer temperature-sensitive ( ts ) mutants. This is the first time that a large number of ts mutations were engineered in such a short domain, demonstrating that rational design of ts mutants can be achieved. We were able to associate this phenotype with a defect of transport of the PA-PB1 complex into the nucleus. Reversion substitutions restored the ability of the complex to move to the nucleus. Two of these ts mutants were shown to be attenuated and able to produce antibodies in mice. These results are of high interest for the design of novel attenuated vaccines and to develop new antiviral drugs.
Published: 2015
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43. EZH2 alterations in follicular lymphoma: biological and clinical correlations

Author: Julien Lazarovici, Gilles Salles, Marjorie Carrère, Lenaïg Mescam-Mancini, Alain Viari, Emilie Sohier, Olivier Casasnovas, Corinne Haioun, Sandrine Boyault, Sebastien Taix, Luc Xerri, Laurie Tonon, Bettina Fabiani, Sylvain Mareschal, Sandrine Hayette, Bruno Tesson, Sarah Huet, Fabrice Jardin, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Carnot Lymphome (CALYM), Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université Paris-Saclay, Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut Carnot CALYM [Pierre-Benite], and Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)
Subjects: Adult, Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Follicular lymphoma, macromolecular substances, Biology, Methylation, Polymorphism, Single Nucleotide, Disease-Free Survival, 03 medical and health sciences, Histone H3, symbols.namesake, Cell Line, Tumor, medicine, Humans, Enhancer of Zeste Homolog 2 Protein, Lymphoma, Follicular, Aged, Sanger sequencing, Regulation of gene expression, Sequence Analysis, RNA, EZH2, Histone-Lysine N-Methyltransferase, Hematology, Middle Aged, medicine.disease, 3. Good health, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, Histone methyltransferase, Mutation, Histone Methyltransferases, Mutation testing, symbols, Cancer research, Original Article, Female
Abstract: The histone methyltransferase EZH2 has an essential role in the development of follicular lymphoma (FL). Recurrent gain-of-function mutations in EZH2 have been described in 25% of FL patients and induce aberrant methylation of histone H3 lysine 27 (H3K27). We evaluated the role of EZH2 genomic gains in FL biology. Using RNA sequencing, Sanger sequencing and SNP-arrays, the mutation status, copy-number and gene-expression profiles of EZH2 were assessed in a cohort of 159 FL patients from the PRIMA trial. Immunohistochemical (IHC) EZH2 expression (n=55) and H3K27 methylation (n=63) profiles were also evaluated. In total, 37% of patients (59/159) harbored an alteration in the EZH2 gene (mutation n=46, gain n=23). Both types of alterations were associated with highly similar transcriptional changes, with increased proliferation programs. An H3K27me3/me2 IHC score fully distinguished mutated from wild-type samples, showing its applicability as surrogate for EZH2 mutation analysis. However, this score did not predict the presence of gains at the EZH2 locus. The presence of an EZH2 genetic alteration was an independent factor associated with a longer progression-free survival (hazard ratio 0.58, 95% confidence interval 0.36–0.93, P=0.025). We propose that the copy-number status of EZH2 should also be considered when evaluating patient stratification and selecting patients for EZH2 inhibitor-targeted therapies.
Published: 2017
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44. Study of the host specificity of PB1-F2-associated virulence

Author: Joelle Mettier, Daniel Marc, Ronan Le Goffic, Laura Sedano, Bruno Da Costa, Christophe Chevalier, Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Carnot Santé Animale (France) (Influenza-2011 and FlumLi), Ministère de l'Agriculture et de l'Alimentation (France), Délégation Générale de l'Alimentation (France) (FRIA2019, PREDYT), ANR-17-CE35-0007,REACTIV,Réassortiment, Emergence et Facteur de Virulence des Virus Influenza A(2017), and Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Microbiology (medical), animal structures, Virulence Factors, viruses, mouse model, Immunology, Reassortment, zoonotic viruses, Virulence, Infectious and parasitic diseases, RC109-216, Biology, Microbiology, Host Specificity, Virus, Virulence factor, influenza virus, Mice, Viral Proteins, 03 medical and health sciences, pb1-f2, Orthomyxoviridae Infections, species barrier, Animals, h7n1, h3n2, Tropism, 030304 developmental biology, 0303 health sciences, 030306 microbiology, Host (biology), Influenza A Virus, H3N2 Subtype, Embryonated, virus diseases, biochemical phenomena, metabolism, and nutrition, Virology, In vitro, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Influenza A Virus, H7N1 Subtype, Parasitology, reassortment, intravital imaging, chicken infection, Chickens, Research Article, Research Paper
Abstract: International audience; Influenza A viruses cause important diseases in both human and animal. The PB1-F2 protein is a virulence factor expressed by some influenza viruses. Its deleterious action for the infected host is mostly described in mammals, while the available information is scarce in avian hosts. In this work, we compared the effects of PB1-F2 in avian and mammalian hosts by taking advantage of the zoonotic capabilities of an avian H7N1 virus. In vitro, the H7N1 virus did not behave differently when PB1-F2 was deficient while a H3N2 virus devoid of PB1-F2 was clearly less inflammatory. Likewise, when performing in vivo challenges of either chickens or embryonated eggs, with the wild-type or the PB1-F2 deficient virus, no difference could be observed in terms of mortality, host response or tropism. PB1-F2 therefore does not appear to play a major role as a virulence factor in the avian host. However, when infecting NF-κB-luciferase reporter mice with the H7N1 viruses, a massive PB1-F2-dependent inflammation was quantified, highlighting the host specificity of PB1-F2 virulence. Surprisingly, a chimeric 7:1 H3N2 virus harboring an H7N1-origin segment 2 (i.e. expressing the avian PB1-F2) induced a milder inflammatory response than its PB1-F2-deficient counterpart. This result shows that the pro-inflammatory activity of PB1-F2 is governed by complex mechanisms involving components from both the virus and its infected host. Thus, a mere exchange of segment 2 between strains is not sufficient to transmit the deleterious character of PB1-F2.
Published: 2021
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45. Proceeding of the 2022 IEEE 28th International Conference on Engineering, Technology and Innovation (ICE/ITMC) & 31st International Association For Management of Technology (IAMOT) Joint Conference

Author: Dupont, Laurent, Camargo, Mauricio, Morel, Laure, Equipe de Recherche sur les Processus Innovatifs (ERPI), Université de Lorraine (UL), Région Grand Est, Ecole Doctorale SIMPPE, Pole scientfique EMPP, Université de Lorraine, Groupe Actibac, ECTP, Ville de Nancy, HyValue Project, International Conference on Engineering, Technology and Innovation (ICE/ITMC), International Association For Management of Technology (IAMOT), Research Network on Innovation - RNI, Métropole Grand Nancy, Institut Carnot ICEEL, Octroi Nancy, Lorraine Fab Living Lab® (LF2L), IEEE TEMS, European Project: 869952,INEDIT, European Project: 870037,iProduce, European Project: 870148,DIY4U, European Project: 869984,OPEN_NEXT, and European Project: 873010,DigiTeRRI
Subjects: [SPI]Engineering Sciences [physics], [SHS.GESTION]Humanities and Social Sciences/Business administration
Published: 2023
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46. Long-term intake of Lacticaseibacillus helveticus enhances bioavailability of omega-3 fatty acids in the mouse retina

Author: Bringer, Marie-Agnès, Lapaquette, Pierre, Terrat, Sébastien, Proukhnitzky, Lil, Martine, Lucy, Grégoire, Stéphane, Buteau, Bénédicte, Rieu, Aurélie, Bermúdez-Humarán, Luis, Gabrielle, Pierre Henry, Creuzot‐Garcher, Catherine, Berdeaux, Olivier, Acar, Niyazi, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Bibliothèques universitaires [Université de Bourgogne] (BU), Université de Bourgogne (UB), Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Agence Nationale de la Recherche, INRAE, French 'Investissements d’Avenir' program, project ISITE-BFC, Conseil Régional de Bourgogne, Franche-Comté [PARI grant], FEDER (European Regional Development Fund) and Institut Carnot Qualiment [grant INPROBIAUS]., ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011), ANR-15-IDEX-0003,BFC,ISITE ' BFC(2015), European Project: FEDER, Julien, Sabine, Laboratoires d'excellence - Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - - Lipstic2011 - ANR-11-LABX-0021 - LABX - VALID, ISITE ' BFC - - BFC2015 - ANR-15-IDEX-0003 - IDEX - VALID, and FEDER - FEDER - INCOMING
Subjects: Microbiota, Probiotic, Retina, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Plasma, Docosahexaenoic acid, Metabolism, Liver, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 22 Fatty acids, Lactic acid bacteria, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Phospholipids
Abstract: Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), are required for the structure and function of the retina. They could also help to prevent or delay the development of retinopathies. Given the accumulating evidence showing the role of gut microbiota in regulating retinal physiology and host lipid metabolism, we evaluated the potential of long-term dietary supplementation with the Gram-positive bacterium Lacticaseibacillus helveticus strain VEL12193 to modulate the retinal n-3 PUFA content. A set of complementary approaches was used to study the impact of such a supplementation on the gut microbiota and host lipid/fatty acid (FA) metabolism. L. helveticus-supplementation was associated with a decrease in retinal saturated FAs (SFAs) and monounsaturated FAs (MUFAs) as well as an increase in retinal n-3 and omega-6 (n-6) PUFAs. Interestingly, supplementation with L. helveticus enriched the retina in C22:5n-3 (docosapentaenoic acid, DPA), C22:6n-3 (DHA), C18:2n-6 (linoleic acid, LA) and C20:3n-6 (dihomo gamma-linolenic acid, DGLA). Long-term consumption of L. helveticus also modulated gut microbiota composition and some changes in OTUs abundance correlated with the retinal FA content. This study provides a proof of concept that targeting the gut microbiota could be an effective strategy to modulate the retinal FA content, including that of protective n-3 PUFAs, thus opening paths for the design of novel preventive and/or therapeutical strategies for retinopathies.
Published: 2023

47. De l’interaction pointe-matière à la nanocaractérisation électrique et mécanique par AFM

Author: Germanicus, Rosine Coq, Luders, U., Laboratoire de cristallographie et sciences des matériaux (CRISMAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), and Les entreprises caennaises Murata, NXP et Presto Engineering ainsi que l’Institut CARNOT « énergie et systèmes de propulsion » et la région Normandie ont soutenu ces travaux à travers le financement de projets de recherche.
Subjects: [PHYS]Physics [physics], AFM - Atomic force microscopy, semiconducteurs, SCM, SSRM, sMIM, PFT-QNM, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics
Abstract: International audience; Depuis plus de 30 ans, la Microscopie à Force Atomique (AFM) a démontré sa capacité à accéder aux propriétés locales de la matière. Très connue pour l’acquisition de la topographie, la technique s’est dotée au fil des années de nombreux modes permettant notamment de cartographier les propriétés mécaniques et électriques à l’échelle nanométrique.Les travaux de recherches présentés dans cet ouvrage traitent quatre modes : le mode mécanique (le Peak Force Tapping Quantitative Nanomechanical Mapping (PF-QNM™)), et trois modes électriques (le Scanning Capacitance Microscopy (SCM), le Scanning Spreading Resistance Microscopy (SSRM) et le scanning Microwave Impedance Microscopy (sMIM)), spécifiquement pour la microélectronique fortement intégrée.De l’interaction pointe-matière à la nanocaractérisation électrique et mécanique par AFM présente les résultats expérimentaux pour différents cas d’études relatifs au composant microélectronique : du boitier packaging aux profils de dopage du semiconducteur. Basée sur la physique du contact à l’échelle nanoscopique, l’analyse fine de chaque mode expose l’impact des paramètres de mesure et parvient à la mise en place de méthodologies expérimentales.
Published: 2023

48. Discovery of Bis-Imidazoline Derivatives as New CXCR4 Ligands

Author: Zhicheng Zhou, Isabelle Staropoli, Anne Brelot, Peggy Suzanne, Aurélien Lesnard, Fanny Fontaine, Serge Perato, Sylvain Rault, Olivier Helynck, Fernando Arenzana-Seisdedos, Jana Sopkova-de Oliveira Santos, Bernard Lagane, Hélène Munier-Lehmann, Philippe Colin, Pathogénie Virale - Viral Pathogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Chimie et Biocatalyse, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This research was funded by Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur, Agence Nationale de Recherche sur le SIDA et les hépatites Virales (ANRS- MIE) and Institut Carnot Pasteur MI, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (Grant ANR-10-LABEX-62-IBEID). Z.Z. and P.C. were supported by a research fellowship from ANRS-MIE., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: CXCR4, [SDV]Life Sciences [q-bio], Organic Chemistry, Pharmaceutical Science, therapeutic target, antagonist, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, CXCL12, HIV-1 infection, Analytical Chemistry, bis-imidazoline, Chemistry (miscellaneous), Drug Discovery, Molecular Medicine, Physical and Theoretical Chemistry
Abstract: International audience; The chemokine receptor CXCR4 and its ligand CXCL12 regulate leukocyte trafficking, homeostasis and functions and are potential therapeutic targets in many diseases such as HIV-1 infection and cancers. Here, we identified new CXCR4 ligands in the CERMN chemical library using a FRET-based high-throughput screening assay. These are bis-imidazoline compounds comprising two imidazole rings linked by an alkyl chain. The molecules displace CXCL12 binding with submicromolar potencies, similarly to AMD3100, the only marketed CXCR4 ligand. They also inhibit anti-CXCR4 mAb 12G5 binding, CXCL12-mediated chemotaxis and HIV-1 infection. Further studies with newly synthesized derivatives pointed out to a role of alkyl chain length on the bis-imidazoline properties, with molecules with an even number of carbons equal to 8, 10 or 12 being the most potent. Interestingly, these differ in the functions of CXCR4 that they influence. Site-directed mutagenesis and molecular docking predict that the alkyl chain folds in such a way that the two imidazole groups become lodged in the transmembrane binding cavity of CXCR4. Results also suggest that the alkyl chain length influences how the imidazole rings positions in the cavity. These results may provide a basis for the design of new CXCR4 antagonists targeting specific functions of the receptor.
Published: 2023
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49. Microbiota-induced active translocation of peptidoglycan across the intestinal barrier dictates its within-host dissemination

Author: Richard Wheeler, Paulo André Dias Bastos, Olivier Disson, Aline Rifflet, Ilana Gabanyi, Julia Spielbauer, Marion Bérard, Marc Lecuit, Ivo Gomperts Boneca, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Microenvironnement et Immunité - Microenvironment and Immunity, Animalerie Centrale (plateforme) - Central Animal Facility (platform) (C2RA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre National de Référence Listeria - National Reference Center Listeria (CNR), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This project has received funding from the Institut Carnot Pasteur Microbes & Santé, and the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no 665807. A.R. and I.G.B. laboratory were supported by Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID). I.G.B. laboratory was also supported by the Investissement d’Avenir program (RHU Torino Lumière ANR-16-RHUS-0008), by the French National Research Agency (ANR-16-CE15-0021) and by R&D grants from Danone and MEIJI. Additional funding was provided by DIM1Health., We thank the UTechS PBI, a member of the France–BioImaging infrastructure network supported by the French National Research Agency (ANR-10–INSB–04, Investments for the future) for microscope usage and assistance. We thank the members of the Centre for Gnotobiology Platform of the Institut Pasteur (especially Thierry Angélique, Eddie Maranghi, Martine Jacob, and Marisa Gabriela Lopez Dieguez), and of the Institut Pasteur Central Animal Facility for all their assistance with animal studies. P.A.D.B. was part of the Pasteur-Paris University International PhD Program., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), ANR-16-CE15-0021,PG-Brain,Modulation de l'activité du cerveau par le peptidoglycan bactérien(2016), and European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015)
Subjects: Multidisciplinary, gut microbiota, systemic trafficking, [SDV.BA]Life Sciences [q-bio]/Animal biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], peptidoglycan, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; Peptidoglycan, the major structural polymer forming the cell wall of bacteria, is an important mediator of physiological and behavioral effects in mammalian hosts. These effects are frequently linked to its translocation from the intestinal lumen to host tissues. However, the modality and regulation of this translocation across the gut barrier has not been precisely addressed. In this study, we characterized the absorption of peptidoglycan across the intestine and its systemic dissemination. We report that peptidoglycan has a distinct tropism for host organs when absorbed via the gut, most notably by favoring access to the brain. We demonstrate that intestinal translocation of peptidoglycan occurs through a microbiota-induced active process. This process is regulated by the parasympathetic pathway via the muscarinic acetylcholine receptors. Together, this study reveals fundamental parameters concerning the uptake of a major microbiota molecular signal from the steady-state gut.
Published: 2023
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50. Les enjeux du Génie des Procédés pour la réutilisation des eaux usées traitées au sein du réseau REUSE d'INRAE – de la nécessité d'une approche pluridisciplinaire et multi-échelles

Author: Nassim Ait-Mouheb, Sami Bouarfa, Anne-Laure Collard, Christelle Guigui, Jérôme Labille, Rémi Lombard-Latune, Jean-Denis Mathias, Bruno Molle, Pascal Molle, Jaime Nivala, Dominique Patureau, Alain Rapaport, Nicolas Roche, Mathieu Sperandio, Severine Tomas, Jérôme Harmand, Gestion de l'Eau, Acteurs, Usages (UMR G-EAU), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Bureau de Recherches Géologiques et Minières (BRGM) (BRGM)-Institut de Recherche pour le Développement (IRD)-AgroParisTech-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Réduire, valoriser, réutiliser les ressources des eaux résiduaires (UR REVERSAAL), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire d'ingénierie pour les systèmes complexes (UR LISC), Laboratoire de Biotechnologie de l'Environnement [Narbonne] (LBE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Mathématiques, Informatique et STatistique pour l'Environnement et l'Agronomie (MISTEA), Université Polytechnique Mohammed VI - Benguerir (UM6P), and Le projet NEREIDE bénéficie d'un financement de l'Institut Carnot Eau et Environnement. Les projets WoD et BIOROC bénéficient de financements de la Région Occitanie dans le cadre du défi clé WATER Occitanie, de la Fondation AGROPOLIS et d'INRAE
Subjects: réseau REUSE d'INRAE, [SDE]Environmental Sciences, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, General Medicine, Génie des Procédés, eaux usées traitées
Abstract: International audience; The reuse of wastewater aims to mobilize and treat, for certain uses and under certain conditions, water that has already been used. Rather than discharging wastewater into the natural environment, this practice aims to recover it by replacing the mobilization of water withdrawn from the environment [van Loosdrecht and Brdjanovic, 2014]. By moving from a linear logic of the mobilization and use of water to a circular approach, the objective pursued is to reduce the pressure, qualitative then quantitative, on the resources while limiting, as far as possible, the usage conflicts. It is in fact a question of passing from a simple competitive mode which strongly mobilizes resources, to a complex mode, known as “circular”, of putting in complementarity of uses. This approach initially mainly concerned agricultural uses insofar as agricultural needs represent the majority of the water mobilized, including developed countries [UN Water 2018]. Cities integrate specific issues that are characterized by significantly different options from those that can be found in rural areas. In the city, the recovery of wastewater has both material aspects (water, nutrients, critical metals, biopolymers, etc.) and energy aspects (recovery of heat from the networks, production of energy by biological means and /or thermal,…) which should be integrated on an appropriate scale according to the problems addressed (housing, building, district, city, territory or hydrological basin). To study the conditions under which REUSE can develop and be implemented in a safe and sustainable manner, research is needed [Ait-Mouheb et al., 2018]. If it represents an opportunity in certain territories where wastewater can be mobilized, it is also necessary to underline the limits of this practice in territories where the wastewater discharged into the environment is necessary to maintain the low water levels of rivers and rivers, or where soils may be affected, for example, by the salinity of these waters. In addition, studies of the social, economic and environmental dimensions differ significantly depending on the uses envisaged and the situations considered. To meet these challenges, the REUSE network of INRAE (cf. www6.inrae.fr) proposes to adopt a multidisciplinary and multi-scale approach by mobilizing not only the disciplines that can be considered as falling within the field of technologies and environmental engineering but also all of those relating to the human and social sciences, economics, legal, and participatory sciences.
Published: 2023
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