395 results on '"French Ministry of Higher Education"'
Search Results
2. A multi-scale analysis of bull sperm methylome revealed both species peculiarities and conserved tissue-specific
- Author
-
French National Research Agency, French Ministry of Higher Education, Perrier, Jean-Philippe, Sellem, Eli, Prézelin, Audrey, Gasselin, Maxime, Jouneau, Luc, Piumi, François, Adhami, Hala Al, Weber, Michaël, Fritz, Sébastien, Boichard, Didier, Le Danvic, Chrystelle, Schibler, Laurent, Jammes, Hélène, Kiefer, Hélène, French National Research Agency, French Ministry of Higher Education, Perrier, Jean-Philippe, Sellem, Eli, Prézelin, Audrey, Gasselin, Maxime, Jouneau, Luc, Piumi, François, Adhami, Hala Al, Weber, Michaël, Fritz, Sébastien, Boichard, Didier, Le Danvic, Chrystelle, Schibler, Laurent, Jammes, Hélène, and Kiefer, Hélène
- Abstract
peer-reviewed, Background: Spermatozoa have a remarkable epigenome in line with their degree of specialization, their unique nature and different requirements for successful fertilization. Accordingly, perturbations in the establishment of DNA methylation patterns during male germ cell differentiation have been associated with infertility in several species.Background: Spermatozoa have a remarkable epigenResults: The quantification of DNA methylation at CCGG sites using luminometric methylation assay (LUMA) highlighted the undermethylation of bull sperm compared to the sperm of rams, stallions, mice, goats and men. Total blood cells displayed a similarly high level of methylation in bulls and rams, suggesting that undermethylation of the bovine genome was specific to sperm. Annotation of CCGG sites in different species revealed no striking bias in the distribution of genome features targeted by LUMA that could explain undermethylation of bull sperm. To map DNA methylation at a genome-wide scale, bull sperm was compared with bovine liver, fibroblasts and monocytes using reduced representation bisulfite sequencing (RRBS) and immunoprecipitation of methylated DNA followed by microarray hybridization (MeDIP-chip). These two methods exhibited differences in terms of genome coverage, and consistently, two independent sets of sequences differentially methylated in sperm and somatic cells were identified for RRBS and MeDIP-chip. Remarkably, in the two sets most of the differentially methylated sequences were hypomethylated in sperm. In agreement with previous studies in other species, the sequences that were specifically hypomethylated in bull sperm targeted processes relevant to the germline differentiation program (piRNA metabolism, meiosis, spermatogenesis) and sperm functions (cell adhesion, fertilization), as well as satellites and rDNA repeats. Conclusions: These results highlight the undermethylation of bull spermatozoa when compared with both bovine somatic cells and the sperm of
3. Autoantibodies against type I IFNs in patients with critical influenza pneumonia
- Author
-
Zhang, Qian, Pizzorno, Andrés, Miorin, Lisa, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Bizien, Lucy, Manry, Jeremy, Rosain, Jérémie, Philippot, Quentin, Goavec, Kelian, Wroblewski, Isabelle, Husebye, Eystein, Fellay, Jacques, Pothier, Pierre, Morand, Patrice, Navarrete, Nicolás, Franco, José Luis, Uddin, Mohammed J., Carratalà, Jordi, Merino Díaz, Laura, Palomo, Virginia, Seppänen, Mikko R.J., Särekannu, Karita, Aiuti, Alessandro, Retamar Gentil, Pilar, Debette, Stéphanie, Belot, Alexandre, Abel, Laurent, Soler Palacín, Pere, Abad Arranz, Maria, Aguilar Guisado, Manuela, Meyts, Isabelle, Casanova, Jean-Laurent, Gonzalez Granado, Luis L., Butte, Manish J., Itan, Yuval, Escoresca Ortega, Ana, Morio, Tomohiro, Padey, Blandine, Niubó, Jordi, Gallardo Ríos, Rafaela, Lau, Yu-lung, Triantafyllia, Vasiliki, Briones, Marisa, Saker, Kahina, Richard, Pascale, Drolet, Beth A., Espinosa Padilla, Sara, Wauters, Joost, Peigue Lafeuille, Helene, Valiente, Adoración, El Baghdadi, Jamila, Tiberghien, Pierre, Balsera-manzanero, María, Zins, Marie, Hammarström, Lennart, Andreakos, Evangelos, Notarangelo, Luigi D., Prando, Carolina, Condino-neto, Antonio, Dominguez Pinilla, Nerea, Aydillo, Teresa, Okamoto, Keisuke, Soumaré, Aïcha, Karamitros, Timokratis, Medina, Rafael A., Kisand, Kai, Ramírez Duque, Nieves, Feys, Simon, Romero Oraa, Laura, Kuo, Chen-yen, Lei, Wei-te, Quintana Murci, Lluis, Milner, Joshua D., Ku, Cheng-lung, Van De Beek, Diederik, Hsieh, Elena W.Y., Tal, Galit, Fournet, Thomas, Cerba Healthcare Group, Patural, Hugues, Novelli, Giuseppe, Lyon Antigrippe Working Group, Arias, Andrés A., Rovina, Nikoletta, Rodríguez-gallego, Carlos, Puel, Anne, Jouanguy, Emmanuelle, Vinh, Donald C., Henny, Joseph, Mogensen, Trine H., Cobat, Aurélie, Casari, Giorgio, Ramaswamy, Sathishkumar, Abelenda Alonso, Gabriela, Morel, Pascal, Trouillet Assant, Sophie, Tzourio, Christophe, Gallian, Pierre, Reipi Inf Working Group, García Sastre, Adolfo, Constantinescu, Stefan N., Hamzeh Cognasse, Hind, Haerynck, Filomeen, Flores, Carlos, Bousfiha, Ahmed A., García Salum, Tamara, Shahrooei, Mohammed, Slaby, Ondrej, Fragkou, Paraskevi C., Argaud, Laurent, Shcherbina, Anna, Al-muhsen, Saleh, Biggs, Catherine M., Bogunovic, Dusan, Planas, Anna M., Heath, James R., Von Bernuth, Horst, Dufouil, Carole, Bolze, Alexandre, Boeuf, Benoit, Rodríguez Gallego, Carlos, Christodoulou, John, Bondarenko, Anastasiia, Martin, Fernando, Koltsida, Ourania, Sediva, Anna, Ruiz Hernandez, José Juan, Bonneaudeau, Brigitte, Cannet, Dorothée, Etablissement Français Du Sang Study Group, Froidure, Antoine, Laurent, Emilie, Galani, Ioanna Evdokia, Gregersen, Peter K., Lemonnier, Sylvie, Spaan, András N., Darmon, Michael, Grimbacher, Bodo, Del Mar Muñoz Garcia, Maria, Zawadzki, Pawel, Henrickson, Sarah E., O'farrelly, Cliona, Rosa Calatrava, Manuel, Lachaize, Morgane, Okada, Satoshi, Vanker, Martti, Bryceson, Yenan, Ling, Yun, Cooper, Megan A., Lucas, Carrie L., Maniatis, Tom, Romero Vázquez, Gloria María, Mansouri, Davood, Castagnoli, Riccardo, Maródi, László, Mironska, Kristina, Rapti, Vasiliki, Baris Feldman, Hagit, Pozzetto, Bruno, Renia, Laurent, Tancevski, Ivan, Imai, Kohsuke, Ozcelik, Tayfun, Pan-hammarström, Qiang, Al-mulla, Fahd, Pape, Jean W., Etzioni, Amos, Souweine, Bertrand, Perez De Diego, Rebeca, Sánchez Cordero, Maria Jose, Solé Violán, Jordi, Perlin, David S., Queromes, Gregory, Anderson, Mark S., Resnick, Igor, Pesole, Graziano, Su, Helen C., Vanderbeke, Lore, Hagin, David, Jeanne, Michel, Desai, Murkesh, Ferres, Marcela, Sánchez Céspedes, Javier, Perroquin, Magali, Ng, Lisa F.P., Abou Tayoun, Ahmad, Le Corre, Nicole, Snow, Andrew L., Temel, Şehime Gülsün, Tsiodras, Sotirios, Coeuret Pellicer, Mireille, Javouhey, Etienne, Turvey, Stuart E., Covid Human Genetic Effort, Rombauts, Alexander, Zatz, Mayana, Uddin, K.m. Furkan, Fievet, Nathalie, Jarvis, Erich D., Rodríguez De Castro, Felipe, Ferreres, José, Flaig, Amandine, Pujol, Aurora, Cognasse, Fabrice, Sancho Shimizu, Vanessa, Nadif, Rachel, Hanna, Suhair, Constances Cohort, Goldberg, Marcel, Brodin, Petter, Le Got, Stéphane, Ozguler, Anna, Quenot, Jean Pierre, Novelli, Antonio, Cordero, Elisa, Colomb, Benoit, Cupic, Anastasija, Mehlal Sedkaoui, Souad, Sallette, Jérôme, Hernu, Romain, Bustamante, Carlos D., Lina, Bruno, Halwani, Rabih, Casalegno, Jean Sebastien, Schwebel, Carole, Salamanca Rivera, Celia, 3C-Dijon Study, Tangye, Stuart G., Dalgard, Clifton L., Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Agence Nationale de la Recherche (France), European Commission, Square Foundation, Ministre de l'Enseignement Supérieur, de la Recherche et de l'Innovation (France), Institut National de la Santé et de la Recherche Médicale (France), Université Paris Cité, Center for Research for Influenza Pathogenesis (US), National Institute of Allergy and Infectious Diseases (US), Center of Excellence for Influenza Research and Response (US) CEIRR, Agencia Nacional de Investigación y Desarrollo (Chile), Centre National de la Recherche Scientifique (France), Ministère des Solidarités et de la Santé (France), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundación Mapfre, Sociedad Española de Neumología y Cirugía Torácica, Cabildo de Tenerife, Hellenic Foundation for Research and Innovation, Fondation pour la Recherche Médicale, Fondation Bettencourt Schueller, Ministerio de Ciencia, Innovación y Universidades (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Junta de Andalucía, Research Foundation - Flanders, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 01057100, HORIZON-HLTH-2021-DISEASE-04, MESRI-COVID-19, ANR-10-LABX-62-IBEID, P18-RT-3320, CGIEU0000219140, RTC-2017-6471-1, REIPI RD16/0016/0009, National Institutes of Health, NIH: R01AI088364, R01AI163029, Howard Hughes Medical Institute, HHMI, National Institute of Allergy and Infectious Diseases, NIAID: 75N93021C00014, U19AI135972, U19AI142733, U19AI168631, Jeffrey Modell Foundation, JMF, Glenn Foundation for Medical Research, GFMR: ANRS-COV05, EA20170638020, EQU201903007798, Pfizer, Albert Ellis Institute, AEI, National Center for Advancing Translational Sciences, NCATS: UL1 TR001866, JPB Foundation, JPBF, Horizon 2020 Framework Programme, H2020: 824110, Fondation du Souffle, FdS, College of Natural Resources and Sciences, Humboldt State University, CNRS, Ministerio de Ciencia, Innovación y Universidades, MCIU, Instituto Tecnológico y de Energías Renovables, ITER, SCOR Corporate Foundation for Science, Agence Nationale de la Recherche, ANR: ANR-10-IAHU-01, Institut National de la Santé et de la Recherche Médicale, Inserm, Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT: 1161971, 1212023, Association Nationale de la Recherche et de la Technologie, ANRT, Fonds Wetenschappelijk Onderzoek, FWO: G0B5120N, G0C8517N, G0E8420N, KU Leuven: C16/18/007, Instituto de Salud Carlos III, ISCIII: COV20_01333, COV20_01334, PI12/01565, European Regional Development Fund, ERDF: CB21/13/00006, University of the East, UE, Hellenic Foundation for Research and Innovation, ΕΛ.ΙΔ.Ε.Κ, Université de Paris, SINOVAC outside the submitted work. P. Retamar-Gentil reported personal fees from Merck outside the submitted work. I. Meyts reported grants from CSL-Behring outside the submitted work. E. Andreakos reported grants from Janssen Pharmaceuticals during the conduct of the study. J. Wauters reported grants and personal fees from Pfizer and Gilead outside the submitted work. L. Vanderbeke reported grants from Research Foundation Flanders and non-financial support from Pfizer outside the submitted work. S. Feys reported grants from Pfizer outside the submitted work. J. Casalegno reported 'other' from Pfizer and grants from Sanofi outside the submitted work. M. Rosa-Calatrava reported a patent to WO2016/146836 licensed (Signia Therapeutics), a patent to WO2017/174593 licensed (Signia Therapeutics), and a patent to WO2019/224489 licensed (Signia Therapeutics), and is the co-founder of Signia Therapeutics SAS. S. Trouillet-Assant reported non-financial support from BioMérieux outside the submitted work. A. Garcia-Sastre reported 'other' from Vivaldi Biosciences, Pagoda, Contrafect, Vaxalto, Accurius, Curelab oncology, and Curelab veterinary, personal fees from Avimex, 7Hills, Esperovax, Pfizer, Farmak, Applied Biological Laboratories, Paratus, Pharmamar, Pfizer, and Synairgen, grants from Pfizer, Pharmamar, Blade Therapeutics, Avimex, Accurius, Dyna-vax, Kenall Manufacturing, ImmunityBio, Nanocomposix, Merck, Model Medicines, Atea Pharma, Shenwa Biosciences, Johnson & Johnson, 7 Hills, Hexamer, N-fold LLC, and Applied Biological Laboratories outside the submitted work, in addition, A. Garcia-Sastre had a patent for influenza virus vaccines and uses thereof issued, and invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and Astrazeneca. J. Casanova reported a patent to PCT/US2021/ 042741 pending. No other disclosures were reported., We thank Dr. Cato Jacobs for her contribution to the sampling of UZLeuven patients in Belgium. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH, R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Sci-ence, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmis-sion, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y De-sarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1, AEI/ FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cab-ildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19'). E. Andreakos is supported by the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and In-stituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Regional Development Fund 'A way to achieve Eu-rope', Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University. Author contributions: Q. Zhang, A. Pizzorno, L. Miorin, P., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH, R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmission, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y De-sarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1, AEI/ FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19'). E. Andreakos is supported by the Hellenic Foundation for Research and, Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and In-stituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Regional Development Fund 'A way to achieve Europe', Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University., ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), and ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021)
- Subjects
INTERFERON ,Cerba HealthCare Group ,Immunology ,SEVERE COVID-19 ,Pneumònia ,Autoanticossos ,DETERMINANTS ,IMMUNITY ,Grip ,NEUTRALIZING ANTIBODIES ,3C-Dijon Study ,INFECTION ,Influenza, Human ,Medicine and Health Sciences ,Immunology and Allergy ,Humans ,COVID Human Genetic Effort ,MYASTHENIA-GRAVIS PATIENTS ,Autoantibodies ,REIPI INF Working Group ,Etablissement Français du Sang Study Group ,Yellow Fever Vaccine ,COVID-19 ,Pneumonia ,ALLELES ,Lyon Antigrippe Working Group ,Influenza ,ALPHA ,Settore MED/03 ,Interferon Type I ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,BURDEN ,Constances Cohort - Abstract
Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH; R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmission, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y Desarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19”). E. Andreakos is supported by the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009); cofinanced by European Regional Development Fund “A way to achieve Europe”; Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University.
- Published
- 2022
4. Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium
- Author
-
Pierre Laurent-Puig, Yan Ren, Frédérique Rachédi, Pascal Guénel, Sandya Liyanarachchi, Asta Försti, Albert de la Chapelle, Om Kulkarni, Claire Mulot, Huiling He, Federica Gemignani, Julie Guibon, Anne-Valérie Guizard, Fabienne Lesueur, Rossella Elisei, Ausrele Kesminiene, Anthony F. Herzig, Mojgan Karimi, Pierre-Emmanuel Sugier, Thérèse Truong, Delphine Bacq-Daian, Anne-Louise Leutenegger, Constance Xhaard, Daniel F. Comiskey, Celia M Pereda, Evgenia Ostroumova, Florent de Vathaire, Elisabeth Adjadj, Françoise Borson-Chazot, Jean-François Deleuze, Carole Rubino, Anne Boland-Auge, Hauke Thomsen, Elise A. Lucotte, Marie-Christine Boutron-Ruault, Juan J Lence-Anta, Rosa Ortiz, Claire Schvartz, Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université Paris-Saclay, 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), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Épidémiologie des radiations, épidémiologie clinique des cancers et survie (U1018 (Équipe 3) ), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Institut Jean Godinot [Reims], UNICANCER, Registre Général des Tumeurs du Calvados, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Taaone, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institute of Oncology and Radiobiology, Ohio State University [Columbus] (OSU), University of Pisa - Università di Pisa, Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Hopp Children's Cancer Center Heidelberg [Heidelber, Germany] (KITZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Heidelberg University Hospital [Heidelberg], German Cancer Consortium [Heidelberg] (DKTK), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation, MESRI: 2102 918823 National Institute of Ecology, NIE Agence Nationale de la Recherche, ANR: ANR‐10‐COHO‐0006 Fondation ARC pour la Recherche sur le Cancer, ARC: PGA120150202302 Ligue Contre le Cancer Fondation de France Institut National Du Cancer, INCa: 9533 Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, ANSES Mutuelle Générale de l'Education Nationale, MGEN Electricité de France, EDF: EP 2019‐01, We thank Dr Yannick Rougier and Dr Dominique Baron-Dubourdieu for providing pathological reports for the NC study, as well as Dr Sylvie Laumond, Dr Jean-Paul Grangeon (Direction des affaires sanitaires et sociales de Nouvelle-Cal?donie) and the country's provincial health authorities (DPASS Sud, DPASS Nord, DPASS Iles Loyaut?) for support during data collection in the NC study. We thank Milagros Velasco, Mae Chappe and Idalmis Infante (Institute of Oncology and Radiobiology, La Havana, Cuba) and Silvia Turcios (National Institute of Endocrinology, La Havana, Cuba) for helping in the collection of the data in the Cuban Study. We thank John Paoaafaite and Joseph Teuri who contacted and interviewed cases and controls for the study. Finally, we also thank P. Morales, J. Iltis, P. Giraud, P. Didiergeorge, M. Brisard, G. Soubiran, B. Caillou, P. Dupire, J. Ienfa, G. de Clermont, N. Cerf, B. Oddo, M. Bambridge, C. Baron, A. Mouchard-Rachet, O. Simonet, D. Lamarque, J. Vabret, J. Delacre, M.P. Darquier and J. Leninger, for their help in the collection of the cases or in the organization of study in French Polynesia. We would like to thank the Association Centre de Regroupement Informatique et Statistique en Anatomie Pathologique en Provence-Alpes-C?te d'Azur (CRISAP PACA), as well as Dr Arlette Danzon, Dr Genevi?ve Sasolas, Dr Marc Christophe Sattonnet, Dr Marc Colonna, Dr Brigitte Lacour, Dr Michel Velten, Dr Enora Clero, Dr St?phane Maillard, Dr Laurent Bailly, Dr Eug?nia Marin? Barjoan, Dr Jean-Luc Lassalle, Dr Z Hafdi-Nejjari, Dr P Delafosse, Dr Elisabeth Adjadj, Kami-Marie Moreau, Cyrielle Orenes, Laurianne Sarrazin, St?phanie Bonnay, Fr?d?rique Chatelain, Maryse Barouh, Evelyne Rapp, Julie Festra?ts, Julie Valbousquet, Yusuf Atilgan, Jean Chappellet, Lallia Bedhouche, Florent Dayet and Ziyan Fami, for their help in the collection of cases, the organization and the management of the Young-Thyr study. We acknowledge Stefano Landi for the Italian GWAS data and Subhayan Chattopadhyay and Yasmeen Niazi (Division of Molecular Genetic Epidemiology, German Cancer Research Center?DKFZ) for technical assistance in these data analysis. We are grateful to Dr Herv? Perdry for his help in using the GASTON package. The EPITHYR GWAS was supported by Institut National du Cancer (grant number 9533) and Fondation ARC (grant number PGA120150202302). The E3N cohort received support from the MGEN, Gustave Roussy and Ligue contre le cancer for its setup and maintenance. The E3N cohort was also supported by a state grant from the Agence Nationale pour la Recherche (ANR) (grant number ANR-10-COHO-0006) within the Investissement d'Avenir program and from the French Ministry of Higher Education, Research and Innovation (MESRI, grant number 2102 918823). The other participating studies were funded by Ligue Nationale Contre le Cancer, ANR, the Direction G?n?rale de la Sante, the Agence Fran?aise de S?curit? Sanitaire de l'alimentation, de l'environnement et du travail (ANSES), CHILDTHYR EEC program, and the Fondation de France. JG was the recipient of a PhD fellowship from R?gion Ile-de-France, part of OK was the recipient of a post-doc fellowship from Electricit? de France (conseil scientifique de Radioprotection d'EDF, grant EP 2019-01)., The EPITHYR GWAS was supported by Institut National du Cancer (grant number 9533) and Fondation ARC (grant number PGA120150202302). The E3N cohort received support from the MGEN, Gustave Roussy and Ligue contre le cancer for its setup and maintenance. The E3N cohort was also supported by a state grant from the Agence Nationale pour la Recherche (ANR) (grant number ANR‐10‐COHO‐0006) within the Investissement d'Avenir program and from the French Ministry of Higher Education, Research and Innovation (MESRI, grant number 2102 918823). The other participating studies were funded by Ligue Nationale Contre le Cancer, the Direction Générale de la Sante, the Agence Française de Sécurité Sanitaire de l'alimentation, and the Fondation de France. JG was the recipient of a PhD fellowship from Région Ile‐de‐France, part of OK was the recipient of a post‐doc fellowship from Electricité de France (conseil scientifique de Radioprotection d'EDF, grant EP 2019‐01)., 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), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
- Subjects
Male ,Cancer Research ,Native Hawaiian or Other Pacific Islander ,[SDV]Life Sciences [q-bio] ,Ethnic group ,Genome-wide association study ,0302 clinical medicine ,Gene Frequency ,Informed consent ,Epidemiology ,thyroid cancer ,Chromosomes, Human ,Medicine ,Prospective cohort study ,Thyroid cancer ,Genetics ,0303 health sciences ,education.field_of_study ,Incidence (epidemiology) ,Middle Aged ,Checklist ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,Pacific islanders ,Female ,Adult ,medicine.medical_specialty ,case-control study ,education ,Population ,Biology ,Pacific Islands ,Polymorphism, Single Nucleotide ,White People ,03 medical and health sciences ,Humans ,Genetic Predisposition to Disease ,Thyroid Neoplasms ,Aged ,030304 developmental biology ,genome-wide association study ,business.industry ,Case-control study ,medicine.disease ,Clinical trial ,Case-Control Studies ,Family medicine ,business - Abstract
Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. Here, we conducted a genome-wide association study (GWAS) involving 1,554 cases/1,973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from the EPITHYR consortium. Our results confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 (rs334729) and 16q23.2 (rs16950982), which were associated with TSH levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. The frequency of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans and may explain part of the highest DTC incidence observed in Oceanians.Competing Interest StatementThe authors have declared no competing interest.Funding StatementINCA (grant number 9533) and ARC (grant number PGA120150202302), Ligue Nationale Contre le Cancer, Agence Nationale pour la Recherche (ANR), the Direction Generale de la Sante, the Agence Francaise de Securite Sanitaire de l alimentation, de lenvironnement et du travail (ANSES), CHILDTHYR EEC program, and the Fondation de France. JG and CX were the recipient of a PhD fellowship from Region Ile-de-France.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:All participants provided informed consent and each study was approved by their governing ethics committee.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. (Less)
- Published
- 2021
5. Spectral bandits
- Author
-
Kocák, Tomáš, Munos, Rémi, Kveton, Branislav, Agrawal, Shipra, Valko, Michal, École normale supérieure de Lyon (ENS de Lyon), Scool (Scool), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), DeepMind [Paris], Google Research, Columbia University [New York], The research presented in this paper was supported by French Ministry of Higher Education and Research, by European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no270327 (project CompLACS), European CHIST-ERA project DELTA, French Ministry of Higher Education and Research, Inria and Otto-von-GuerickeUniversit¨at Magdeburg associated-team North-European project Allocate, Nord-Pas-deCalais Regional Council, CPER Nord-Pas de Calais/FEDER DATA Advanced data science and technologies 2015-2020, French National Research Agency projects ExTra-Learn (n°ANR-14-CE24-0010-01) and BoB (n°ANR-16-CE23-0003), Intel Corporation, FMJH Program PGMO with the support to this program from CRITEO., ANR-14-CE24-0010,ExTra-Learn,Extraction et transfert de connaissances dans l'apprentissage par renforcement(2014), ANR-16-CE23-0003,BoB,Inférence bayésienne à ressources limitées - données massives et modèles coûteux(2016), and École normale supérieure - Lyon (ENS Lyon)
- Subjects
[STAT.ML]Statistics [stat]/Machine Learning [stat.ML] - Abstract
International audience; Smooth functions on graphs have wide applications in manifold and semi-supervised learning. In this work, we study a bandit problem where the payoffs of arms are smooth on a graph. This framework is suitable for solving online learning problems that involve graphs, such as content-based recommendation. In this problem, each item we can recommend is a node of an undirected graph and its expected rating is similar to the one of its neighbors. The goal is to recommend items that have high expected ratings. We aim for the algorithms where the cumulative regret with respect to the optimal policy would not scale poorly with the number of nodes. In particular, we introduce the notion of an effective dimension, which is small in real-world graphs, and propose three algorithms for solving our problem that scale linearly and sublinearly in this dimension. Our experiments on contentrecommendation problem show that a good estimator of user preferences for thousands of items can be learned from just tens of node evaluations.
- Published
- 2020
6. Anti‐ HIV ‐1 antibodies trigger non‐lytic complement deposition on infected cells
- Author
-
Ludivine Grzelak, Valérie Lorin, Julian Buchrieser, Guillaume Mestrallet, Katia Bourdic, Jérémy Dufloo, Timothée Bruel, Emilie Dupouy, Olivier Schwartz, Olivier Lambotte, Florence Guivel-Benhassine, Hugo Mouquet, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Work in OS laboratory is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), the Labex IBEID (ANR-10-IHUB-0002), the 'TIMTAMDEN' ANR-14-CE14-0029, the 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01, L'Oréal Sponsorship, and the Gilead HIV cure program. HM is supported by the European Research Council (ERC)—Seventh Framework Program (ERC-2013-StG 337146), the G5 Institut Pasteur Program, the Milieu Intérieur Program (ANR-10-LABX-69-01), the INSERM, and the ANRS. JD is supported by a grant from the French Ministry of Higher Education, Research and Innovation., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), European Project: 337146,EC:FP7:ERC,ERC-2013-StG,HUMANTIVIRUSES(2014), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute [Créteil, France] (VRI), Virus et Immunité, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Work in OS laboratory is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR‐10‐LABX‐77), the Labex IBEID (ANR‐10‐IHUB‐0002), the 'TIMTAMDEN' ANR‐14‐CE14‐0029, the 'CHIKV‐Viro‐Immuno' ANR‐14‐CE14‐0015‐01, L'Oréal Sponsorship, and the Gilead HIV cure program. HM is supported by the European Research Council (ERC)—Seventh Framework Program (ERC‐2013‐StG 337146), the G5 Institut Pasteur Program, the Milieu Intérieur Program (ANR‐10‐LABX‐69‐01), the INSERM, and the ANRS. JD is supported by a grant from the French Ministry of Higher Education, Research and Innovation., We thank members of the Virus and Immunity Unit for discussion and help. We thank patients who participated in the study and Cécile Goujard for supervision of the patients’ enrollment. We thank the NIH AIDS Reagent Program for providing reagents. We thank Michel C. Nussenzweig (The Rockefeller University) for providing the pMX‐YU2 ENVΔCT‐GFP‐PuroR expression vector. We thank Frank Kirchhoff and Daniel Sauter (Ulm University) for providing CH058, CH058∆Nef, CH058∆Vpu, and CH058∆Nef∆Vpu plasmids., and ANR-10-LABX-0077/10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010)
- Subjects
[SDV]Life Sciences [q-bio] ,MESH: Complement System Proteins ,HIV Infections ,CD59 ,V3 loop ,HIV Antibodies ,Biochemistry ,MESH: HIV-1 ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,Humans ,complement ,Cytotoxicity ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,MESH: Humans ,biology ,MESH: HIV Antibodies ,broadly neutralizing antibodies ,virus diseases ,Complement System Proteins ,MESH: HIV Infections ,Virology ,3. Good health ,Raji cell ,Complement system ,Lytic cycle ,Polyclonal antibodies ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,biology.protein ,HIV-1 ,Antibody ,030217 neurology & neurosurgery - Abstract
International audience; The effect of anti-HIV-1 antibodies on complement activation at the surface of infected cells remains partly understood. Here, we show that a subset of anti-Envelope (Env) broadly neutralizing antibodies (bNAbs), targeting the CD4 binding site and the V3 loop, triggers C3 deposition and complement-dependent cytotoxicity (CDC) on Raji cells engineered to express high surface levels of HIV-1 Env. Primary CD4 T cells infected with laboratory-adapted or primary HIV-1 strains and treated with bNAbs are susceptible to C3 deposition but not to rapid CDC. The cellular protein CD59 and viral proteins Vpu and Nef protect infected cells from CDC mediated by bNAbs or by polyclonal IgGs from HIV-positive individuals. However, complement deposition accelerates the disappearance of infected cells within a few days of culture. Altogether, our results uncover the contribution of complement to the antiviral activity of anti-HIV-1 bNAbs.
- Published
- 2019
7. MetaTOR: A Computational Pipeline to Recover High-Quality Metagenomic Bins From Mammalian Gut Proximity-Ligation (meta3C) Libraries
- Author
-
Lyam Baudry, Théo Foutel-Rodier, Agnès Thierry, Romain Koszul, Martial Marbouty, Régulation spatiale des Génomes - Spatial Regulation of Genomes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Sorbonne Université (SU), LB is supported by an AMX fellowship from the French Ministry of Higher Education, Research and Innovation. TFR is supported by an ENS fellowship by the French Ministry of Higher Education, Research and Innovation. This research was supported by funding to RK from the European Research Council under the Horizon 2020 Program (ERC grant agreement 260822) and from the Agence Nationale pour la Recherche (JPI-EC-AMR STARCS ANR-16-JPEC-0003-05)., ANR-16-JPEC-0003,STARCS,Selection and Transmission of Antimicrobial Resistance in Complex Systems(2016), European Project: 260822,EC:FP7:ERC,ERC-2010-StG_20091118,DICIG(2011), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,lcsh:QH426-470 ,metagenome-assembled genomes ,Computer science ,[SDV]Life Sciences [q-bio] ,metagenomics Hi-C ,gut microbiome ,Computational biology ,metagenomics binning ,Genome ,DNA sequencing ,Chromosome conformation capture ,03 medical and health sciences ,0302 clinical medicine ,[SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems ,Hi-C ,Genetics ,Genetics (clinical) ,Original Research ,[SDV.EE]Life Sciences [q-bio]/Ecology, environment ,Contig ,metagenomic analysis ,Pipeline (software) ,Gut microbiome ,lcsh:Genetics ,030104 developmental biology ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Metagenomics ,030220 oncology & carcinogenesis ,binning algorithm ,Molecular Medicine - Abstract
International audience; Characterizing the complete genomic structure of complex microbial communities would represent a key step toward the understanding of their diversity, dynamics, and evolution. Current metagenomics approaches aiming at this goal are typically done by analyzing millions of short DNA sequences directly extracted from the environment. New experimental and computational approaches are constantly sought for to improve the analysis and interpretation of such data. We developed MetaTOR, an open-source computational solution that bins DNA contigs into individual genomes according to their 3D contact frequencies. Those contacts are quantified by chromosome conformation capture experiments (3C, Hi-C), also known as proximity-ligation approaches, applied to metagenomics samples (meta3C). MetaTOR was applied on 20 meta3C libraries of mice gut microbiota. We quantified the program ability to recover high-quality metagenome-assembled genomes (MAGs) from metagenomic assemblies generated directly from the meta3C libraries. Whereas nine high-quality MAGs are identified in the 148-Mb assembly generated using a single meta3C library, MetaTOR identifies 82 high-quality MAGs in the 763-Mb assembly generated from the merged 20 meta3C libraries, corresponding to nearly a third of the total assembly. Compared to the hybrid binning softwares MetaBAT or CONCOCT, MetaTOR recovered three times more high-quality MAGs. These results underline the potential of 3C-/Hi-C-based approaches in metagenomic projects.
- Published
- 2019
8. Structural and Radio Frequency Co-Design and Optimization of Large Deployable Reflectarrays for Space Missions
- Author
-
Andrea Guarriello, Renaud Loison, Daniele Bresciani, Hervé Legay, George Goussetis, Institut d'Électronique et des Technologies du numéRique (IETR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Thales Alenia Space [Toulouse] (TAS), THALES [France], Heriot-Watt University [Edinburgh] (HWU), European Commission [MSCA-ITN2016-722840], and French Ministry of Higher Education, Research and Innovation through the 'France Relance' project SOAR [ANR-21-PRRD-0037-01]
- Subjects
Fasteners ,Finite element analysis ,thermoelastic deformation (TED) ,Geometry ,Thermal stability ,Contoured beam ,[SPI]Engineering Sciences [physics] ,satellite antenna ,Thermal loading ,Radio frequency ,Loaded antennas ,phoenix cells ,Electrical and Electronic Engineering ,optimization ,large deployable reflectarray (RA) - Abstract
International audience; The structural and radio frequency (RF) design and optimization of a large deployable faceted reflectarray (RA) generating double polarization contour beam are presented in this work. The issue addressed is the thermoelastic stability of large RAs and the impact of the thermoelastic deformation (TED) under transverse thermal gradient on the RA performances. Finite element TED analysis is conducted on a deployable RA with self-standing structures, demonstrating the detrimental effects of the in-orbit TED impact on the RA performances, estimated to be above 3 dB losses. To this extent, a novel structural solution is proposed, based on the use of reliable mechanical support capable to mitigate the TED. The mechanical design reorientation is contingent on the RF design reformulation. The proposed novel mechanical and RF co-design concept and methodology allows the conception of a low-profile, thermo-structurally stable RA with compliant radiation patterns and high cross-polarization discrimination in the worst case thermal load. This methodology is based on a direct optimization of nine-panel faceted RA composed of advanced high-order Phoenix cells directly optimized to fulfill the contoured beam requirements and by respecting the local periodicity requirements of the layout.
- Published
- 2023
9. The performance of approximate equation of motion coupled cluster for valence and core states of heavy element systems
- Author
-
Halbert, Loïc, Gomes, Andre Severo Pereira, Physico-Chimie Moléculaire Théorique (PCMT), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), French Ministry of Higher Education and Research, region Hauts de France council and European Regional Development Fund (ERDF), Project CPER WAVETECH, French national supercomputing facilities (grants DARI A0090801859, A0110801859), ANR-11-LABX-0005,Cappa,Physiques et Chimie de l'Environnement Atmosphérique(2011), ANR-16-IDEX-0004,ULNE,ULNE(2016), and ANR-19-CE29-0019,CompRIXS,Calcul de la diffusion inélastique résonante de rayons X pour toute la classification périodique(2019)
- Subjects
Chemical Physics (physics.chem-ph) ,[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,Physics - Chemical Physics ,FOS: Physical sciences - Abstract
The equation of motion coupled cluster singles and doubles model (EOM-CCSD) is an accurate, black-box correlated electronic structure approach to investigate electronically excited states and electron attachment or detachment processes. It has also served as a basis for developing less computationally expensive approximate models such as partitioned EOM-CCSD (P-EOM-CCSD), the second-order many-body perturbation theory EOM (EOM-MBPT(2)), and their combination (P-EOM-MBPT(2)) [S. Gwaltney et al., Chem. Phys. Lett. 248, 189-198 (1996)]. In this work we outline an implementation of these approximations for four-component based Hamiltonians and investigate their accuracy relative to EOM-CCSD for valence excitations, valence and core ionizations and electron attachment, and this for a number of systems of atmospheric or astrophysical interest containing elements across the periodic table. We have found that across the different systems and electronic states of different nature considered, partition EOM-CCSD yields results with the largest deviations from the reference, whereas second-order based approaches tend show a generally better agreement with EOM-CCSD. We trace this behavior to the imbalance brought about by the removal of excited state relaxation in the partition approaches, with respect to degree of electron correlation recovered., Comment: 5 figures, 4 tables
- Published
- 2023
10. Protein - ligand interactions from a quantum fragmentation perspective : the case of the SARS-CoV-2 main protease interacting with α−ketoamide inhibitors
- Author
-
Genovese, Luigi, Dawson, William, Nakajima, Takahito, Cristiglio, Viviana, Vallet, Valérie, Masella, Michel, Laboratory of Atomistic Simulation (LSIM), Modélisation et Exploration des Matériaux (MEM), 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 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), RIKEN Center for Computational Science [Kobe] (RIKEN CCS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Institut Laue-Langevin (ILL), Physico-Chimie Moléculaire Théorique (PCMT), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Structurale et Radiobiologie (LBSR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), TGCC HPC resources under the allocation 2019-2020[A0070307078] and the Grand Challenge allocation [GC0429] made by GENCI, MAX EU Center of Excellence, CPER CLIMIBIO (European Regional Development Fund, Hauts de France council, French Ministry of Higher Education and Research), ANR-11-LABX-0005,Cappa,Physiques et Chimie de l'Environnement Atmosphérique(2011), and ANR-16-IDEX-0004,ULNE,ULNE(2016)
- Subjects
[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,[PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph] - Abstract
International audience; We present a hybrid, multi-method, computational scheme for protein/ligand systems well suited to be used on modern and forthcoming massively parallel computing systems. The scheme relies on a multi-scale polarizable Molecular Modeling, MM, approach to perform MD simulations and on an efficient DFT Linear Scaling method to post-process simulation snapshots. We use this scheme to investigate recent α-ketoamide inhibitors targeting the main protease of the SARS-CoV-2 virus. We assessed the reliability and the coherence of the hybrid scheme in particular by checking the ability of MM and DFT to reproduce results from high-end ab initio computations regarding such inhibitors. The DFT approach enables an a posterior fragmentation of the system and an investigation into the strength of interaction among identified fragment pairs.
- Published
- 2023
11. How does bending the uranyl unit influence its spectroscopy and luminescence
- Author
-
Hanna Oher, André Severo Pereira Gomes, Richard E. Wilson, David D. Schnaars, Valérie Vallet, 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), Physico-Chimie Moléculaire Théorique (PCMT), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Chemical Sciences and Engineering Division [Argonne], Argonne National Laboratory [Lemont] (ANL), Deutsche Forschung Gemeinschaft JA 2329/6, I-SITE ULNE projects OVERSEE, I-SITE ULNE MESONM International Associated Laboratory (LAI), French Ministry of Higher Education and Research, Région Hauts de France council and European Regional Development Fund (ERDF) project CPER CLIMIBIO, WaveTech, French national supercomputing facilities (grants DARI A0130801859, A0110801859, U.S. DOE Office of Science, Office of Basic Energy Sciences, Chemical Sciences Geological and Biosciences Division,Heavy Element Chemistry program under Contract DE-AC02-06CH11357, ANR-21-CE29-0027,CHESS,Chimie, spectroscopie et spéciation du protactinium(2021), ANR-19-CE29-0019,CompRIXS,Calcul de la diffusion inélastique résonante de rayons X pour toute la classification périodique(2019), ANR-16-IDEX-0004,ULNE,ULNE(2016), and ANR-11-LABX-0005,Cappa,Physiques et Chimie de l'Environnement Atmosphérique(2011)
- Subjects
[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,[CHIM.INOR]Chemical Sciences/Inorganic chemistry - Abstract
International audience; Bent uranyl complexes can be formed with chloride ligands and 1,10-phenanthroline (phen) ligands bound to the equatorial and axial planes of the uranyl(VI) moiety, as revealed by the crystal structures, IR and Raman spectroscopy and quantum chemical calculations. With the goal of probing the influence of chloride and phenanthroline coordination enforcing the bending on the absorption and emission spectra of this complex, spin-orbit time-dependent density functional theory calculations for the bare uranyl complexes as well as for the free UO2Cl2 subunit and the UO2Cl2(phen)2 ligand were performed. The emission spectra has been fully simulated by ab initio methods and compared to experimental photoluminescence spectra, recorded for the first time for UO2Cl2(phen)2. Notably, the bending of uranyl in UO2Cl2 and UO2Cl2(phen)2 triggers excitations of the uranyl bending mode, yielding a denser luminescence spectrum.
- Published
- 2023
12. Odorant-binding proteins mutants having novel binding properties
- Author
-
Barou, Emilie, Belloir, Christine, Poirier, Nicolas, Neiers, Fabrice, Briand, Loïc, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), 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), The French Ministry for Higher Education and Research, the Regional Council of Burgundy France (PARI Agral 1) and the FEDER (European Funding for Regional Economical Development)., 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), French Ministry for Higher Education and Research Regiona Council of Burgundy France (PARI Agral 1) FEDER (European Funding for Regional Economical Development), European Chemorecept Res Org, 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 ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
- Subjects
Physiology ,[ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition ,Food Science & Technology ,Neurosciences ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Behavioral Sciences ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,ComputingMilieux_MISCELLANEOUS - Abstract
Odorant-binding proteins (OBP) are small soluble proteins present in the nasal mucus covering the olfactory epithelium. Vertebrate OBPs belong to the lipocalin superfamily, whose members share a common scaffold made of 8-stranded β-barrel. This folding pattern defines a central apolar cavity, named calyx, whose role is to bind hydrophobic molecules such as odorants. Although the physiological role of OBPs is not clearly established, they are supposed to carry odorants from the air to olfactory receptors through the aqueous nasal mucus. OBPs have been described in numerous species including pig, rat and human beings. OBPs are broadly tuned and bind a large spectrum of volatile molecules. Interestingly, it has been shown that the three rat OBP subtypes (rOBP1, rOBP2, rOBP3) have different and complementary ligand properties [1], suggesting that OBPs are involved in odorant discrimination. Protein sequence alignment of the three rat OBPs reveals the presence of an amino acid residue located in the binding pocket, which may be important for guiding binding specificity. Using site-directed mutagenesis, we generated variants of rOBP3, in which this amino acid residue has been substituted. Using isothermal titration calorimetry, we found that some substitutions decreased the affinity of rOBP3 towards some odorant molecules while others generated OBPs possessing novel binding properties. Our work gives new elements to understand the binding mechanisms of OBPs and opens the way towards technological applications based on OBP, as odorant biosensors. [1] D. Löbel, M. Jacob, M. Volkner, H. Breer, Odorants of different chemical classes interact with distinct odorant binding protein subtypes, Chem. Senses, 27 (2002) 39-44.
- Published
- 2016
13. Complex 4q35 and 10q26 Rearrangements
- Author
-
Delourme, Megane, Charlene, Chaix, Gerard, Laurene, Ganne, Benjamin, Perrin, Pierre, Vovan, Catherine, Bertaux, Karine, Nguyen, Karine, Bernard, Rafaelle, Magdinier, Frederique, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Association Française contre les Myopathies (AFM-Telethon, TRIM-RD and MoThARD poles)French Ministry of Higher education and Research
- Subjects
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,[SDV]Life Sciences [q-bio] ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Background and Objectives After clinical evaluation, the molecular diagnosis of type 1 facioscapulohumeral dystrophy (FSHD1) relies in most laboratories on the detection of a shortened D4Z4 array at the 4q35 locus by Southern blotting. In many instances, this molecular diagnosis remains inconclusive and requires additional experiments to determine the number of D4Z4 units or identify somatic mosaicism, 4q-10q translocations, and proximal p13E-11 deletions. These limitations highlight the need for alternative methodologies, illustrated by the recent emergence of novel technologies such as molecular combing (MC), single molecule optical mapping (SMOM), or Oxford Nanopore-based long-read sequencing providing a more comprehensive analysis of 4q and 10q loci. Over the last decade, MC revealed a further increasing complexity in the organization of the 4q and 10q distal regions in patients with FSHD with cis -duplication of D4Z4 arrays in approximately 1%–2% of cases. Methods By using MC, we investigated in our center 2,363 cases for molecular diagnosis of FSHD. We also evaluated whether previously reported cis -duplications might be identified by SMOM using the Bionano EnFocus FSHD 1.0 algorithm. Results In our cohort of 2,363 samples, we identified 147 individuals carrying an atypical organization of the 4q35 or 10q26 loci. Mosaicism is the most frequent category followed by cis -duplications of the D4Z4 array. We report here chromosomal abnormalities of the 4q35 or 10q26 loci in 54 patients clinically described as FSHD, which are not present in the healthy population. In one-third of the 54 patients, these rearrangements are the only genetic defect suggesting that they might be causative of the disease. By analyzing DNA samples from 3 patients carrying a complex rearrangement of the 4q35 region, we further showed that the SMOM direct assembly of the 4q and 10q alleles failed to reveal these abnormalities and lead to negative results for FSHD molecular diagnosis. Discussion This work further highlights the complexity of the 4q and 10q subtelomeric regions and the need of in-depth analyses in a significant number of cases. This work also highlights the complexity of the 4q35 region and interpretation issues with consequences on the molecular diagnosis of patients or genetic counseling.
- Published
- 2023
14. Chromosome folding and prophage activation reveal specific genomic architecture for intestinal bacteria
- Author
-
Lamy-Besnier, Quentin, Bignaud, Amaury, Garneau, Julian, Titecat, Marie, Conti, Devon, von Strempel, Alexandra, Monot, Marc, Stecher, Bärbel, Koszul, Romain, Debarbieux, Laurent, Marbouty, Martial, Bactériophage, bactérie, hôte - Bacteriophage, bacterium, host, 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), Régulation spatiale des Génomes - Spatial Regulation of Genomes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), Biomics (plateforme technologique), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Max Von Pettenkofer Institute (MVP), Ludwig-Maximilians-Universität München (LMU), German Center for Infection Research, Partnersite Munich (DZIF), This research was supported by funding to BS from DFG-STE-1971/11–1 (PhaStGut project), to BS from the European Research Council under the Horizon 2020 Program (ERC grant agreement 865615), to LD and MMa from PRCI ANR-20-CE92-0048 (PhaStGut project), and to RK from the European Research Council under the Horizon 2020 Program (ERC grant agreement 771813) and from JPI-EC-AMR STARCS ANR-16-JPEC-0003–05. QLB received funding from École Doctorale FIRE-Program Bettencourt. AB is supported by an ENS fellowship from the French Ministry of Higher Education, Research and Innovation. MMo and JRG were supported by JCJC ANR-18-CE35-0011 (project CDPhages). MT received funding from DigestScience. Biomics Platform, C2RT, Institut Pasteur, Paris, France, was supported by France Génomique (ANR-10-INBS-09) and IBISA. AB and DC belong to Ecole Doctorale Complexité du vivant ED515 of Sorbonne Université., ANR-20-CE92-0048,PhaStGut,Etude des mécanismes de la coexistence stable entre bactériophages et bactéries et de ses conséquences sur la fonction du microbiote intestinal(2020), ANR-16-JPEC-0003,STARCS,Selection and Transmission of Antimicrobial Resistance in Complex Systems(2016), ANR-18-CE35-0011,CDPhages,Le role des bactériophages dans l'évolution de la virulence chez Clostridium difficile(2018), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), and European Project: 771813,ERC-2017-COG,SynarchiC(2018)
- Subjects
Microbiology (medical) ,MESH: Humans ,Virome ,MESH: Genomics ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,OMM12 ,Phages Gut HiC Virome OMM12 3D signatures ,Microbiology ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,MESH: Bacteria ,MESH: Prophages ,3D signatures ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Phages ,Gut ,MESH: Animals ,MESH: Ecosystem ,MESH: Chromosomes ,MESH: Bacteriophages ,HiC ,MESH: Mice - Abstract
Background Bacteria and their viruses, bacteriophages, are the most abundant entities of the gut microbiota, a complex community of microorganisms associated with human health and disease. In this ecosystem, the interactions between these two key components are still largely unknown. In particular, the impact of the gut environment on bacteria and their associated prophages is yet to be deciphered. Results To gain insight into the activity of lysogenic bacteriophages within the context of their host genomes, we performed proximity ligation-based sequencing (Hi-C) in both in vitro and in vivo conditions on the 12 bacterial strains of the OMM12 synthetic bacterial community stably associated within mice gut (gnotobiotic mouse line OMM12). High-resolution contact maps of the chromosome 3D organization of the bacterial genomes revealed a wide diversity of architectures, differences between environments, and an overall stability over time in the gut of mice. The DNA contacts pointed at 3D signatures of prophages leading to 16 of them being predicted as functional. We also identified circularization signals and observed different 3D patterns between in vitro and in vivo conditions. Concurrent virome analysis showed that 11 of these prophages produced viral particles and that OMM12 mice do not carry other intestinal viruses. Conclusions The precise identification by Hi-C of functional and active prophages within bacterial communities will unlock the study of interactions between bacteriophages and bacteria across conditions (healthy vs disease).
- Published
- 2023
15. Type I interferons and SARS-CoV-2: from cells to organisms
- Author
-
Paul Bastard, Qian Zhang, Shen-Ying Zhang, Emmanuelle Jouanguy, Jean-Laurent Casanova, Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the ‘Investments for the Future’ program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation programme under grant agreement No 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarite ́pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, Institut National de la Sante ́ et de la Recherche Me ́ dicale (INSERM), the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), REACTing-INSERM and the University of Paris. PB was supported by the French Foundation for Medical Research (FRM, EA20170638020). PB was supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller)., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), Université Paris Cité, Equipe HAL, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères - - GENVIR2020 - ANR-20-CE93-0003 - AAPG2020 - VALID, Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant. - - GenMIS-C2021 - ANR-21-COVR-0039 - COVID-19 - VALID, and Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19. - - AABIFNCOV2020 - ANR-20-CO11-0001 - COVID-19 - VALID
- Subjects
MESH: Interferon Type I ,MESH: Humans ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,SARS-CoV-2 ,Immunology ,COVID-19 ,Article ,Interferon Type I ,MESH: COVID-19 ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Animals ,Humans ,Immunology and Allergy ,MESH: Animals ,MESH: SARS-CoV-2 - Abstract
International audience; Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type I IFNs and SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of type I IFNs, and SARS-CoV-2 proteins can inhibit various steps in type I IFN production and response. Exogenous type I IFNs inhibit viral growth in vitro. In various animal species infected in vivo, type I IFN deficiencies underlie higher viral loads and more severe disease than in control animals. The early administration of exogenous type I IFNs improves infection control. In humans, inborn errors of, and auto-antibodies against type I IFNs underlie life-threatening COVID-19 pneumonia. Overall, type I IFNs are essential for host defense against SARS-CoV-2 in individual cells and whole organisms.
- Published
- 2022
16. Modeling environment effect on heavy-element compounds
- Author
-
Olejniczak, Małgorzata, Vallet, Valérie, Severo Pereira Gomes, André, Centre of New Technologies, Medical University of Warsaw - Poland, Physico-Chimie Moléculaire Théorique (PCMT), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), he French Ministry of Higher Education and Research, region Hauts de France council and European Regional Development Fund (ERDF) projects CPER CLIMIBIO and WAVETECH, Deutsche Forschungsgemeinschaft JA 2329/6-1, Polish National Science Centre (NCN) (grantnumber 2020/38/E/ST4/00614, ANR-16-IDEX-0004,ULNE,ULNE(2016), ANR-11-LABX-0005,Cappa,Physiques et Chimie de l'Environnement Atmosphérique(2011), ANR-21-CE29-0027,CHESS,Chimie, spectroscopie et spéciation du protactinium(2021), and ANR-19-CE29-0019,CompRIXS,Calcul de la diffusion inélastique résonante de rayons X pour toute la classification périodique(2019)
- Subjects
[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry - Abstract
Modeling the behavior of molecular complexes containing one or more heavy elements by means of electronic structure calculations, in particular when attempting to understand their molecular properties, is a very challenging task since one has to account not only for electron correlation and relativistic effects but in many cases consider the effect of other species in their vicinity as well. In this chapter, we address how such environment effects can be taken into account in a computationally efficient manner through different flavors of so-called embedding theories, underscoring the applicability, strengths, and weaknesses of the most commonly used approaches.
- Published
- 2023
17. Transition Moments Beyond the Electric-Dipole Approximation: Visualization and Basis Set Requirements
- Author
-
Martin van Horn, Nanna Holmgaard List, Trond Saue, Laboratoire de Chimie et Physique Quantiques Laboratoire (LCPQ), 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)-Fédération de recherche « Matière et interactions » (FeRMI), 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)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Royal Institute of Technology [Stockholm] (KTH ), French Ministry of Higher Education and Research, CALMIP (Calcul en Midi-Pyrenées, project P13154), SNIC (Swedish National Infrastructure for Computing, and SNIC 2022/5-220)
- Subjects
[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,General Physics and Astronomy ,Physical and Theoretical Chemistry - Abstract
In the simulation of X-ray absorption spectroscopy, the validity of the electric dipole approximation comes into question. Three different schemes exist to go beyond thisapproximation: the first scheme is based on the full semi-classical light-matter inter-action, whereas the latter two schemes, referred to as the generalized length and velocity representation, are based on truncated multipole expansions. Even though these schemes have been successfully implemented in several quantum chemistry codes,their basis set requirements remained largely unknown. Here, we assess the basis set requirements of the full interaction operator and the generalized length and velocity representations. These three schemes were applied in the calculation of radial distributions of transition moment densities corresponding to the 1s1/2 and 7s1/2 7p1/2transition in the radium atom, representative of core and valence excitations, respectively. We have performed calculations with the dyall.aeXz (X=2,3,4) basis sets at the four-component relativistic TD-HF level of theory and compared them withequivalent finite-difference calculations. We find that the full interaction is extremelystable with respect to the choice of basis set, already being converged with dyall.ae2z.With respect to truncated interaction, we find that the length representation electric multipoles is the easiest to converge, requiring the dyall.ae2z basis for low-order multipoles and the dyall.ae4z basis at higher orders. The magnetic multipole moments follow a similar trend, although they are more diffcult to converge. The velocity representation electric multipoles are the most difficult to converge: at high orders, thedyall.ae3z and dyall.ae4z basis sets introduce artificial peaks and oscillations, which increase the overall error. These artifacts are associated with linear dependence issues in the small component space of the larger basis sets. The full interaction operator,however, does not suffer from these problems, and we therefore recommend its use in the simulation of x-ray spectroscopy.
- Published
- 2023
18. Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria
- Author
-
Jérémie Rosain, Anna-Lena Neehus, Jérémy Manry, Rui Yang, Jérémie Le Pen, Wassim Daher, Zhiyong Liu, Yi-Hao Chan, Natalia Tahuil, Özden Türel, Mathieu Bourgey, Masato Ogishi, Jean-Marc Doisne, Helena M. Izquierdo, Takayoshi Shirasaki, Tom Le Voyer, Antoine Guérin, Paul Bastard, Marcela Moncada-Vélez, Ji Eun Han, Taushif Khan, Franck Rapaport, Seon-Hui Hong, Andrew Cheung, Kathrin Haake, Barbara C. Mindt, Laura Pérez, Quentin Philippot, Danyel Lee, Peng Zhang, Darawan Rinchai, Fatima Al Ali, Manar Mahmoud Ahmad Ata, Mahbuba Rahman, Jessica N. Peel, Søren Heissel, Henrik Molina, Yasemin Kendir-Demirkol, Rasheed Bailey, Shuxiang Zhao, Jonathan Bohlen, Mathieu Mancini, Yoann Seeleuthner, Marie Roelens, Lazaro Lorenzo, Camille Soudée, María Elvira Josefina Paz, María Laura González, Mohamed Jeljeli, Jean Soulier, Serge Romana, Anne-Sophie L’Honneur, Marie Materna, Rubén Martínez-Barricarte, Mathieu Pochon, Carmen Oleaga-Quintas, Alexandre Michev, Mélanie Migaud, Romain Lévy, Marie-Alexandra Alyanakian, Flore Rozenberg, Carys A. Croft, Guillaume Vogt, Jean-François Emile, Laurent Kremer, Cindy S. Ma, Jörg H. Fritz, Stanley M. Lemon, András N. Spaan, Nicolas Manel, Laurent Abel, Margaret R. MacDonald, Stéphanie Boisson-Dupuis, Nico Marr, Stuart G. Tangye, James P. Di Santo, Qian Zhang, Shen-Ying Zhang, Charles M. Rice, Vivien Béziat, Nico Lachmann, David Langlais, Jean-Laurent Casanova, Philippe Gros, Jacinta Bustamante, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hannover Medical School [Hannover] (MHH), St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Institut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Yong Loo Lin School of Medicine [Singapore], Hospital del Niño Jesus, San Miguel de Tucumán, Bezmiâlem Vakıf Üniversitesi, McGill University = Université McGill [Montréal, Canada], Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Curie [Paris], University of North Carolina System (UNC), Garvan Institute of medical research, The University of Sydney, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universidad de Antioquia = University of Antioquia [Medellín, Colombia], East China Normal University [Shangaï] (ECNU), Sidra Medicine [Doha, Qatar], 'Juan Pedro Garrahan' National Hospital of Pediatrics, Buenos Aires, 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), Hôpital Cochin [AP-HP], Hopital Saint-Louis [AP-HP] (AP-HP), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Hôpital Ambroise Paré [AP-HP], Université de Montpellier (UM), Howard Hughes Medical Institute (HHMI), The Laboratory of Human Genetics of Infectious Diseases is supported in part by grants from Inserm, Paris Cité University, the St. Giles Foundation, The Rockefeller University, the Center for Clinical and Translational Science (UL1TR001866), the National Center for Research Resources and the National Center for Advancing Sciences, the National Institutes of Health (NIH), (R01AI095983, R01AI088364, R01AI163029, and U19AI162568), the National Institute of Allergy and Infectious Diseases, the French National Research Agency (ANR) under the 'Investments for the future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS Nord-Sud (ANRS-COV05), ANRS (ECTZ170784-ANRS0073), GENVIR (ANR-20-CE93-003), GENMSMD (ANR-16-CE17-0005-01), AABIFNCOV (ANR-20-CO11-0001), GenMIS-C (ANR-21-COVR-0039), SUNLIVE (ANR-19-CE15-0012-01), MAFMACRO (ANR-22-CE92-0008) grants, Ecos-NORD (ECOS N°C19S01), the Fisher Center for Alzheimer's Research Foundation, the Meyer Foundation, the JPB Foundation, the European Union’s Horizon 2020 research and innovation program (824110, EASI-Genomics), the Square Foundation, Grandir–Fonds de solidarité pour l’Enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), and REACTing-INSERM. The Laboratory of Virology and Infectious Disease was supported in part by the NIH (R01AI091707-10 to C.M.R.). J.L.P. was supported by the Francois Wallace Monahan Postdoctoral Fellowship at The Rockefeller University and the European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018). N. Marr was supported by Sidra Medicine and the Qatar National Research Fund (NPRP9-251-3-045). The Yale Center for Mendelian Genomics (UM1HG006504) was funded by the National Human Genome Research Institute, the Yale GSP Coordinating Center (U24 HG008956), and the Yale High-Performance Computing Center (S10OD018521). This research was partly supported by Calcul Québec, Compute Canada Canadian Institutes of Health Research (CIHR) Project Grant to D. Langlais. (#168959) and a CIHR Foundation Grant (to P.G.). D. Langlais was also supported by an FRQS Chercheur-Boursier Junior 1 Award and the Calgary Foundation for Innovation John R. Evans Leaders Fund. P.G. is supported by a Distinguished James McGill Professorship award from McGill University. S.M.L is supported by the NIH: R01-AI103083 and R01-AI150095. J.R. was supported by poste d’accueil Inserm'. J.R., P.B., and T.L.V were supported by the MD-PhD program of the Imagine Institute by the Bettencourt Schueller Foundation. N.L received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (852178 grant), German Research Foundation,(DFG) under Germany’s Excellence Strategy—EXC 2155—project number 390874280 and REBIRTH 'Förderung aus Mitteln des Niedersächsischen Vorab'. A.-L.N. was supported by the international PhD program of the Imagine Institute, by the Bettencourt Schueller Foundation and the fin de thèse FRM program (FDT202204015102). R.Y. was supported by the Sackler Center for Biomedicine and Nutrition, the Shapiro-Silverberg Fund for the Advancement of Translational Research at the Center for Clinical and Translational Science of the Rockefeller University, and the Research Grant Program from the Immune Deficiency Foundation. D. Lee. was supported by FRMfellowship (FDM202006011282). C.S.M was supported by an Early-Mid Career Research Fellowship from the Department of Health of the New South Wales Government of Australia. S.G.T was supported by an NHMRC Leadership 3 Investigator Grant (1176665) and NHMRC grant (1113904). M.O. was supported by the David Rockefeller Graduate Program, the Funai Foundation for Information Technology, the Honjo International Scholarship Foundation, and the New York Hideyo Noguchi Memorial Society. This work was supported by grants from ANRS (ECTZ118797), Sidaction (20-2-AEQ-12822-2), and FRM (EQU202103012774) to N. Manel, and H.I. was supported by fellowships from Institut Curie, Seneca Foundation (20941/PD/18), and ANRS (ECTZ171453). A.N.S. was supported in part by the European Union’s Horizon 2020 research and innovation program (789645 Marie Sklodowska-Curie grant). Y.-H.C. is supported by an A∗STAR International Fellowship. J. Bohlen is an EMBO postdoctoral fellow. We thank the NIH Tetramer Core Facility (NTCF) for providing the 5-OP-RU-loaded MR1 tetramer, which was developed jointly with Dr. James McCluskey, Dr. Jamie Rossjohn, and Dr. David Fairlie., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CE17-0005,GENMSMD,Dissection génétique de la Susceptibilité Mendélienne aux infections mycobactériennes chez l'homme(2016), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), ANR-19-CE15-0012,SUNLIVE,Variabilité structurale et fonctionnelle des lipides complexes chez les mycobactéries : de l'assemblage de la paroi à la physiopathologie et virulence(2019), ANR-22-CE92-0008,MAFMACRO,Genetic predisposition and the role of myeloid cells in the susceptibility to mycobacterial infection(2022), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), and TÜREL, ÖZDEN
- Subjects
inborn errors of immunity ,Temel Bilimler ,[SDV]Life Sciences [q-bio] ,interferon-stimulated gene ,Life Sciences ,Molecular Biology and Genetics ,Genel Biyokimya, Genetik ve Moleküler Biyoloji ,IRF1 ,General Biochemistry, Genetics and Molecular Biology ,Mycobacterium ,macrophages ,interferon-γ ,Yaşam Bilimleri ,viruses ,Cytogenetic ,Natural Sciences ,Moleküler Biyoloji ve Genetik ,Sitogenetik - Abstract
Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/β-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/β-dependent antiviral immunity.
- Published
- 2023
19. Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination
- Author
-
Aurélien Sokal, Paul Bastard, Pascal Chappert, Giovanna Barba-Spaeth, Slim Fourati, Alexis Vanderberghe, Pauline Lagouge-Roussey, Isabelle Meyts, Adrian Gervais, Magali Bouvier-Alias, Imane Azzaoui, Ignacio Fernández, Andréa de la Selle, Qian Zhang, Lucy Bizien, Isabelle Pellier, Agnès Linglart, Anya Rothenbuhler, Estelle Marcoux, Raphael Anxionnat, Nathalie Cheikh, Juliane Léger, Blanca Amador-Borrero, Fanny Fouyssac, Vanessa Menut, Jean-Christophe Goffard, Caroline Storey, Caroline Demily, Coralie Mallebranche, Jesus Troya, Aurora Pujol, Marie Zins, Pierre Tiberghien, Paul E. Gray, Peter McNaughton, Anna Sullivan, Jane Peake, Romain Levy, Laetitia Languille, Carlos Rodiguez-Gallego, Bertrand Boisson, Sébastien Gallien, Bénédicte Neven, Marc Michel, Bertrand Godeau, Laurent Abel, Felix A. Rey, Jean-Claude Weill, Claude-Agnès Reynaud, Stuart G. Tangye, Jean-Laurent Casanova, Matthieu Mahévas, 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), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University [New York], 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), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Henri Mondor [Créteil], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Saclay, Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), Service de pédiatrie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), AP-HP. Nord - Université Paris Cité, Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Hôpital Mère-Enfant [Hôpital Hôtel Dieu, Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Université libre de Bruxelles (ULB), Hôpital Robert Debré, Centre Hospitalier le Vinatier [Bron], Hospital Universitario Infanta Leonor [Madrid], Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Sydney Children's hospital, University of New South Wales [Sydney] (UNSW), Children’s Health Queensland [Brisbane] (CHQ), CHU Necker - Enfants Malades [AP-HP], Universidad Fernando Pessoa Canarias [Las Palmas de Gran Canaria, Spain], Garvan Institute of medical research, Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), Funder(s): Agence Nationale de la Recherche Award Id(s): ANR-21-RHUS-0008, ANR-10-IAHU-01, ANR-10-LABX-62-IBEID , ANR-20-CE93-003Funder(s): Fondation pour la Recherche MédicaleAward Id(s): MEMO-COV-2-FRMFunder(s): Institut PasteurFunder(s): Agence Nationale de Recherches sur le Sida et les Hépatites ViralesFunder(s): Howard Hughes Medical InstituteFunder(s): Rockefeller UniversityFunder(s): St. Giles FoundationFunder(s): National Institutes of Health Award Id(s): R01AI088364, R01AI163029, UL1TR001866Funder(s): National Center for Advancing Translational SciencesFunder(s): Fisher Center for Alzheimer’s Research FoundationFunder(s): Meyer FoundationFunder(s): JPB FoundationFunder(s): French Foundation for Medical Research Award Id(s): EQU201903007798, EA20170638020Funder(s): European Union’s Horizon 2020 Award Id(s): 824110Funder(s): Square FoundationFunder(s): Fondation du SouffleFunder(s): French Ministry of Higher Education, Research, and Innovation Award Id(s): MESRI-COVID-19Funder(s): Institut National de la Santé et de la Recherche MédicaleFunder(s): Fondation Bettencourt SchuellerFunder(s): CSL BehringFunder(s): KU Leuven Award Id(s): C16/18/007Funder(s): http://dx.doi.org/10.13039/501100003130 Award Id(s): G0C8517N, G0B5120N, G0E8420NFunder(s): Jeffrey Modell FoundationFunder(s): National Health and Medical Research Council Award Id(s): 1176665Funder(s): Allergy and Immunology Foundation of AustraliaFunder(s): John Brown Cook FoundationFunder(s): Fondation Princesse GraceFunder(s): Comité ad-hoc de pilotage national des essais thérapeutiques et autres recherchesFunder(s): Assistance Publique—Hôpitaux de Paris Award Id(s): MEMO-COV-2Funder(s): Société Nationale de Médecine InterneFunder(s): ANRS Nord-Sud Award Id(s): ANRS-COV05Funder(s): ANR-RHU Award Id(s): ANR-21-RHUS-08 (COVIFERON)Funder(s): HORIZON-HLTH-2021-DISEASE-04 Award Id(s): 01057100Funder(s): Grandir - Fonds de solidarité pour l’enfanceFunder(s): SCOR Corporate Foundation for ScienceFunder(s): REACTing-INSERMFunder(s): University of Paris CitéFunder(s): Imagine InstituteFunder(s): VIB GC PIDFunder(s): European Research Council Award Id(s): ERC-StG MORE2ADA2, ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), European Project: 948959,ERC-2020-STG,MORE2ADA2(2021), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and CHU Henri Mondor
- Subjects
EXPRESSION ,COVID-19 Vaccines ,Immunology ,VECTOR ,Research & Experimental Medicine ,Antibodies, Viral ,DISEASE ,Immunology and Allergy ,Humans ,PSEUDOURIDINE ,Autoantibodies ,B-Lymphocytes ,Science & Technology ,SARS-CoV-2 ,Vaccination ,COVID-19 ,Antibodies, Neutralizing ,Medicine, Research & Experimental ,Toll-Like Receptor 7 ,ANTIBODIES ,Spike Glycoprotein, Coronavirus ,Interferon Type I ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,mRNA Vaccines ,[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology ,Life Sciences & Biomedicine - Abstract
Inborn and acquired deficits of type I interferon (IFN) immunity predispose to life-threatening COVID-19 pneumonia. We longitudinally profiled the B cell response to mRNA vaccination in SARS-CoV-2 naive patients with inherited TLR7, IRF7, or IFNAR1 deficiency, as well as young patients with autoantibodies neutralizing type I IFNs due to autoimmune polyendocrine syndrome type-1 (APS-1) and older individuals with age-associated autoantibodies to type I IFNs. The receptor-binding domain spike protein (RBD)-specific memory B cell response in all patients was quantitatively and qualitatively similar to healthy donors. Sustained germinal center responses led to accumulation of somatic hypermutations in immunoglobulin heavy chain genes. The amplitude and duration of, and viral neutralization by, RBD-specific IgG serological response were also largely unaffected by TLR7, IRF7, or IFNAR1 deficiencies up to 7 mo after vaccination in all patients. These results suggest that induction of type I IFN is not required for efficient generation of a humoral response against SARS-CoV-2 by mRNA vaccines. ispartof: JOURNAL OF EXPERIMENTAL MEDICINE vol:220 issue:1 ispartof: location:United States status: published
- Published
- 2023
20. [Review] Deep Eutectic Solvents Comprising Organic Acids and Their Application in (Bio)Medicine
- Author
-
Tomasz Swebocki, Alexandre Barras, Amar Abderrahmani, Kamel Haddadi, Rabah Boukherroub, University of Lille, Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 [IEMN], NanoBioInterfaces - IEMN [NBI - IEMN], Circuits Systèmes Applications des Micro-ondes - IEMN [CSAM - IEMN ], Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), NanoBioInterfaces - IEMN (NBI - IEMN), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Circuits Systèmes Applications des Micro-ondes - IEMN (CSAM - IEMN ), Funding: The doctorate of TS is financed by the French Ministry of Higher Education, Research,and Innovation (MESRI). The CNRS, the University of Lille and the Hauts-de-France region areacknowledged for financial support., Acknowledgments: Figure 4 and the graphical abstract have been created using Biorender® softwareassets. The CNRS, the University of Lille, the Hauts-de-France region, and the Agence Nationale dela Recherche (project: MSN-2hv) are acknowledged for financial support., and ANR-19-CE09-0034,MSN-2hv,Matériaux théranostiques associant les fonctionnalités d'imagerie 2 photons et de thérapie photodynamique pour le ciblage de bactéries et le contrôle des infections lors de la cicatrisation(2019)
- Subjects
Organic Chemistry ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,General Medicine ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,organic acids ,drug delivery ,enhancers ,antimicrobial treatment ,Physical and Theoretical Chemistry ,Molecular Biology ,deep eutectic solvents ,Spectroscopy - Abstract
International audience; Over the last years, we observed a significant increase in the number of published studies that focus on the synthesis and characterization of deep eutectic solvents (DESs). These materials are of particular interest mainly due to their physical and chemical stability, low vapor pressure, ease of synthesis, and the possibility of tailoring their properties through dilution or change of the ratio of parent substances (PS). DESs, considered as one of the greenest families of solvents, are used in many fields, such as organic synthesis, (bio)catalysis, electrochemistry, and (bio)medicine. DESs applications have already been reported in various review articles. However, these reports mainly described these components’ basics and general properties without focusing on the particular, PS-wise, group of DESs. Many DESs investigated for potential (bio)medical applications comprise organic acids. However, due to the different aims of the reported studies, many of these substances have not yet been investigated thoroughly, which makes it challenging for the field to move forward. Herein, we propose distinguishing DESs comprising organic acids (OA-DESs) as a specific group derived from natural deep eutectic solvents (NADESs). This review aims to highlight and compare the applications of OA-DESs as antimicrobial agents and drug delivery enhancers—two essential fields in (bio)medical studies where DESs have already been implemented and proven their potential. From the survey of the literature data, it is evident that OA-DESs represent an excellent type of DESs for specific biomedical applications, owing to their negligible cytotoxicity, fulfilling the rules of green chemistry and being generally effective as drug delivery enhancers and antimicrobial agents. The main focus is on the most intriguing examples and (where possible) application-based comparison of particular groups of OA-DESs. This should highlight the importance of OA-DESs and give valuable clues on the direction the field can take.
- Published
- 2023
21. Behavioural syndrome between boldness and aggressiveness and link with reproductive success in a wild bird population
- Author
-
Thibault Tamin, Jennifer Morinay, Marion Germain, Charlotte Récapet, Blandine Doligez, 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), Department of Ecology and Genetics [Uppsala] (EBC), Uppsala University, Département d'écologie et évolution [Lausanne] (DEE), Université de Lausanne = University of Lausanne (UNIL), Ecologie Comportementale et Biologie des Populations de Poissons (ECOBIOP), Université de Pau et des Pays de l'Adour (UPPA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French Ministry of Higher Education and Research, CNRS, Region Rhone-Alpes, and Zoological Institute of Uppsala University
- Subjects
behavioural test ,fledging success ,neophobia ,recruitment ,Ficedula albicollis ,personality trait ,Animal Science and Zoology ,among- and within-individual correlation ,collared flycatcher ,heritability ,repeatability ,[SDE.BE]Environmental Sciences/Biodiversity and Ecology ,Ecology, Evolution, Behavior and Systematics - Abstract
International audience; Boldness, defined as the behavioural response of individuals when facing a risky situation, is a majorpersonality trait and often phenotypically correlates with other behavioural traits, in particular aggressiveness,exploration behaviour and neophobia. Yet, whether such links result from among-individualcorrelations, i.e. form behavioural syndromes sensu stricto, is often ignored and whether such syndromesmay yield individual fitness benefits, and thus be selected for, remains poorly explored. Wemeasured boldness as the nest defence behaviour against a dummy nest predator in a natural populationof a small passerine bird, the collared flycatcher, Ficedula albicollis, and investigated the existence of abehavioural syndrome between boldness and two other behavioural traits, aggressiveness (measured asthe agonistic response to competitors) and neophobia (measured as the behavioural response to a novelobject in a known environment). Then we assessed the links between this potential syndrome andreproductive success, measured as fledging and recruitment success. Boldness score differed between thesexes and depended on whether the partner was present during the test. Nevertheless, it was repeatable,showing that boldness can be considered as a personality trait in our population. We found a positiveamong-individual correlation between boldness and aggressiveness, showing the existence of a behaviouralsyndrome between both personality traits. This syndrome was related to reproductive success: thenumber of fledged young (but not recruitment probability) increased with one integrative value of theboldnesseaggressiveness syndrome. Conversely, boldness score was not correlated with neophobia. Ourresults thus clearly reveal a behavioural syndrome between boldness and aggressiveness with possibleconsequences for reproductive success in the study population, and therefore raise the question of theevolutionary implications of such a behavioural syndrome
- Published
- 2023
22. Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children
- Author
-
Lee, Danyel, Le Pen, Jérémie, Yatim, Ahmad, Dong, Beihua, Aquino, Yann, Ogishi, Masato, Pescarmona, Rémi, Talouarn, Estelle, Rinchai, Darawan, Zhang, Peng, Perret, Magali, Liu, Zhiyong, Jordan, Iolanda, Elmas Bozdemir, Sefika, Bayhan, Gulsum Iclal, Beaufils, Camille, Bizien, Lucy, Bisiaux, Aurelie, Lei, Weite, Hasan, Milena, Chen, Jie, Gaughan, Christina, Asthana, Abhishek, Libri, Valentina, Luna, Joseph, Jaffré, Fabrice, Hoffmann, H.-Heinrich, Michailidis, Eleftherios, Moreews, Marion, Seeleuthner, Yoann, Bilguvar, Kaya, Mane, Shrikant, Flores, Carlos, Zhang, Yu, Arias, Andrés, Bailey, Rasheed, Schlüter, Agatha, Milisavljevic, Baptiste, Bigio, Benedetta, Le Voyer, Tom, Materna, Marie, Gervais, Adrian, Moncada-Velez, Marcela, Pala, Francesca, Lazarov, Tomi, Levy, Romain, Neehus, Anna-Lena, Rosain, Jérémie, Peel, Jessica, Chan, Yi-Hao, Morin, Marie-Paule, Pino-Ramirez, Rosa Maria, Belkaya, Serkan, Lorenzo, Lazaro, Anton, Jordi, Delafontaine, Selket, Toubiana, Julie, Bajolle, Fanny, Fumadó, Victoria, Dediego, Marta, Fidouh, Nadhira, Rozenberg, Flore, Pérez-Tur, Jordi, Chen, Shuibing, Evans, Todd, Geissmann, Frédéric, Lebon, Pierre, Weiss, Susan, Bonnet, Damien, Duval, Xavier, Pan-Hammarström, Qiang, Planas, Anna, Meyts, Isabelle, Haerynck, Filomeen, Pujol, Aurora, Sancho-Shimizu, Vanessa, Dalgard, Clifford, Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Boisson, Bertrand, Maniatis, Tom, Zhang, Qian, Bastard, Paul, Notarangelo, Luigi, Béziat, Vivien, Perez de Diego, Rebeca, Rodriguez-Gallego, Carlos, Su, Helen, Lifton, Richard, Jouanguy, Emmanuelle, Cobat, Aurélie, Alsina, Laia, Keles, Sevgi, Haddad, Elie, Abel, Laurent, Belot, Alexandre, Quintana-Murci, Lluis, Rice, Charles, Silverman, Robert, Zhang, Shen-Ying, Casanova, Jean-Laurent, Alavoine, Loubna, Behillil, Sylvie, Burdet, Charles, Charpentier, Charlotte, Dechanet, Aline, Descamps, Diane, Ecobichon, Jean-Luc, Enouf, Vincent, Frezouls, Wahiba, Houhou, Nadhira, Kafif, Ouifiya, Lehacaut, Jonathan, Letrou, Sophie, Lina, Bruno, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Piquard, Valentine, Quintin, Caroline, Thy, Michael, Tubiana, Sarah, van der Werf, Sylvie, Vignali, Valérie, Visseaux, Benoit, Yazdanpanah, Yazdan, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Deplanque, Dominique, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Laine, Fabrice, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Malvy, Denis, Nguyen, Duc, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Chirouze, Catherine, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Lefèvre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Christelle, Kouakam, Nicolas, Leturque, Roufai, Layidé, Amat, Karine, Couffin-Cadiergues, Sandrine, Espérou, Hélène, Hendou, Samia, Abolhassani, Hassan, Aguilera-Albesa, Sergio, Aiuti, Alessandro, Akcan, Ozge Metin, Akcay, Nihal, Alkan, Gulsum, Alkhater, Suzan, Allende, Luis Miguel, Alper, Yosunkaya, Amenzoui, Naima, Anderson, Mark, Arkin, Lisa, Aubart, Melodie, Avramenko, Iryna, Aydemir, Şehnaz, Gayretli Aydin, Zeynep Gökçe, Aytekin, Caner, Aytekin, Gökhan, Erol Aytekin, Selma, Bando, Silvia Yumi, Beland, Kathie, Biggs, Catherine, Bilbao Aburto, Agurtzane, Blanchard-Rohner, Geraldine, Blázquez-Gamero, Daniel, Bloomfield, Marketa, Bogunovic, Dusan, Bondarenko, Anastasia, Borghesi, Alessandro, Bousfiha, Amed Aziz, Boyarchuk, Oksana, Brodin, Petter, Bryceson, Yenan, Bucciol, Giorgia, Calcaterra, Valeria, Casari, Giorgio, Cavalcanti, Andre, Celik, Jale Bengi, Chrousos, George, Colobran, Roger, Condino-Neto, Antonio, Conti, Francesca, Cooper, Megan, Coskuner, Taner, Cyrus, Cyril, D’auria, Enza, Drolet, Beth, Bursal Duramaz, Burcu, El Zein, Loubna, Elnagdy, Marwa, Emiroglu, Melike, Erdeniz, Emine Hafize, Fabi, Marianna, Baris Feldman, Hagit, Fellay, Jacques, Fencl, Filip, Filippatos, Filippos, Freiss, Julie, Fremuth, Jiri, Gagro, Alenka, Garcia-Solis, Blanca, Vergine, Gianluca, González-Montelongo, Rafaela, Gul, Yahya, Gülhan, Belgin, Gultekin, Sara Sebnem Kilic, Gut, Marta, Halwani, Rabih, Hammarström, Lennart, Hatipoğlu, Nevin, Heath, James, Henrickson, Sarah, Hernandez-Brito, Elisa, Hoffman, Ilse, Hoste, Levi, Hsieh, Elena, Íñigo-Campos, Antonio, Itan, Yuval, Jabandziev, Petr, Kandemir, Bahar, Kanık-Yüksek, Saliha, Kapakli, Hasan, Karbuz, Adem, Kasapcopur, Ozgur, Kechiche, Robin, Kendir Demirkol, Yasemin, Kilic, Omer, Hansen, Stella Kim, Klocperk, Adam, Lau, Yu-Lung, Lebl, Jan, Lorenzo-Salazar, José, Lucas, Carrie, Maglorius, Majistor, Marque, Laura, Novoa Medina, Yeray, Montesdeoca Melián, Abián, Mentis, Alexios-Fotios, Pato, Michele, Michos, Athanasios, Milner, Joshua, Mogensen, Trine, Muñoz-Barrera, Adrián, Nepesov, Serdar, Farela Neves, João, Ng, Ashley, Ng, Lisa, Novelli, Antonio, Novelli, Giuseppe, Oz, Fatma Nur, Ocejo-Viñals, J. Gonzalo, Okada, Satoshi, Orbak, Zerrin, Kilic, Ahmet Osman, Ouair, Hind, Öz, Şadiye Kübra Tüter, Özçelik, Tayfun, Özkan, Esra Akyüz, Parlakay, Aslınur Özkaya, Pato, Carlos, Paz-Artal, Estela, Pelham, Simon, Pellier, Isabelle, Philippot, Quentin, Planas-Serra, Laura, Plassart, Samira, Pokorna, Petra, Polat, Meltem, Poli, Cecilia, Prando, Carolina, Renia, Laurent, Rivière, Jacques, Rodríguez-Palmero, Agustí, Roussel, Lucie, Rubio-Rodriguez, Luis, Salifu, Moro, Sasek, Lumir, Sasia, Laura, Scherbina, Anna, Schmitt, Erica, Sediva, Anna, Sevketoglu, Esra, Slaba, Katerina, Slaby, Ondrej, Sobh, Ali, Solé-Violán, Jordi, Soler-Palacin, Pere, de Somer, Lien, Sözeri, Betül, Spaan, András, Stepanovskiy, Yuriy, Tangye, Stuart, Tanir, Gonul, Tatsi, Elizabeth Barbara, Thorball, Christian, Hancerli Torun, Selda, Turvey, Stuart, Uddin, Mohammed, Uyar, Emel, Valencia-Ramos, Juan, van den Rym, Ana Maria, Vatansev, Hulya, Castillo de Vera, Martín, Vermeulen, François, Vinh, Donald, Volokha, Alla, von Bernuth, Horst, Wouters, Carine, Yahşi, Aysun, Yarar, Volkan, Yesilbas, Osman, Yıldız, Mehmet, Zatz, Mayana, Zawadzki, Pawel, Zuccotti, Gianvincenzo, Rockefeller University [New York], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Génomique évolutive, modélisation et santé (GEMS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sidra Medicine [Doha, Qatar], BIOASTER Technology Research Institute, Lyon, France, St. Giles Laboratory of Human Genetics of Infectious Diseases, Department of Paediatrics and Intensive Care, Hospital Universitari Sant Joan de Deu, Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique Evolutive Humaine - Human Evolutionary Genetics, Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Shanghai Jiaotong University, Sheffield Hallam University, Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre d'Investigation Clinique de La Réunion - INSERM (CIC 1410), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R21AI160576), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High-Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JBP Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANR GenMISC (ANR-21-COVR-039), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the ANR-RHU program (ANR-21-RHUS-08), the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the ANR-RHU Program ANR-21-RHUS-08 (COVIFERON), the Square Foundation, Grandir – Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), and Paris Cité University. We acknowledge support from the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH under award R01AI104887 to R.H.S. and S.R.W. The Laboratory of Human Evolutionary Genetics (Institut Pasteur) is supported by the Institut Pasteur, the Collège de France, the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID) and 'Milieu Intérieur' (ANR-10-LABX-69-01), the Fondation de France (no. 00106080), the FRM (Equipe FRM DEQ20180339214 team), and the ANR COVID-19-POPCELL (ANR-21-CO14-0003-01). A.Puj. is supported by ACCI20-759 CIBERER, EasiGenomics H2020 Marató TV3 COVID 2021-31-33, the HORIZON-HLTH-2021-ID: 101057100 (UNDINE), the Horizon 2020 program under grant no. 824110 (EasiGenomics grant no. COVID-19/PID12342), and the CERCA Program/Generalitat de Catalunya. The Canarian Health System sequencing hub was funded by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1, AEI/FEDER, UE), Fundación MAPFRE Guanarteme (OA21/131), and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). The CoV-Contact Cohort was funded by the French Ministry of Health and the European Commission (RECOVER project). Our studies are also funded by the Ministry of Health of the Czech Republic Conceptual Development of Research Organization (FNBr, 65269705) and ANID COVID0999 funding in Chile. G. Novelli and A. Novelli are supported by Regione Lazio (Research Group Projects 2020) No. A0375-2020-36663, GecoBiomark. A.M.P., M.L.D., and J.P.-T. are supported by the Inmungen-CoV2 project of CSIC. This work was supported in part by the Intramural Research Program of the NIAID, NIH. The research work of A.M.P, M.L.D., and J.P.-T. was funded by the European Commission –NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global). I.M. is a senior clinical investigator at FWO Vlaanderen supported by a VIB GC PID grant, by FWO grants G0B5120N (DADA2) and G0E8420N, and by the Jeffrey Modell Foundation. I.M. holds an ERC-StG MORE2ADA2 grant and is also supported by ERN-RITA. A.Y. is supported by fellowships from the European Academy of Dermatology and Venereology and the Swiss National Science Foundation and by an Early Career Award from the Thrasher Research Fund. Y.-H.C. is supported by an A*STAR International Fellowship (AIF). M.O. was supported by the David Rockefeller Graduate Program, the New York Hideyo Noguchi Memorial Society (HNMS), the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the National Cancer Institute (NCI) F99 Award (F99CA274708). A.A.A. was supported by Ministerio de Ciencia Tecnología e Innovación MINCIENCIAS, Colombia (111584467551/CT 415-2020). D.L. is supported by a fellowship from the FRM for medical residents and fellows. E.H. received funding from the Bank of Montreal Chair of Pediatric Immunology, Foundation of CHU Sainte-Justine, CIHR grants PCC-466901 and MM1-181123, and a Canadian Pediatric Society IMPACT study. Q.P.-H. received funding from the European Union’s Horizon 2020 research and innovation program (ATAC, 101003650), the Swedish Research Council, and the Knut and Alice Wallenberg Foundation. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, R01AI091707-10S1, and R01AI161444, a George Mason University Fast Grant, the G. Harold and Leila Y. Mathers Charitable Foundation, the Meyer Foundation, and the Bawd Foundation. R.P.L. is on the board of directors of both Roche and the Roche subsidiary Genentech. J.L.P. was supported by a Francois Wallace Monahan Postdoctoral Fellowship at the Rockefeller University and by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018)., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-21-CO14-0003,COVID-19-POPCELL,Facteurs génétiques et infectieux à l'origine de la variabilité populationnelle de la réponse immunitaire à l'infection par le SARS-CoV-2(2021), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), European Project: 101057100,UNDINE, Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundación Mapfre, Cabildo de Tenerife, Fundació La Marató de TV3, Centro de Investigación Biomédica en Red Enfermedades Raras (España), Consejo Superior de Investigaciones Científicas (España), European Commission, and Pérez-Tur, Jordi
- Subjects
Multidisciplinary ,Settore MED/03 ,[SDV]Life Sciences [q-bio] ,Medicine and Health Sciences ,CoV-Contact Cohort§ - Abstract
62 páginas, 5 figuras, 2 tablas, Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R21AI160576), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High-Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JBP Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10- LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANR GenMISC (ANR-21-COVR-039), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the ANR-RHU program (ANR-21-RHUS-08), the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the ANR-RHU Program ANR-21- RHUS-08 (COVIFERON), the Square Foundation, Grandir – Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), and Paris Cité University. We acknowledge support from the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH under award R01AI104887 to R.H.S. and S.R.W. The Laboratory of Human Evolutionary Genetics (Institut Pasteur) is supported by the Institut Pasteur, the Collège de France, the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence “Integrative Biology of Emerging Infectious Diseases” (ANR-10-LABX-62-IBEID) and “Milieu Intérieur” (ANR-10-LABX-69-01), the Fondation de France (no. 00106080), the FRM (Equipe FRM DEQ20180339214 team), and the ANR COVID-19-POPCELL (ANR-21-CO14-0003-01). A.Puj. is supported by ACCI20-759 CIBERER, EasiGenomics H2020 Marató TV3 COVID 2021-31-33, the HORIZON-HLTH-2021-ID: 101057100 (UNDINE), the Horizon 2020 program under grant no. 824110 (EasiGenomics grant no. COVID-19/PID12342), and the CERCA Program/Generalitat de Catalunya. The Canarian Health System sequencing hub was funded by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, UE), Fundación MAPFRE Guanarteme (OA21/131), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). The CoV-Contact Cohort was funded by the French Ministry of Health and the European Commission (RECOVER project). Our studies are also funded by the Ministry of Health of the Czech Republic Conceptual Development of Research Organization (FNBr, 65269705) and ANID COVID0999 funding in Chile. G. Novelli and A. Novelli are supported by Regione Lazio (Research Group Projects 2020) No. A0375-2020-36663, GecoBiomark. A.M.P., M.L.D., and J.P.-T. are supported by the Inmungen-CoV2 project of CSIC. This work was supported in part by the Intramural Research Program of the NIAID, NIH. The research work of A.M..P, M.L.D., and J.P.-T. was funded by the European Commission –NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global). I.M. is a senior clinical investigator at FWO Vlaanderen supported by a VIB GC PID grant, by FWO grants G0B5120N (DADA2) and G0E8420N, and by the Jeffrey Modell Foundation. I.M. holds an ERC-StG MORE2ADA2 grant and is also supported by ERN-RITA. A.Y. is supported by fellowships from the European Academy of Dermatology and Venereology and the Swiss National Science Foundation and by an Early Career Award from the Thrasher Research Fund. Y.-H.C. is supported by an A*STAR International Fellowship (AIF). M.O. was supported by the David Rockefeller Graduate Program, the New York Hideyo Noguchi Memorial Society (HNMS), the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the National Cancer Institute (NCI) F99 Award (F99CA274708). A.A.A. was supported by Ministerio de Ciencia Tecnología e Innovación MINCIENCIAS, Colombia (111584467551/CT 415-2020). D.L. is supported by a fellowship from the FRM for medical residents and fellows. E.H. received funding from the Bank of Montreal Chair of Pediatric Immunology, Foundation of CHU Sainte-Justine, CIHR grants PCC-466901 and MM1-181123, and a Canadian Pediatric Society IMPACT study. Q.P.-H. received funding from the European Union’s Horizon 2020 research and innovation program (ATAC, 101003650), the Swedish Research Council, and the Knut and Alice Wallenberg Foundation. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, R01AI091707-10S1, and R01AI161444; a George Mason University Fast Grant; the G. Harold and Leila Y. Mathers Charitable Foundation; the Meyer Foundation; and the Bawd Foundation. R.P.L. is on the board of directors of both Roche and the Roche subsidiary Genentech. J.L.P. was supported by a Francois Wallace Monahan Postdoctoral Fellowship at the Rockefeller University and by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018).
- Published
- 2023
23. CSF-contacting neurons respond to Streptococcus pneumoniae and promote host survival during central nervous system infection
- Author
-
Andrew E. Prendergast, Kin Ki Jim, Hugo Marnas, Laura Desban, Feng B. Quan, Lydia Djenoune, Valerio Laghi, Agnès Hocquemiller, Elias T. Lunsford, Julian Roussel, Ludovic Keiser, Francois-Xavier Lejeune, Mahalakshmi Dhanasekar, Pierre-Luc Bardet, Jean-Pierre Levraud, Diederik van de Beek, Christina M.J.E. Vandenbroucke-Grauls, Claire Wyart, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Amsterdam [Amsterdam] (UvA), Vrije Universiteit Amsterdam [Amsterdam] (VU), Amsterdam institute for Infection and Immunity [Amsterdam, The Netherlands] (A3I), Macrophages et Développement de l’Immunité, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ecole Polytechnique Fédérale de Lausanne (EPFL), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Fondation Schlumberger pour l’Education et la Recherche (FSER/2017), the Fondation pour la Recherche Médicale (FRM no. Equation 202003010612), the ERC Starting Grant 'Optoloco' no. 311673, ERC PoC 'ZebraZoom' no. 825273, and ERC Consolidator Grant 'Exploratome' no. 101002870 (to C.W.). We acknowledge support from 'MeninGene' no. 281156 and the HFSP Program grant nos. RGP0063/2014 and RGP0063/2017 and grants from the Agence Nationale de la Recherche (ANR) ASCENTS no. ANR-21-CE13-0008, MOTOMYO no. ANR-21-CE14-0042, and ANR LOCOCONNECT no. ANR-22-CE37-0023 et la Fondation Bettencourt-Schueller don 0031. D.v.d.B. was supported by a ZonMw VICI grant no. 391819627. A.E.P. was supported by an EMBO long-term fellowship (ALTF-549-2013) and a Research in Paris grant from the Marie de Paris. L. Desban was supported by the French Ministry of Higher Education and Research doctoral fellowship. M.D. was supported by a PhD fellowship from the Sorbonne Université Ecole Doctorale ED3C., ANR-21-CE13-0008,ASCENTS,Étude d'une asymétrie structurelle nouvellement identifiée du centriole des vertébrés et de son impact sur le développement et la santé(2021), ANR-21-CE14-0042,MOTOMYO,Appariement entre sous types de motoneurones et sous types de myofibres: du développement à la pathologie(2021), ANR-22-CE37-0023,LOCONNECT,Transmission d'information causale lors de la locomotion(2022), European Project: 311673,EC:FP7:ERC,ERC-2012-StG_20111109,OPTOLOCO(2013), Medical Microbiology and Infection Prevention, AII - Infectious diseases, AII - Inflammatory diseases, Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, ANS - Neuroinfection & -inflammation, and Neurology
- Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,in-situ hybridization ,interoception ,substance inducing transformation ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,General Biochemistry, Genetics and Molecular Biology ,cerebrospinal fluid ,volatile metabolites ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,central nervous system infection ,innate immunity ,cytolysins ,solitary chemosensory cells ,pneumococcal types ,chemical nature ,zebrafish ,gene-expression ,pathogen detection ,cerebrospinal-fluid ,cytokines ,sensory neurons ,host defense ,peptides ,taste receptors ,neurosecretion ,General Agricultural and Biological Sciences ,bacterial meningitis ,bitter compounds - Abstract
International audience; The pathogenic bacterium Streptococcus pneumoniae (S. pneumoniae) can invade the cerebrospinal fluid (CSF) and cause meningitis with devastating consequences. Whether and how sensory cells in the central nervous system (CNS) become activated during bacterial infection, as recently reported for the peripheral nervous system, is not known. We find that CSF infection by S. pneumoniae in larval zebrafish leads to changes in posture and behavior that are reminiscent of pneumococcal meningitis, including dorsal arching and epileptic-like seizures. We show that during infection, invasion of the CSF by S. pneumoniae massively activates in vivo sensory neurons contacting the CSF, referred to as “CSF-cNs” and previously shown to detect spinal curvature and to control posture, locomotion, and spine morphogenesis. We find that CSF-cNs express orphan bitter taste receptors and respond in vitro to bacterial supernatant and metabolites via massive calcium transients, similar to the ones observed in vivo during infection. Upon infection, CSF-cNs also upregulate the expression of numerous cytokines and complement components involved in innate immunity. Accordingly, we demonstrate, using cell-specific ablation and blockade of neurotransmission, that CSF-cN neurosecretion enhances survival of the host during S. pneumoniae infection. Finally, we show that CSF-cNs respond to various pathogenic bacteria causing meningitis in humans, as well as to the supernatant of cells infected by a neurotropic virus. Altogether, our work uncovers that central sensory neurons in the spinal cord, previously involved in postural control and morphogenesis, contribute as well to host survival by responding to the invasion of the CSF by pathogenic bacteria during meningitis.
- Published
- 2023
24. Defective activation and regulation of type I interferon immunity is associated with increasing COVID-19 severity
- Author
-
Nikaïa Smith, Céline Possémé, Vincent Bondet, Jamie Sugrue, Liam Townsend, Bruno Charbit, Vincent Rouilly, Violaine Saint-André, Tom Dott, Andre Rodriguez Pozo, Nader Yatim, Olivier Schwartz, Minerva Cervantes-Gonzalez, Jade Ghosn, Paul Bastard, Jean Laurent Casanova, Tali-Anne Szwebel, Benjamin Terrier, Niall Conlon, Cliona O’Farrelly, Clíona Ní Cheallaigh, Nollaig M. Bourke, Darragh Duffy, Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Trinity College Dublin, Saint James Hospital (SJH), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Datactix, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, CHU Necker - Enfants Malades [AP-HP], Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University [New York], Howard Hughes Medical Institute (HHMI), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This study was supported by the 'URGENCE COVID-19' fundraising campaign of the Institut Pasteur (CoVarImm and Steroid Response), from the Agence Nationale de la Recherche (ANR-flash COVID-19), by the Laboratoire d’Excellence ‘Milieu Intérieur’ (grant no. ANR-10-LABX-69-01) (D.D.), the Fonds IMMUNOV for Innovation in Immunopathology (B.T.), and Science Foundation Ireland (C.O.F., C.N.C., and N.B.). We thank the STTAR-Bioresource of TCD-SJH-TUH COVID-19 bioresource which supported the collection of patient samples. N.S. is a recipient of the Pasteur–Roux–Cantarini Fellowship. C.O.F., N.C., and C.N.C. are part-funded by a Science Foundation Ireland (SFI) grant, Grant Code 20/SPP/3685. L.T. is supported by the Irish Clinical Academic Training (ICAT) Program, supported by the Wellcome Trust and the Health Research Board (Grant Number 203930/B/16/Z), the Health Service Executive, National Doctors Training and Planning and the Health and Social Care, Research and Development Division, Northern Ireland. N.B. is funded under the Science Foundation Ireland Phase 2 COVID-19 Rapid Response Call (20/COV/8487) and the Health Research Board COVID-19 Rapid Response Call (COV19e2020e053). The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), ANR AABIFNCOV (ANR-20-CO11-0001) and ANR GenMISC (ANR-21-COVR-0039) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement No. 824110 (EASI-genomics), the Square Foundation, Grandir—Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, The French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM and the University of Paris (J.L.C.). P.B. was supported by the MD–Ph.D. program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller)., We thank the UTechS CB of the Center for Translational Research, Institut Pasteur for supporting Luminex and Nanostring analysis. We thank Quanterix for the provision of IFNα multi-subtype prototype assays. We acknowledge all healthcare workers involved in the diagnosis and treatment of patients in Hopital Cochin, Hopital Bichat, and St James’s Hospital Dublin., ANR-20-COVI-0053,CoVarImm,Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence(2020), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), and European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019)
- Subjects
Proteomics ,Multidisciplinary ,SARS-CoV-2 ,[SDV]Life Sciences [q-bio] ,Interferon Type I ,General Physics and Astronomy ,Humans ,COVID-19 ,Interferon-alpha ,General Chemistry ,Antiviral Agents ,General Biochemistry, Genetics and Molecular Biology ,Autoantibodies - Abstract
Host immunity to infection with SARS-CoV-2 is highly variable, dictating diverse clinical outcomes ranging from asymptomatic to severe disease and death. We previously reported reduced type I interferon in severe COVID-19 patients preceded clinical worsening. Further studies identified genetic mutations in loci of the TLR3- or TLR7-dependent interferon-I pathways, or neutralizing interferon-I autoantibodies as risk factors for development of COVID-19 pneumonia. Here we show in patient cohorts with different severities of COVID-19, that baseline plasma interferon α measures differ according to the immunoassay used, timing of sampling, the interferon α subtype measured, and the presence of autoantibodies. We also show a consistently reduced induction of interferon-I proteins in hospitalized COVID-19 patients upon immune stimulation, that is not associated with detectable neutralizing autoantibodies against interferon α or interferon ω. Intracellular proteomic analysis shows increased monocyte numbers in hospitalized COVID-19 patients but impaired interferon-I response after stimulation. We confirm this by ex vivo whole blood stimulation with interferon-I which induces transcriptomic responses associated with inflammation in hospitalized COVID-19 patients, that is not seen in controls or non-hospitalized moderate cases. These results may explain the dichotomy of the poor clinical response to interferon-I based treatments in late stage COVID-19, despite the importance of interferon-I in early acute infection and may guide alternative therapeutic strategies.
- Published
- 2022
25. Broadly neutralizing anti-HIV-1 antibodies tether viral particles at the surface of infected cells
- Author
-
Jérémy Dufloo, Cyril Planchais, Stéphane Frémont, Valérie Lorin, Florence Guivel-Benhassine, Karl Stefic, Nicoletta Casartelli, Arnaud Echard, Philippe Roingeard, Hugo Mouquet, Olivier Schwartz, Timothée Bruel, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Plateforme IBISA de Microscopie Electronique [CHRU de Tours] (UNIV Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), O.S. is funded by Institut Pasteur, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01, and the Gilead HIV cure program. J.D. is funded by a Ph.D grant from the French Ministry of Higher Education and Research. H.M. is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), INSERM, ANRS, and Gilead HIV cure program. C.P. was supported by an ANRS fellowship. A.E. and S.F. are funded by Institut Pasteur, CNRS, and ANRS (ANRS-21020 AP2020-2). P.R. is funded by INSERM, Université de Tours and ANRS., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Institut Pasteur, Agence Nationale de la Recherche (France), Ministére de l'Education Nationale de la Recherche et de la Technologie (France), and Université de Tours
- Subjects
MESH: Epitopes ,T-Lymphocytes ,Science ,viruses ,General Physics and Astronomy ,HIV Infections ,MESH: Host Microbial Interactions ,HIV Antibodies ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,MESH: Antibodies, Neutralizing ,MESH: HIV-1 ,Epitopes ,MESH: Antibody-Dependent Cell Cytotoxicity ,Humans ,MESH: Broadly Neutralizing Antibodies ,Multidisciplinary ,MESH: Humans ,Host Microbial Interactions ,MESH: HIV Antibodies ,Antibody-Dependent Cell Cytotoxicity ,Virion ,env Gene Products, Human Immunodeficiency Virus ,virus diseases ,General Chemistry ,MESH: HIV Infections ,Antibodies, Neutralizing ,MESH: Cell Line ,MESH: T-Lymphocytes ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,HIV-1 ,MESH: Virion ,MESH: env Gene Products, Human Immunodeficiency Virus ,Broadly Neutralizing Antibodies - Abstract
Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) are promising molecules for therapeutic or prophylactic interventions. Beyond neutralization, bNAbs exert Fc-dependent functions including antibody-dependent cellular cytotoxicity and activation of the complement. Here, we show that a subset of bNAbs targeting the CD4 binding site and the V1/V2 or V3 loops inhibit viral release from infected cells. We combined immunofluorescence, scanning electron microscopy, transmission electron microscopy and immunogold staining to reveal that some bNAbs form large aggregates of virions at the surface of infected cells. This activity correlates with the capacity of bNAbs to bind to Env at the cell surface and to neutralize cell-free viral particles. We further show that antibody bivalency is required for viral retention, and that aggregated virions are neutralized. We have thus identified an additional antiviral activity of bNAbs, which block HIV-1 release by tethering viral particles at the surface of infected cells., O.S. is funded by Institut Pasteur, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), “TIMTAMDEN” ANR-14-CE14-0029, “CHIKV-Viro-Immuno” ANR-14-CE14-0015-01, and the Gilead HIV cure program. J.D. is funded by a Ph.D grant from the French Ministry of Higher Education and Research. H.M. is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), INSERM, ANRS, and Gilead HIV cure program. C.P. was supported by an ANRS fellowship. A.E. and S.F. are funded by Institut Pasteur, CNRS, and ANRS (ANRS-21020 AP2020-2). P.R. is funded by INSERM, Université de Tours and ANRS.
- Published
- 2022
26. Optimization of G‐Quadruplex Ligands through a SAR Study Combining Parallel Synthesis and Screening of Cationic Bis(acylhydrazones)
- Author
-
Oksana Reznichenko, Denis Leclercq, Jaime Franco Pinto, Liliane Mouawad, Valérie Gabelica, Anton Granzhan, 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), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), French Ministry of Higher Education, Research and Innovation (PhD fellowship, to OR), European Union's Horizon 2020 Framework Programme(Marie Skłodowska-Curie Grant Agreement No. 666003 through an IC-3i international PhD programme, to JFP), and benefited from access to Plateforme de BioPhysico-Chimie Structurale of the IECB (Univ. Bordeaux, CNRS UMS3033, Inserm US001) for native mass spectrometry., ANR-17-CE07-0004,DYCONAS,Chimie dynamique constitutionnelle pour les structures d'acides nucléiques(2017), GRANZHAN, Anton, and Chimie dynamique constitutionnelle pour les structures d'acides nucléiques - - DYCONAS2017 - ANR-17-CE07-0004 - AAPG2017 - VALID
- Subjects
G4 ligands ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,Nitrogen heterocycles ,[CHIM.THER] Chemical Sciences/Medicinal Chemistry ,Organic Chemistry ,Combinatorial chemistry ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,General Chemistry ,[CHIM.ORGA] Chemical Sciences/Organic chemistry ,G-quadruplexes ,N-acylhydrazones ,Catalysis - Abstract
International audience; G-quadruplexes (G4s), secondary structures adopted by guanine-rich DNA and RNA sequences, are implicated in numerous biological processes and have been suggested as potential drug targets. Accordingly, there is an increasing interest in developing high-throughput methods allowing the generation of congeneric series of G4-targeting molecules (“ligands”) and investigation of their interaction with the targets. Here, we developed an operationally simple method of parallel synthesis to generate “ready-to-screen” libraries of cationic acylhydrazones, a motif that we have previously identified as a promising scaffold for potent, biologically active G4 ligands. Combined with well-established screening techniques, such as fluorescence melting, this method enables rapid synthesis and screening of combinatorial libraries of potential G4 ligands. Following this protocol, we synthesized a combinatorial library of 90 bis(acylhydrazones) and screened it against five different nucleic acid structures. This way, we were able to analyze the structure-activity relationships within this series of G4 ligands, and identified three novel promising ligands whose interaction with G4-DNA of different topologies was carefully studied by a combination of several biophysical techniques, including native mass spectrometry, and molecular modeling.
- Published
- 2022
27. Ring size-reactivity relationship in radical ring-opening copolymerisation of thionolactones with vinyl pivalate
- Author
-
Oleksandr Ivanchenko, Stéphane Mazières, Rinaldo Poli, Simon Harrisson, Mathias Destarac, Interactions moléculaires et réactivité chimique et photochimique (IMRCP), 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 Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), 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)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), P3R - Polymères de Précision par Procédés Radicalaires (P3R), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT), Laboratoire de chimie de coordination (LCC), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and French Ministry of Higher Education, Research and Innovation
- Subjects
Polymers and Plastics ,Organic Chemistry ,[CHIM]Chemical Sciences ,Bioengineering ,Biochemistry - Abstract
International audience; The radical ring-opening copolymerisation of unsubstituted thionolactones of different ring sizes has been investigated. DFT calculations and experimental results show the importance of the stabilization of the intermediate ring-retained radical.
- Published
- 2022
28. Using a multiomics approach to unravel a septic shock specific signature in skeletal muscle
- Author
-
Baptiste Duceau, Michael Blatzer, Jean Bardon, Thibault Chaze, Quentin Giai Gianetto, Florence Castelli, François Fenaille, Lucie Duarte, Thomas Lescot, Christophe Tresallet, Bruno Riou, Mariette Matondo, Olivier Langeron, Pierre Rocheteau, Fabrice Chrétien, Adrien Bouglé, Neuropathologie expérimentale - Experimental neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Descartes - Paris 5 (UPD5), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Henri Mondor, Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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), MetaboHUB, CHU Saint-Antoine [AP-HP], Sorbonne Université (SU), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), GHU Paris Psychiatrie et Neurosciences, The study was funded by a grant of the French Ministry of Higher Education, Research and Innovation (Agence Nationale de la Recherche ANR-17-CE14-0035) to F. Chrétien. Drs A. Bouglé and B. Duceau were the recipients of a research fellowship grant from the Institut Pasteur (Paris, France) and Assistance Publique – Hôpitaux de Paris (Paris, France)., and ANR-17-CE14-0035,PUSHUPS,Etude de la dysfonction des cellules souches musculaires au cours du sepsis(2017)
- Subjects
Male ,Proteomics ,Multidisciplinary ,Critical Illness ,Sepsis ,[SDV]Life Sciences [q-bio] ,Humans ,Female ,Prospective Studies ,Muscle, Skeletal ,Shock, Septic - Abstract
Sepsis is defined as a dysregulated host response to infection leading to organs failure. Among them, sepsis induces skeletal muscle (SM) alterations that contribute to acquired-weakness in critically ill patients. Proteomics and metabolomics could unravel biological mechanisms in sepsis-related organ dysfunction. Our objective was to characterize a distinctive signature of septic shock in human SM by using an integrative multi-omics approach. Muscle biopsies were obtained as part of a multicenter non-interventional prospective study. Study population included patients in septic shock (S group, with intra-abdominal source of sepsis) and two critically ill control populations: cardiogenic shock (C group) and brain dead (BD group). The proteins and metabolites were extracted and analyzed by High-Performance Liquid Chromatography-coupled to tandem Mass Spectrometry, respectively. Fifty patients were included, 19 for the S group (53% male, 64 ± 17 years, SAPS II 45 ± 14), 12 for the C group (75% male, 63 ± 4 years, SAPS II 43 ± 15), 19 for the BD group (63% male, 58 ± 10 years, SAPS II 58 ± 9). Biopsies were performed in median 3 days [interquartile range 1–4]) after intensive care unit admission. Respectively 31 patients and 40 patients were included in the proteomics and metabolomics analyses of 2264 proteins and 259 annotated metabolites. Enrichment analysis revealed that mitochondrial pathways were significantly decreased in the S group at protein level: oxidative phosphorylation (adjusted p = 0.008); branched chained amino acids degradation (adjusted p = 0.005); citrate cycle (adjusted p = 0.005); ketone body metabolism (adjusted p = 0.003) or fatty acid degradation (adjusted p = 0.008). Metabolic reprogramming was also suggested (i) by the differential abundance of the peroxisome proliferator-activated receptors signaling pathway (adjusted p = 0.007), and (ii) by the accumulation of fatty acids like octanedioic acid dimethyl or hydroxydecanoic. Increased polyamines and depletion of mitochondrial thioredoxin or mitochondrial peroxiredoxin indicated a high level of oxidative stress in the S group. Coordinated alterations in the proteomic and metabolomic profiles reveal a septic shock signature in SM, highlighting a global impairment of mitochondria-related metabolic pathways, the depletion of antioxidant capacities, and a metabolic shift towards lipid accumulation.ClinicalTrial registration: NCT02789995. Date of first registration 03/06/2016.
- Published
- 2022
29. Edge-Fog-Cloud Computing Hierarchy for Improving Performance and Security of NB-IoT-Based Health Monitoring Systems
- Author
-
Daraghmi, Yousef-Awwad, Daraghmi, Eman Yaser, Daraghma, Raed, Fouchal, Hacene, Ayaida, Marwane, Université de Reims Champagne-Ardenne (URCA), Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), COMmunications NUMériques - IEMN (COMNUM - IEMN), INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), and Project Number: 02/2020 <<NBIOT>>, Fund name: Al Maqdisi programme, funder: the French-Palestinian Hubert Curien partnership and coordinated by the French Ministry for Europe and Foreign Affairs (MEAE), the French Ministry for Higher Education, Research and Innovation(MESRI), and by the Consulate General of France in Jerusalem.The authors would like to thank Palestine Technical University–Kadoorie and University de Reims Champagne Ardenne for supporting this research.
- Subjects
Narrow-Band IoT ,[SPI]Engineering Sciences [physics] ,edge computing ,communication delay ,cloud computing ,healthcare monitoring ,security ,fog computing - Abstract
International audience; This paper proposes a three-computing-layer architecture consisting of Edge, Fog, and Cloud for remote health vital signs monitoring. The novelty of this architecture is in using the Narrow-Band IoT (NB-IoT) for communicating with a large number of devices and covering large areas with minimum power consumption. Additionally, the architecture reduces the communication delay as the edge layer serves the health terminal devices with initial decisions and prioritizes data transmission for minimizing congestion on base stations. The paper also investigates different authentication protocols for improving security while maintaining low computation and transmission time. For data analysis, different machine learning algorithms, such as decision tree, support vector machines, and logistic regression, are used on the three layers. The proposed architecture is evaluated using CloudSim, iFogSim, and ns3-NB-IoT on real data consisting of medical vital signs. The results show that the proposed architecture reduces the NB-IoT delay by 59.9%, the execution time by an average of 38.5%, and authentication time by 35.1% for a large number of devices. This paper concludes that the NB-IoT combined with edge, fog, and cloud computing can support efficient remote health monitoring for large devices and large areas.
- Published
- 2022
30. Bandwidth Enhancement by Interconnecting Double Hexagonal Loops FSS
- Author
-
Nur Biha Mohamed Nafis, Mohamad Kamal A. Rahim, Mohamed Himdi, Universiti Teknologi Malaysia (UTM), Institut d'Électronique et des Technologies du numéRique (IETR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Mobility Grant from Rennes Metropole, European Union through the European Regional Development Fund, French Ministry of Higher Education and Research, Region Bretagne, CPER Project 2015-2020 SOPHIE/STIC, Ministry of Higher Education (MOHE) [FRGS/1/2021/TK0/UTM/01/7], Universite de Rennes 1, Ondes, School of Postgraduate Studies (SPS), Research Management Centre, School of Electrical Engineering [09G19], and Universiti Teknologi Malaysia (UTM), Johor Bahru [09G19]
- Subjects
[SPI]Engineering Sciences [physics] ,low cross-polarisation ,interconnect ,fractal ,mosaic frequency selective surface ,wideband - Abstract
International audience; The paper proposed a mosaic frequency selective surface (MFSS) which comprises of the integration between Koch fractal and a basic double hexagonal loop FSS. Through this integration, the bandwidth (BW) within the first bandstop and bandpass frequency responses achieved a wideband frequency response (fractional bandwidth (FBW) > 50%), while the BW of the second bandstop frequency response improved (FBW similar to 20%). The simulation process is conducted by using the CST software, and the FR4 substrate is used as the dielectric substrate for all of the proposed unit cells. With narrow trace width of the MFSS, the structural element can be further applied for optical transparency application with wideband filtering characteristics.
- Published
- 2022
31. Geometries, interaction energies and bonding in [Po(H2O)n]4+ and [PoCln]4-n complexes
- Author
-
Nadiya Zhutova, Florent Réal, Valérie Vallet, Rémi Maurice, 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), Physico-Chimie Moléculaire Théorique (PCMT), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), MITI of CNRS (80|Prime project MSM4Po), HPC resources from the CCIPL (‘‘Centre de calcul intensif des Pays de la Loire’’), French Ministry of Higher Education and Research, region Hauts de France council and European Regional Development Fund (ERDF) project CPER CLIMIBIO., ANR-11-LABX-0005,Cappa,Physiques et Chimie de l'Environnement Atmosphérique(2011), and ANR-16-IDEX-0004,ULNE,ULNE(2016)
- Subjects
Chemical Physics (physics.chem-ph) ,[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,Physics - Chemical Physics ,General Physics and Astronomy ,FOS: Physical sciences ,[PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph] ,Physical and Theoretical Chemistry - Abstract
International audience; Polonium (Z = 84) is one of the rarest elements on Earth. More than a century after its discovery, its chemistry remains poorly known and even basic questions have not yet been satisfactorily addressed. In this work, we perform a systematic study of the geometries, interactions energies and bonding in basic polonium(IV) species, namely the hydrated [Po(H2O)n]4+ and chlorinated [PoCl2]4-n complexes by means of gas-phase electronic structure calculations. We show that while up to nine water molecules can fit in the first coordination sphere of the polonium(IV) ion, its coordination sphere can already be filled with eight chloride ligands. Capitalising on previous theoretical studies, a focused methodological study based on interaction energies and bond distances allows us to validate the MP2/def2-TZVP level of theory for future ground-state studies. After discussing the similarities and differences between complexes with the same number of ligands, we perform topological analyses of the MP2 electron densities in the quantum theory of atoms in molecules (QTAIM) fashion. While the water complexes display typical signatures of closed-shell interactions, we reveal large Po–Cl delocalisation indices, especially in the hypothetical [PoCl]3+ complex. This “enhanced” covalency opens the way for a significant spin–orbit coupling (SOC) effect on the corresponding bond distance, which has been studied using two independent approaches (i.e. one a priori and one a posteriori). We finally conclude by stressing that while the SOC may not affect much the geometries of high-coordinated polonium(IV) complexes, it should definitely not be neglected in the case of low-coordinated ones.
- Published
- 2022
32. Risk-aware linear bandits with convex loss
- Author
-
Saux, Patrick, Maillard, Odalric-Ambrym, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Scool (Scool), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and French National Research Agency, the French Ministry of Higher Education and Research, Inria, the MEL and the I-Site ULNE regarding project R-PILOTE-19-004-APPRENF and Bandits For Health (B4H).
- Subjects
FOS: Computer and information sciences ,Computer Science - Machine Learning ,risk-awareness ,online gradient descent ,[STAT.ML]Statistics [stat]/Machine Learning [stat.ML] ,Statistics - Machine Learning ,Machine Learning (stat.ML) ,Contextual bandit ,elicitable risk measures ,Machine Learning (cs.LG) ,UCB - Abstract
International audience; In decision-making problems such as the multi-armed bandit, an agent learns sequentially by optimizing a certain feedback. While the mean reward criterion has been extensively studied, other measures that reflect an aversion to adverse outcomes, such as mean-variance or conditional value-at-risk (CVaR), can be of interest for critical applications (healthcare, agriculture). Algorithms have been proposed for such risk-aware measures under bandit feedback without contextual information. In this work, we study contextual bandits where such risk measures can be elicited as linear functions of the contexts through the minimization of a convex loss. A typical example that fits within this framework is the expectile measure, which is obtained as the solution of an asymmetric least-square problem. Using the method of mixtures for supermartingales, we derive confidence sequences for the estimation of such risk measures. We then propose an optimistic UCB algorithm to learn optimal risk-aware actions, with regret guarantees similar to those of generalized linear bandits. This approach requires solving a convex problem at each round of the algorithm, which we can relax by allowing only approximated solution obtained by online gradient descent, at the cost of slightly higher regret. We conclude by evaluating the resulting algorithms on numerical experiments.
- Published
- 2022
33. Small RNA-sequencing reveals the involvement of microRNA-132 in benzo[a]pyrene-induced toxicity in primary human blood cells
- Author
-
Rima Souki, Jérémy Amosse, Valentine Genêt, Morgane Le Gall, Benjamin Saintpierre, Franck Letourneur, Anne Maître, Christine Demeilliers, Eric Le Ferrec, Dominique Lagadic-Gossmann, Normand Podechard, Lydie Sparfel, 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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Environnement et Prévention en Santé des Populations (TIMC-EPSP ), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), 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 Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-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 Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), and The funding of this work was supported by The French National Research Program for Environmental and Occupational Health of Anses (2019/1/010) Rima Souki had a doctoral fellowship from the French Ministry for Higher Education and Research. Jeremy Amosse was a post-doctoral recipient from Anses. We are also thankful to the faculty of Pharmacy of Rennes, for funding the extended contract of Rima Souki.
- Subjects
Benzo[a]pyrene ,Cytochromes P-450 1A1 and 1B1 ,Peripheral blood mononuclear cells ,[SDV]Life Sciences [q-bio] ,Health, Toxicology and Mutagenesis ,miR-132–3p ,[SDE]Environmental Sciences ,General Medicine ,Toxicology ,Pollution ,Aryl hydrocarbon receptor ,Polycyclic aromatic hydrocarbons ,microRNAs - Abstract
International audience; Polycyclic aromatic hydrocarbons (PAHs) are widely distributed environmental contaminants, triggering deleterious effects such as carcinogenicity and immunosuppression, and peripheral blood mononuclear cells (PBMCs) are among the main cell types targeted by these pollutants. In the present study, we sought to identify the expression profiles and function of miRNAs, gene regulators involved in major cellular processes recently linked to environmental pollutants, in PBMC-exposed to the prototypical PAH, benzo[a]pyrene (B[a]P). Using small RNA deep sequencing, we identified several B[a]P-responsive miRNAs. Bioinformatics analyses showed that their predicted targets could modulate biological processes relevant to cell death and survival. Further studies of the most highly induced miRNA, miR-132, showed that its up-regulation by B[a]P was time- and dose-dependent and required aryl hydrocarbon receptor (AhR) activation. By evaluating the role of miR-132 in B[a]P-induced cell death, we propose a mechanism linking B[a]P-induced miR-132 expression and cytochromes P-450 (CYPs) 1A1 and 1B1 mRNA levels, which could contribute to the apoptotic response of PBMCs. Altogether, this study increases our understanding of the roles of miRNAs induced by B[a]P and provides the basis for further investigations into the mechanisms of gene expression regulation by PAHs.
- Published
- 2023
34. DNA nuclear targeting sequences for enhanced non-viral gene transfer: An in vitro and in vivo study
- Author
-
Tristan Montier, Philippe Guégan, Sandrine Quemener, Kévin Pluchon, Juliette Ropars, Chantal Pichon, Tanguy Haute, Yann Thierry Le Guen, Tony Le Gall, Patrick Midoux, Gestionnaire, Hal Sorbonne Université, monopDNA-Nanoparticules Virus-Inspirées pour transfert de gènes. - - VINP2017 - ANR-17-CE18-0015 - AAPG2017 - VALID, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Parisien de Chimie Moléculaire (IPCM), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Chimie des polymères (LCP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Parisien de Chimie Moléculaire (IPCM), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), This work was funded by grants from the AFM – Association Française contre les Myopathies (project no. AFM2017#20609, AFM, Evry, France), the ANR – Agence Nationale de la Recherche (project no. ANR-17-CE18-0015-03, 'monopDNA-Nanoparticules Virus-Inspirées pour transfert de gènes', ANR, Paris, France), the Association de Transfusion Sanguine et de Biogénétique Gaétan Saleün (Brest, France), and the Région Bretagne (France). The Service Général des Plateformes, Animalerie Commune (Brest, France) and SynNanoVect (Brest-Rennes, France) are also acknowledged. Y.T.L.G. was a recipient of a PhD fellowship from the French Ministry of Higher Education, Research and Innovation., ANR-17-CE18-0015,VINP,monopDNA-Nanoparticules Virus-Inspirées pour transfert de gènes.(2017), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), and Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD)
- Subjects
0301 basic medicine ,[SDV]Life Sciences [q-bio] ,RM1-950 ,NF-κB ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,plasmid DNA ,In vivo ,Drug Discovery ,skeletal muscle ,Transcription factor ,hydrodynamic limb vein injection ,Transfection ,nuclear import ,In vitro ,Cell biology ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,chemistry ,transfection ,Cell culture ,030220 oncology & carcinogenesis ,Nucleic acid ,Molecular Medicine ,Therapeutics. Pharmacology ,Nuclear transport ,DNA - Abstract
International audience; An important bottleneck for non-viral gene transfer commonly relates to translocation of nucleic acids into the nuclear compartment of target cells. So-called 3NFs are optimized short nucleotide sequences able to interact with the transcription factor nuclear factor κB (NF-κB), which can enhance the nuclear import of plasmid DNA (pDNA) carrying such motifs. In this work, we first designed a consistent set of six pDNAs featuring a common backbone and only varying in their 3NF sequences. These constructions were then transfected under various experimental settings. In vitro, cationic polymer-assisted pDNA delivery in five human-derived cell lines showed the potential advantage of 3NF carrying pDNA in diverse cellular contexts. In vivo, naked pDNAs were hydrodynamically delivered to muscle hindlimbs in healthy mice; this direct accurate comparative (in the absence of any gene carrier) revealed modest but consistent trends in favor of the pDNAs equipped with 3NF. In summary, the results reported emphasize the implications of various parameters on NF-κB-mediated pDNA nuclear import; under specific conditions, 3NF can provide modest to substantial advantages for pDNA gene transfer, in vitro as well as in vivo. This study thus further underscores the potential of optimized nuclear import for more efficient non-viral gene transfer applications.
- Published
- 2021
35. IRF8 regulates efficacy of therapeutic anti-CD20 monoclonal antibodies
- Author
-
Ludivine Grzelak, Ferdinand Roesch, Amaury Vaysse, Anne Biton, Rachel Legendre, Françoise Porrot, Pierre‐Henri Commère, Cyril Planchais, Hugo Mouquet, Marco Vignuzzi, Timothée Bruel, Olivier Schwartz, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Institut Pasteur [Paris] (IP), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Populations virales et Pathogenèse - Viral Populations and Pathogenesis, Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM, IDISCOVR European Health Emergency Preparedness and Response Authority (HERA), French Ministry of Higher Education, Research and Innovation, ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), and ANR-21-CO14-0007,CoronaMito,Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale(2021)
- Subjects
Immunology ,Antineoplastic Agents ,anti-CD20 monoclonal antibodies ,Antigens, CD20 ,IRF8 ,DLBCL ,Interferon Regulatory Factors ,Immunology and Allergy ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Humans ,RNA ,CD20 protein ,Rituximab ,CRISPR/Cas9 - Abstract
International audience; Anti-CD20 monoclonal antibodies such as Rituximab, Ofatumumab, and Obinutuzumab are widely used to treat lymphomas and autoimmune diseases. They act by depleting B cells, mainly through Fc-dependent effectors functions. Some patients develop resistance to treatment but the underlying mechanisms are poorly understood. Here, we performed a genome-wide CRISPR/Cas9 screen to identify genes regulating the efficacy of anti-CD20 antibodies. We used as a model the killing of RAJI B cells by Rituximab through complement-dependent-cytotoxicity (CDC). As expected, the screen identified MS4A1, encoding CD20, the target of Rituximab. Among other identified genes, the role of Interferon Regulatory Factor 8 (IRF8) was validated in two B-cell lines. IRF8 KO also decreased the efficacy of antibody-dependent cellular cytotoxicity and phagocytosis (ADCC and ADCP) induced by anti-CD20 antibodies. We further show that IRF8 is necessary for efficient CD20 transcription. Levels of IRF8 and CD20 RNA or proteins correlated in normal B cells and in hundreds of malignant B cells. Therefore, IRF8 regulates CD20 expression and controls the depleting capacity of anti-CD20 antibodies. Our results bring novel insights into the pathways underlying resistance to CD20-targeting immunotherapies.
- Published
- 2022
36. Differential Genetic Strategies of Burkholderia vietnamiensis and Paraburkholderia kururiensis for Root Colonization of Oryza sativa subsp. japonica and O. sativa subsp. indica , as Revealed by Transposon Mutagenesis Sequencing
- Author
-
Wallner, Adrian, Busset, Nicolas, Lachat, Joy, Guigard, Ludivine, King, Eoghan, Rimbault, Isabelle, Mergaert, Peter, Béna, Gilles, Moulin, Lionel, Plant Health Institute of Montpellier (UMR PHIM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-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), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), CGIAR research program (CRP) RICE, Ph.D. fellowships from the French Ministry of Higher Education, Research and Innovation, and ANR-19-CE20-0007,BURKADAPT,Etude de l'adaptation à l'hôte chez les Burkholderia symbiotiques et pathogènes des eucaryotes(2019)
- Subjects
Burkholderia vietnamiensis ,Rrice ,Tn-seqPGP ,Paraburkholderia kururiensis ,root colonization ,[SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy - Abstract
International audience; Burkholderiaceae are frequent and abundant colonizers of the rice rhizosphere and interesting candidates to investigate for growth promotion. Species of Paraburkholderia have repeatedly been described to stimulate plant growth.Burkholderia vietnamiensis LMG10929 and Paraburkholderia kururiensis M130 are bacterial rice growth-promoting models. Besides this common ecological niche, species of the Burkholderia genus are also found as opportunistic human pathogens, while Paraburkholderia species are mostly environmental and plant associated. In this study, we compared the genetic strategies used by B. vietnamiensis and P. kururiensis to colonize two subspecies of their common host, Oryza sativa subsp. japonica (cv. Nipponbare) and O. sativa subsp. indica (cv. IR64). We used high-throughput screening of transposon insertional mutant libraries (Tn-seq) to infer which genetic elements have the highest fitness contribution during root surface colonization at 7 days postinoculation. Overall, we detected twice more genes in B. vietnamiensis involved in rice root colonization than in P. kururiensis, including genes contributing to the tolerance of plant defenses, which suggests a stronger adverse reaction of rice toward B. vietnamiensis than toward P. kururiensis. For both strains, the bacterial fitness depends on a higher number of genes when colonizing indica rice compared to japonica. These divergences in host pressure on bacterial adaptation could be partly linked to the cultivars' differences in nitrogen assimilation. We detected several functions commonly enhancing root colonization in both bacterial strains, e.g., Entner-Doudoroff (ED) glycolysis. Less frequently and more strain specifically, we detected functions limiting root colonization such as biofilm production in B. vietnamiensis and quorum sensing in P. kururiensis. The involvement of genes identified through the Tn-seq procedure as contributing to root colonization, i.e., ED pathway, c-di-GMP cycling, and cobalamin synthesis, was validated by directed mutagenesis and competition with wild-type (WT) strains in rice root colonization assays. IMPORTANCE Burkholderiaceae are frequent and abundant colonizers of the rice rhizosphere and interesting candidates to investigate for growth promotion. Species of Paraburkholderia have repeatedly been described to stimulate plant growth. However, the closely related Burkholderia genus includes both beneficial and phytopathogenic species, as well as species able to colonize animal hosts and cause disease in humans. We need to understand to what extent the bacterial strategies used for the different biotic interactions differ depending on the host and if strains with agricultural potential could also pose a threat toward other plant hosts or humans. To start answering these questions, we used in this study transposon sequencing to identify genetic traits in Burkholderia vietnamiensis and Paraburkholderia kururiensis that contribute to the colonization of two different rice varieties. Our results revealed large differences in the fitness gene sets between the two strains and between the host plants, suggesting a strong specificity in each bacterium-plant interaction.
- Published
- 2022
37. The emergence, spread and vanishing of a French SARS-CoV-2 variant exemplifies the fate of RNA virus epidemics and obeys the Mistigri rule
- Author
-
Philippe Colson, Philippe Gautret, Jeremy Delerce, Hervé Chaudet, Pierre Pontarotti, Patrick Forterre, Raphael Tola, Marielle Bedotto, Léa Delorme, Wahiba Bader, Anthony Levasseur, Jean‐Christophe Lagier, Matthieu Million, Nouara Yahi, Jacques Fantini, Bernard La Scola, Pierre‐Edouard Fournier, Didier Raoult, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Unité de Neurobiologie des canaux Ioniques et de la Synapse (UNIS - Inserm U1072), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the French Government under the 'Investments for the Future' program managed by the National Agency for Research (ANR) (Méditerranée-Infection 10-IAHU-03), by the Région Provence Alpes Côte d'Azur and European funding FEDER PRIMMI (Fonds Européen de Développement Régional-Plateformes de Recherche et d'Innovation Mutualisées Méditerranée Infection) (FEDER PA 0000320 PRIMMI), and by the French Ministry of Higher Education, Research and Innovation (Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation) and the French Ministry of Solidarity and Health (Ministère des Solidarités et de la Santé)., ANR-10-IAHU-0003,Méditerranée Infection,I.H.U. Méditerranée Infection(2010), Pontarotti, Pierre, Instituts Hospitalo-Universitaires - I.H.U. Méditerranée Infection - - Méditerranée Infection2010 - ANR-10-IAHU-0003 - IAHU - VALID, and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA)
- Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,variants ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,ORF8 ,Pangolin B.1.1.160 ,epidemic ,SARS‐CoV‐2 ,Infectious Diseases ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Virology ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Marseille‐4 ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie - Abstract
International audience; The nature and dynamics of mutations associated with the emergence, spread, and vanishing of SARS-CoV-2 variants causing successive waves are complex. We determined the kinetics of the most common French variant (“Marseille-4”) for 10 months since its onset in July 2020. Here, we analyzed and classified into subvariants and lineages 7453 genomes obtained by next-generation sequencing. We identified two subvariants, Marseille-4A, which contains 22 different lineages of at least 50 genomes, and Marseille-4B. Their average lifetime was 4.1 ± 1.4 months, during which 4.1 ± 2.6 mutations accumulated. Growth rate was 0.079 ± 0.045, varying from 0.010 to 0.173. Most of the lineages exhibited a bell-shaped distribution. Several beneficial mutations at unpredicted sites initiated a new outbreak, while the accumulation of other mutations resulted in more viral heterogenicity, increased diversity and vanishing of the lineages. Marseille-4B emerged when the other Marseille-4 lineages vanished. Its ORF8 gene was knocked out by a stop codon, as reported in SARS-CoV-2 of mink and in the Alpha variant. This subvariant was associated with increased hospitalization and death rates, suggesting that ORF8 is a nonvirulence gene. We speculate that the observed heterogenicity of a lineage may predict the end of the outbreak.
- Published
- 2022
38. Topoisomerase VI participates in an insulator-like function that prevents H3K9me2 spreading
- Author
-
Louis-Valentin Méteignier, Cécile Lecampion, Florent Velay, Cécile Vriet, Laura Dimnet, Martin Rougée, Christian Breuer, Ludivine Soubigou-Taconnat, Keiko Sugimoto, Fredy Barneche, Christophe Laloi, Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-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), Luminy Génétique et Biophysique des Plantes (LGBP), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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), RIKEN Center for Sustainable Resource Science [Yokohama] (RIKEN CSRS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Velux Stiftung (Switzerland)., L.D. was supported by the Commissariat à l’énergie atomique et aux énergies alternatives and Région Provence-Alpes-Côte d’Azur. F.V. is a recipient of a PhD fellowship from the French Ministry of Higher Education, Research and Innovation., Mass spectrometry analysis was performed at the IMM platform supported by a grant from the Groupement d’Intérêt Scientifique (GIS) Infrastrutures en Biologie Sante et Agronomie (IBiSA)., ANR-14-CE02-0010,SLOSAM,Signalisation du stress photooxydant dans les mécanismes d'acclimatation des plantes aux changements climatiques(2014), ANR-10-LABX-0054,MEMOLIFE,Memory in living systems: an integrated approach(2010), ANR-18-CE13-0004,ChromaLight,Functional links between nuclear architecture and epigenome reprogramming during plant adaptive responses to light(2018), ANR-17-CE12-0026,RiboStress,Interconnections génétiques, épigénétiques et protéiques au cours de la réorganisation fonctionnelle du nucléole et des réponses aux stress(2017), ANR-10-LABX-0040,SPS,Saclay Plant Sciences(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-10-JCJC-1205,CHROS,CHromatine et ROS : Rôle du facteur de remodelage de la chromatine topoisomérase VI dans la réponse transcriptionnelle des plantes à l'oxygène singulet et autres formes actives de l'oxygène lors de conditions de stress abiotique.(2010), BARNECHE, Fredy, Appel à projets générique - Signalisation du stress photooxydant dans les mécanismes d'acclimatation des plantes aux changements climatiques - - SLOSAM2014 - ANR-14-CE02-0010 - Appel à projets générique - VALID, Memory in living systems: an integrated approach - - MEMOLIFE2010 - ANR-10-LABX-0054 - LABX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Functional links between nuclear architecture and epigenome reprogramming during plant adaptive responses to light - - ChromaLight2018 - ANR-18-CE13-0004 - AAPG2018 - VALID, Interconnections génétiques, épigénétiques et protéiques au cours de la réorganisation fonctionnelle du nucléole et des réponses aux stress - - RiboStress2017 - ANR-17-CE12-0026 - AAPG2017 - VALID, Saclay Plant Sciences - - SPS2010 - ANR-10-LABX-0040 - LABX - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Jeunes Chercheuses et Jeunes Chercheurs - CHromatine et ROS : Rôle du facteur de remodelage de la chromatine topoisomérase VI dans la réponse transcriptionnelle des plantes à l'oxygène singulet et autres formes actives de l'oxygène lors de conditions de stress abiotique. - - CHROS2010 - ANR-10-JCJC-1205 - JCJC - VALID, and Aix Marseille Université (AMU)
- Subjects
Topoisomerase ,Multidisciplinary ,Arabidopsis Proteins ,[SDV]Life Sciences [q-bio] ,Arabidopsis ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Methionine Adenosyltransferase ,Chromatin ,Heterochromatin spreading ,Euchromatin ,Histones ,[SDV] Life Sciences [q-bio] ,Topoisomerase VI ,[SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics ,[SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding ,Epigenome ,DNA Topoisomerases, Type II ,Heterochromatin ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,[SDV.GEN.GPL] Life Sciences [q-bio]/Genetics/Plants genetics ,Euchromatin islands ,DNA Transposable Elements ,Insulator - Abstract
The organization of the genome into transcriptionally active and inactive chromatin domains requires well-delineated chromatin boundaries and insulator functions in order to maintain the identity of adjacent genomic loci with antagonistic chromatin marks and functionality. In plants that lack known chromatin insulators, the mechanisms that prevent heterochromatin spreading into euchromatin remain to be identified. Here, we show that DNA Topoisomerase VI participates in a chromatin boundary function that safeguards the expression of genes in euchromatin islands within silenced heterochromatin regions. While some transposable elements are reactivated in mutants of the Topoisomerase VI complex, genes insulated in euchromatin islands within heterochromatic regions of the Arabidopsis thaliana genome are specifically down-regulated. H3K9me2 levels consistently increase at euchromatin island loci and decrease at some transposable element loci. We further show that Topoisomerase VI physically interacts with S-adenosylmethionine synthase methionine adenosyl transferase 3 (MAT3), which is required for H3K9me2. A Topoisomerase VI defect affects MAT3 occupancy on heterochromatic elements and its exclusion from euchromatic islands, thereby providing a possible mechanistic explanation to the essential role of Topoisomerase VI in the delimitation of chromatin domains.
- Published
- 2022
39. SHLD1 is dispensable for 53BP1-dependent V(D)J recombination but critical for productive class switch recombination
- Author
-
Estelle Vincendeau, Wenming Wei, Xuefei Zhang, Cyril Planchais, Wei Yu, Hélène Lenden-Hasse, Thomas Cokelaer, Juliana Pipoli da Fonseca, Hugo Mouquet, David J. Adams, Frederick W. Alt, Stephen P. Jackson, Gabriel Balmus, Chloé Lescale, Ludovic Deriano, Vincendeau, Estelle [0000-0002-0231-1609], Zhang, Xuefei [0000-0002-1873-6679], Yu, Wei [0000-0002-1777-5254], Cokelaer, Thomas [0000-0001-6286-1138], Adams, David J [0000-0001-9490-0306], Jackson, Stephen P [0000-0001-9317-7937], Balmus, Gabriel [0000-0003-2872-4468], Lescale, Chloé [0000-0003-0622-1149], Deriano, Ludovic [0000-0002-9673-9525], Apollo - University of Cambridge Repository, Intégrité du génome, immunité et cancer - Genome integrity, Immunity and Cancer, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Howard Hughes Medical Institute (HHMI), Peking University [Beijing], Immunologie humorale - Humoral Immunology, Biomics (plateforme technologique), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, The Wellcome Trust Sanger Institute [Cambridge], University of Cambridge [UK] (CAM), The Deriano laboratory is funded by Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (Inserm), Wordwide Cancer Research (grant # 19-0333), Ligue Nationale Contre le Cancer (Equipe labellisée 2019), and Institut National du Cancer (INCa, grant # PLBIO19-122). E.V. is supported by the French Ministry of Higher Education, Research, and Innovation (Doctoral School Bio Sorbonne Paris Cité) and by the Fondation pour la Recherche Médicale. W.W. is part of the Pasteur–Paris University International Ph.D. program and received funding from the CNBG company, China. The Balmus laboratory at the UK DRI is funded by the Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. Research in the Jackson laboratory is funded by Cancer Research UK (CRUK) program grant DRCPGM\100005 and core grant C6946/A24843, Wellcome Investigator award 206388/Z/17/Z and core grant 203144, and ERC Synergy award 855741. S.P.J. receives a salary from the University of Cambridge. F.W.A is an investigator of the Howard Hughes Medical Institute. H.M. received core grants from the Institut Pasteur, the INSERM and the Milieu Intérieur Program (ANR-10-LABX-69-01)., We thank the Wellcome Trust Sanger Institute Mouse Genetics Project (Sanger MGP) and its funders for providing the mutant mouse line (Allele: Shld1em1(IMPC)Wtsi), and INFRAFRONTIER/EMMA. We thank the Institut Pasteur animal facility, specifically Quentin Mille, Jeromine Rohard Blanco, and Franck Bourgade for mouse weighing. We thank Jean-Pierre de Villartay for providing the CD21-Cre3a line and Klaus Rajewsky and MGC for permission to use the line. We thank Michela Di Virgilio for providing 53BP1 knockout animals and Junjie Chen for permission to use them. We thank members of the Deriano lab for their discussion and technical help. We thank Bernardo Reina-San-Martin for the discussion and advices. We thank Christopher Carnie for the discussion on the design of SHLD1 mutant sites., ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), and Jackson, Stephen [0000-0001-9317-7937]
- Subjects
DNA End-Joining Repair ,MESH: V(D)J Recombination ,[SDV]Life Sciences [q-bio] ,MESH: DNA Breaks, Double-Stranded ,General Physics and Astronomy ,13/106 ,45/23 ,631/250/2152/2497 ,631/250/2152/2498 ,General Biochemistry, Genetics and Molecular Biology ,13/1 ,13/21 ,DNA Breaks, Double-Stranded ,631/337/1427/2122 ,Multidisciplinary ,45/71 ,45 ,fungi ,article ,45/77 ,General Chemistry ,MESH: DNA End-Joining Repair ,Immunoglobulin Class Switching ,V(D)J Recombination ,49 ,DNA-Binding Proteins ,13/31 ,enzymes and coenzymes (carbohydrates) ,MESH: Immunoglobulin Class Switching ,631/337/149 ,MESH: DNA-Binding Proteins - Abstract
Funder: Ligue Nationale Contre le Cancer, SHLD1 is part of the Shieldin (SHLD) complex, which acts downstream of 53BP1 to counteract DNA double-strand break (DSB) end resection and promote DNA repair via non-homologous end-joining (NHEJ). While 53BP1 is essential for immunoglobulin heavy chain class switch recombination (CSR), long-range V(D)J recombination and repair of RAG-induced DSBs in XLF-deficient cells, the function of SHLD during these processes remains elusive. Here we report that SHLD1 is dispensable for lymphocyte development and RAG-mediated V(D)J recombination, even in the absence of XLF. By contrast, SHLD1 is essential for restricting resection at AID-induced DSB ends in both NHEJ-proficient and NHEJ-deficient B cells, providing an end-protection mechanism that permits productive CSR by NHEJ and alternative end-joining. Finally, we show that this SHLD1 function is required for orientation-specific joining of AID-initiated DSBs. Our data thus suggest that 53BP1 promotes V(D)J recombination and CSR through two distinct mechanisms: SHLD-independent synapsis of V(D)J segments and switch regions within chromatin, and SHLD-dependent protection of AID-DSB ends against resection.
- Published
- 2022
- Full Text
- View/download PDF
40. Defective type I interferon immunity is associated with increasing COVID-19 severity
- Author
-
Darragh Duffy, Nikaïa SMITH, Céline Possémé, Vincent Bondet, Jamie Sugrue, Liam Townsend, Bruno Charbit, Vincent Rouilly, Violaine Saint-André, Tom Dott, Andre Rodriguez Pozo, Nader Yatim, Olivier Schwartz, Minerva Cervantes-Gonzales, Jade Ghosn, Paul Bastard, Jean-Laurent Casanova, Tali-Anne Szwebel, Benjamin Terrier, Niall Conlon, Cliona O'Farrelly, Cliona Ni Cheallaigh, Nollaig Bourke, Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Trinity College Dublin, Datactix, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], St James' Hospital, This study was supported by the 'URGENCE COVID-19' fundraising campaign the Institut Pasteur (CoVarImm and Steroid Response), from the Agence Nationale de la Recherche (ANR-flash COVID-19), by the Laboratoire d’Excellence ‘Milieu Intérieur’ (grant no. ANR-10-LABX-69-01), the Fonds IMMUNOV for Innovation in Immunopathology, and Science Foundation Ireland. We thank the STTAR-Bioresource of TCD-SJH-TUH COVID-19 bioresource which supported collection of patient samples. NS is a recipient of the Pasteur-Roux-Cantarini Fellowship. COF, NC and CNC are part-funded by a Science Foundation Ireland (SFI) grant, Grant Code 20/SPP/3685. LT is supported by the Irish Clinical Academic Training (ICAT) Programme, supported by the Wellcome Trust and the Health Research Board (Grant Number 203930/B/16/Z), the Health Service Executive, National Doctors Training and Planning and the Health and Social Care, Research and Development Division, Northern Ireland. N.B. is funded under the Science Foundation Ireland Phase 2 COVID-19 Rapid Response Call (20/COV/8487) and the Health Research Board COVID-19 Rapid Response Call (COV19e2020e053). The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), ANR AABIFNCOV (ANR-20-CO11-0001) and ANR GenMISC (ANR-21-COVR-0039) projects, the European Union’s Horizon 2020 research and innovation programme under grant agreement No 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, The French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM and the University of Paris. PB was supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller)., We thank the UTechS CB of the Center for Translational Research, Institut Pasteur for supporting Luminex and Nanostring analysis. We acknowledge all health-care workers involved in the diagnosis and treatment of patients in Hopital Cochin, Hopital Bichat, and St James’s Hospital Dublin., ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), Institut Pasteur [Paris]-Université Paris Cité (UPC), Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)
- Subjects
[SDV]Life Sciences [q-bio] - Abstract
Host immunity to infection with SARS-CoV-2 is highly variable, dictating diverse clinical outcomes ranging from asymptomatic to severe disease and death. We previously reported that reduced blood type I interferon (IFN-I) in severe COVID-19 patients preceded clinical worsening. These results were supported by studies which identified genetic mutations in loci of the TLR3- or TLR7-dependent IFN-I pathways, or autoantibodies neutralizing IFNα or IFNω, as major risk factors for development of severe and critical COVID-19 pneumonia. Here, we analyzed a range of IFN-I associated responses in patient cohorts with different severities of COVID-19, showing that baseline plasma IFNα measures differed significantly according to the immunoassay used, as well as timing of sampling, the IFNα subtype measured, and the presence of autoantibodies. We then compared immune responses induced by ex vivo stimulation between non-hospitalized moderate cases (n=27) and hospitalized (n=17) adult patients that required oxygen supplementation. This showed a consistently reduced induction of IFN-I proteins in hospitalized COVID-19 patients upon stimulation, that was not associated with detectable neutralizing autoantibodies against IFNα or IFNω. We confirmed the poor induction of IFN-I in an independent patient cohort (n=33), and showed it was more pronounced with severe disease. Intracellular proteomic analysis showed that while monocyte numbers were increased in hospitalized COVID-19 patients, they did not secrete IFN-I in response to stimulation. This was further confirmed by ex vivo whole blood stimulation with IFN-I which induced a transcriptomic response associated with inflammation in hospitalized COVID-19 patients, that was not seen in controls or non-hospitalized moderate cases. These results may explain the dichotomy of the poor clinical response to IFN-I based treatments in late stage COVID-19, despite the critical importance of IFN-I in early acute infection. An improved understanding of such variable responses to treatment may help to identify potential alternative therapeutic strategies.
- Published
- 2022
41. Highlighting the positive aspects of being a PhD student
- Author
-
Martin Philippe-Lesaffre, Clara Marino, Léo Lusardi, Camille Bernery, Elena Angulo, Elsa Bonnaud, Loreleï Guéry, Eléna Manfrini, Anna Turbelin, Céline Albert, Ugo Arbieu, Franck Courchamp, Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Estación Biológica de Doñana (EBD), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Plant Health Institute of Montpellier (UMR PHIM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-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), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Smithsonian Conservation Biology Institute, Senckenberg Biodiversity and Climate Research Centre (SBiK-F), Goethe-Universität Frankfurt am Main-Senckenberg – Leibniz Institution for Biodiversity and Earth System Research - Senckenberg Gesellschaft für Naturforschung, Leibniz Association-Leibniz Association, PhD students were funded by the French Ministry of Higher Education (CB, LL, CM, MPL), postdocs were funded by the Senckenberg Biodiversity and Climate Research Centre (UA), the Biodiversa ERA-Net AlienScenario project (AT), and the AXA Research Fund Chair for Invasion Biology of University Paris-Saclay (EA, CA, EM), and Tenured academics salary were funded by the University Paris-Saclay (EB), the CIRAD (LG) and the CNRS (FC). MPL was also funded as an intern by the ENS Paris-Saclay during part of the project.
- Subjects
C10 - Enseignement ,General Immunology and Microbiology ,[SDV]Life Sciences [q-bio] ,General Neuroscience ,Étudiant ,General Medicine ,Enseignement supérieur ,General Biochemistry, Genetics and Molecular Biology ,[SHS]Humanities and Social Sciences ,Université ,institution de recherche ,[SDE]Environmental Sciences ,Humans ,Students - Abstract
International audience; Articles about doing a PhD tend to focus on the difficulties faced by research students. Here we argue that the scientific community should also highlight the positive elements of the PhD experience.
- Published
- 2022
42. A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes
- Author
-
Paul Bastard, Kuang-Chih Hsiao, Qian Zhang, Jeremy Choin, Emma Best, Jie Chen, Adrian Gervais, Lucy Bizien, Marie Materna, Christine Harmant, Maguelonne Roux, Nicola L. Hawley, Daniel E. Weeks, Stephen T. McGarvey, Karla Sandoval, Carmina Barberena-Jonas, Consuelo D. Quinto-Cortés, Erika Hagelberg, Alexander J. Mentzer, Kathryn Robson, Boubacar Coulibaly, Yoann Seeleuthner, Benedetta Bigio, Zhi Li, Gilles Uzé, Sandra Pellegrini, Lazaro Lorenzo, Zineb Sbihi, Sylvain Latour, Marianne Besnard, Tiphaine Adam de Beaumais, Evelyne Jacqz Aigrain, Vivien Béziat, Ranjan Deka, Litara Esera Tulifau, Satupa‘itea Viali, Muagututi‘a Sefuiva Reupena, Take Naseri, Peter McNaughton, Vanessa Sarkozy, Jane Peake, Annaliesse Blincoe, Sarah Primhak, Simon Stables, Kate Gibson, See-Tarn Woon, Kylie Marie Drake, Adrian V.S. Hill, Cheng-Yee Chan, Richard King, Rohan Ameratunga, Iotefa Teiti, Maite Aubry, Van-Mai Cao-Lormeau, Stuart G. Tangye, Shen-Ying Zhang, Emmanuelle Jouanguy, Paul Gray, Laurent Abel, Andrés Moreno-Estrada, Ryan L. Minster, Lluis Quintana-Murci, Andrew C. Wood, Jean-Laurent Casanova, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University [New York], Human genetics of infectious diseases: Complex predisposition (Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Howard Hughes Medical Institute (HHMI), University of Auckland [Auckland], Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège de France - Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Langebio (CINVESTAV), University of New South Wales [Sydney] (UNSW), Sydney Children's hospital, Garvan Institute of medical research, UNSW Faculty of Medicine [Sydney], Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD), Auckland City Hospital, Canterbury Health Laboratories, University of Oxford, University of Queensland [Brisbane], Brown University, Ministry of Health [Samoa], Tupua Tamasese Meaole Hospital (TTM), University of Cincinnati (UC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Institut Gustave Roussy (IGR), Centre Hospitalier de Polynésie Française, Signalisation des Cytokines - Cytokine Signaling, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Oslo (UiO), National Laboratory of Genomics for Biodiversity (LANGEBIO), Centro de Investigacion y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Yale University [New Haven], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Shanghai Jiaotong University, Murdoch Children's Research Institute (MCRI), The laboratory of V.-M. Cao-Lormeau is supported by MATAEA grant no. 03557/MED/REC_29/05/2019 (Délégation à la recherche de la Polynésie française). The Laboratory of Human Evolutionary Genetics is supported by Institut Pasteur, Collège de France, the Centre national de la recherche scientifique, Fondation Allianz-Institut de France, the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID) and 'Milieu Intérieur' (ANR-10-LABX-69-01), Fondation de France (grant no. 00106080), and Fondation pour la Recherche Médicale (Equipe FRM DEQ20180339214). The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH, R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, the NIH Clinical and Translational Science Award program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics, and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (UM1HG006504 and U24HG008956), the Yale High-Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM, EQU201903007798), the FRM and ANR GENCOVID project, the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, INSERM, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), and the University of Paris. P. Bastard was supported by the FRM (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt-Schueller). The National Laboratory of Genomics for Biodiversity (LANGEBIO-CINVESTAV) in Mexico is supported by Consejo Nacional de Ciencia y Technologia (grant number FONCICYT/50/2016), The Newton Fund through the Medical Research Council (grant number MR/N028937/1), and the International Center for Genetic Engineering and Biotechnology grant number CRP/MEX20-01, awarded to A. Moreno-Estrada. S.G. Tangye is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia (1176665) and the Jeffrey Modell Foundation. Clinical Immunogenomics Research Consortium Australasia investigators (K.-C. Hsiao, P. McNaughton, A. Blincoe, J. Peake, S.G. Tangye, and P. Gray) are supported by the John Brown Cook Foundation. This work was supported by the National Institutes of Health grants R01-HL093093 (S.T. McGarvey) and R01-HL133040 (R.L. Minster). Molecular data for the Trans-Omics in Precision Medicine (TOPMed) program were provided by the National Heart, Lung, and Blood Institute (NHLBI). Genome sequencing for the Soifua Manuia study, labeled 'NHLBI TOPMed: Genome-wide Association Study of Adiposity in Samoans' (phs000972.v4.p1) in the dbGaP, was performed at the Northwest Genomics Center (HHSN268201100037C) and the New York Genome Center (HHSN268201500016C). Core support, including centralized genomic read mapping and genotype calling, along with variant quality metrics and filtering, was provided by the TOPMed Informatics Research Center (3R01-HL117626-02S1, contract HHSN268201800002I). Core support, including phenotype harmonization, data management, sample-identity QC, and general program coordination, was also provided by the TOPMed Data Coordinating Center (R01-HL120393, U01-HL120393, contract HHSN268201800001I). We gratefully acknowledge the studies and participants who provided biological samples and data for TOPMed. This research was funded in whole or in part by the French National Research Agency (ANR)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Institut Pasteur [Paris]-Université Paris Cité (UPC), University of Oxford [Oxford], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institute for Regenerative Medicine and Biotherapy [Montpellier], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Université Paris Cité (UPC), Garvan Institute of Medical Research [Sydney, Australia], and Chaire Génomique humaine et évolution
- Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics ,Infectious disease and host defense ,Homozygote ,Immunology ,Innate immunity and inflammation ,Receptor, Interferon alpha-beta ,Polynesia ,Virus Diseases ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Humans ,Immunology and Allergy ,Immunodeficiency ,Child ,Alleles ,Human disease genetics - Abstract
International audience; Globally, autosomal recessive IFNAR1 deficiency is a rare inborn error of immunity underlying susceptibility to live attenuated vaccine and wild-type viruses. We report seven children from five unrelated kindreds of western Polynesian ancestry who suffered from severe viral diseases. All the patients are homozygous for the same nonsense IFNAR1 variant (p.Glu386*). This allele encodes a truncated protein that is absent from the cell surface and is loss-of-function. The fibroblasts of the patients do not respond to type I IFNs (IFN-α2, IFN-ω, or IFN-β). Remarkably, this IFNAR1 variant has a minor allele frequency >1% in Samoa and is also observed in the Cook, Society, Marquesas, and Austral islands, as well as Fiji, whereas it is extremely rare or absent in the other populations tested, including those of the Pacific region. Inherited IFNAR1 deficiency should be considered in individuals of Polynesian ancestry with severe viral illnesses.
- Published
- 2022
43. Spatial dependence between training and test sets: another pitfall of classification accuracy assessment in remote sensing
- Author
-
N. Karasiak, Claude Monteil, Jean-François Dejoux, David Sheeren, Dynamiques et écologie des paysages agriforestiers (DYNAFOR), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'études spatiales de la biosphère (CESBIO), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), and French Ministry of Higher Education and Research (University of Toulouse)
- Subjects
Contextual image classification ,Pixel ,Property (programming) ,Computer science ,Overfitting ,Cross-validation ,02 engineering and technology ,Remote sensing ,Python (programming language) ,Accuracy assessment ,Artificial Intelligence ,Sample size determination ,020204 information systems ,0202 electrical engineering, electronic engineering, information engineering ,[INFO]Computer Science [cs] ,020201 artificial intelligence & image processing ,Spatial dependence ,computer ,Spatial analysis ,Spatial autocorrelation ,Software ,Independence (probability theory) ,computer.programming_language - Abstract
International audience; Spatial autocorrelation is inherent to remotely sensed data. Nearby pixels are more similar than distant ones. This property can help to improve the classification performance, by adding spatial or contextual features into the model. However, it can also lead to overestimation of generalisation capabilities, if the spatial dependence between training and test sets is ignored. In this paper, we review existing approaches that deal with spatial autocorrelation for image classification in remote sensing and demonstrate the importance of bias in accuracy metrics when spatial independence between the training and test sets is not respected. We compare three spatial and non-spatial cross-validation strategies at pixel and object levels and study how performances vary at different sample sizes. Experiments based on Sentinel-2 data for mapping two simple forest classes show that spatial leave-one-out cross-validation is the better strategy to provide unbiased estimates of predictive error. Its performance metrics are consistent with the real quality of the resulting map contrary to traditional non-spatial cross-validation that overestimates accuracy. This highlight the need to change practices in classification accuracy assessment. To encourage it we developped Museo ToolBox, an open-source python library that makes spatial cross-validation possible.
- Published
- 2021
44. Sex Differences in the Evolution of Neutralizing Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2
- Author
-
Cyril Planchais, David Rey, Aurélie Velay, Ludivine Grzelak, Yoann Madec, Yves Hansmann, Isabelle Staropoli, Marie-Josée Wendling, Samira Fafi-Kremer, Arnaud Fontanet, Catherine Schmidt-Mutter, Timothée Bruel, Hugo Mouquet, Nathalie Reix, Ludovic Glady, Floriane Gallais, Olivier Schwartz, María González, Nicolas Meyer, Jérôme De Seze, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), 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), 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]-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), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Strasbourg, Groupe Méthodes en Recherche Clinique [Strasbourg] (GMRC), Nouvel Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), S. F. K.’s laboratory is funded by Strasbourg University Hospitals (Hôpitaux Universitaires de Strasbourg, PRI 7782), Agence Nationale de la Recherche (ANR-18-CE17-0028), Laboratoire d’Excellence TRANSPLANTEX (ANR-11-LABX-0070_TRANSPLANTEX), and Institut National de la Santé et de la Recherche Médicale (UMR_S 1109). O. S.’s laboratory is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Agence Nationale de recherches sur le sida, Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), 'TIMTAMDEN' Agence Nationale de la Recherche ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01, the Gilead HIV cure program, and ANR/Fondation Pour la Recherche Médicale Flash COVID. L. Gr., is supported by the French Ministry of Higher Education, Research and Innovation., ANR-18-CE17-0028,HuMABK,Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées(2018), ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute [Créteil, France] (VRI), univOAK, Archive ouverte, APPEL À PROJETS GÉNÉRIQUE 2018 - Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées - - HuMABK2018 - ANR-18-CE17-0028 - AAPG2018 - VALID, Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app - - TRANSPLANTEX2011 - ANR-11-LABX-0070 - LABX - VALID, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Appel à projets générique - Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue - - TIMTAMDEN2014 - ANR-14-CE14-0029 - Appel à projets générique - VALID, and Appel à projets générique - Multiplication et Relation avec l'hôte du virus Chikungunya - - CHIKV-Viro-Immuno2014 - ANR-14-CE14-0015 - Appel à projets générique - VALID
- Subjects
0301 basic medicine ,sex-related differences ,MESH: Spike Glycoprotein, Coronavirus ,medicine.disease_cause ,Immunoglobulin G ,MESH: Antibodies, Neutralizing ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,antibodies ,MESH: COVID-19 ,Immunology and Allergy ,Medicine ,MESH: SARS-CoV-2 ,030212 general & internal medicine ,Polymerase chain reaction ,Coronavirus ,MESH: Immunoglobulin G ,2. Zero hunger ,MESH: Humans ,MESH: Middle Aged ,biology ,SARS-CoV-2 ,business.industry ,COVID-19 ,MESH: Adult ,MESH: Immunoglobulin M ,MESH: Male ,3. Good health ,030104 developmental biology ,Infectious Diseases ,Real-time polymerase chain reaction ,[INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV] ,Immunoglobulin M ,MESH: HEK293 Cells ,[INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV] ,Immunology ,biology.protein ,MESH: Health Personnel ,Antibody ,business ,MESH: Female ,Body mass index ,MESH: Antibodies, Viral ,MESH: Sex Characteristics ,Sex characteristics - Abstract
We measured anti-spike (S), nucleoprotein (N), and neutralizing antibodies in sera from 308 healthcare workers with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 and with mild disease, collected at 2 timepoints up to 6 months after symptom onset. At month 1, anti-S and -N antibody levels were higher in male participants aged >50 years and participants with a body mass index (BMI) >25 kg/m2. At months 3–6, anti-S and anti-N antibodies were detected in 99% and 59% of individuals, respectively. Anti-S antibodies and neutralizing antibodies declined faster in men than in women, independent of age and BMI, suggesting an association of sex with evolution of the humoral response.
- Published
- 2021
45. Foraminifera and plastic pollution: Knowledge gaps and research opportunities
- Author
-
Vincent M.P. Bouchet, Laurent Seuront, Akira Tsujimoto, Julien Richirt, Fabrizio Frontalini, Masashi Tsuchiya, Misako Matsuba, Hidetaka Nomaki, Laboratoire d’Océanologie et de Géosciences (LOG) - UMR 8187 (LOG), Institut national des sciences de l'Univers (INSU - CNRS)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Nord]), Shimane University, Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Università degli Studi di Urbino 'Carlo Bo', and Pierre-Hubert Curien Sakura program (project number: 47041NL), implemented by the French Ministry for Europe and Foreign Affairs, the French Ministry of Higher Education, Research and Innovation and the Japan Society for the Promotion of Science (JPJSBP 120213211).
- Subjects
emerging pollutants ,coastal habitats ,biology ,ecosystem functioning ,Health, Toxicology and Mutagenesis ,[SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology ,General Medicine ,ecology ,[SDE.BE]Environmental Sciences/Biodiversity and Ecology ,Toxicology ,Pollution - Abstract
International audience; Plastic has become one of the most ubiquitous and environmentally threatening sources of pollution in the Anthropocene. Beyond the conspicuous visual impact and physical damages, plastics both carry and release a cocktail of harmful chemicals, such as monomers, additives and persistent organic pollutants. Here we show through a review of the scientific literature dealing with both plastic pollution and benthic foraminifera (Rhizaria), that despite their critical roles in the structure and function of benthic ecosystems, only 0.4% of studies have investigated the effects of micro-and nano-plastics on this group. Consequently, we urge to consider benthic foraminifera in plastic pollution studies via a tentative roadmap that includes (i) the use of their biological, physiological and behavioral responses that may unveil the effects of microplastics and nanoplastics and (ii) the evaluation of the indicative value of foraminiferal species to serve as proxies for the degree of pollution. This appears particularly timely in the context of the development of management strategies to restore coastal ecosystems.
- Published
- 2023
46. Polymer-Based Nanostructures for Pancreatic Beta-Cell Imaging and Non-Invasive Treatment of Diabetes
- Author
-
Shakila Behzadifar, Alexandre Barras, Valérie Plaisance, Valérie Pawlowski, Sabine Szunerits, Amar Abderrahmani, Rabah Boukherroub, NanoBioInterfaces - IEMN (NBI - IEMN), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), The CNRS, the University of Lille, the Hauts-de-France region, and the Agence Nationale de la Recherche (project: NANOMIC) are acknowledged for financial support., The doctorate of S.B. is financed by the French Ministry of Higher Education, Research, and Innovation (MESRI)., and ANR-22-CE09-0016,NANOMIC,NANO plateforme innovant transportant des nanobodies et du manganèse pour le traçage et l'imagerie spécifique par résonance magnétique des cellules béta pancréatiques(2022)
- Subjects
polymer-based nanostructures ,antidiabetic drug delivery ,[CHIM.POLY]Chemical Sciences/Polymers ,[SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology ,diabetes ,foot ulcers ,beta cells mass ,imaging ,Pharmaceutical Science - Abstract
International audience; Diabetes poses major economic, social, and public health challenges in all countries worldwide. Besides cardiovascular disease and microangiopathy, diabetes is a leading cause of foot ulcers and lower limb amputations. With the continued rise of diabetes prevalence, it is expected that the future burden of diabetes complications, early mortality, and disabilities will increase. The diabetes epidemic is partly caused by the current lack of clinical imaging diagnostic tools, the timely monitoring of insulin secretion and insulin-expressing cell mass (beta (β)-cells), and the lack of patients’ adherence to treatment, because some drugs are not tolerated or invasively administrated. In addition to this, there is a lack of efficient topical treatment capable of stopping the progression of disabilities, in particular for treating foot ulcers. In this context, polymer-based nanostructures garnered significant interest due to their tunable physicochemical characteristics, rich diversity, and biocompatibility. This review article emphasizes the last advances and discusses the prospects in the use of polymeric materials as nanocarriers for β-cell imaging and non-invasive drug delivery of insulin and antidiabetic drugs in the management of blood glucose and foot ulcers.
- Published
- 2023
47. The anti-immune dengue subgenomic flaviviral RNA is present in vesicles in mosquito saliva and is associated with increased infectivity
- Author
-
Yeh, Shih-Chia, Strilets, Tania, Tan, Wei-Lian, Castillo, David, Medkour, Hacene, Rey-Cadilhac, Félix, Serrato-Pomar, Idalba, Rachenne, Florian, Chowdhury, Avisha, Chuo, Vanessa, Azar, Sasha, Singh, Moirangthem Kiran, Hamel, Rodolphe, Missé, Dorothée, Kini, R, Kenney, Linda, Vasilakis, Nikos, Marti-Renom, Marc a, Nir, Guy, Pompon, Julien, Garcia-Blanco, Mariano, Duke-NUS Medical School [Singapore], The University of Texas Medical Branch (UTMB), Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), National University of Singapore (NUS), Department of Computer and Information Science [Pennsylvania] (CIS), University of Pennsylvania, Barcelona Institute of Science and Technology (BIST), Universitat Pompeu Fabra [Barcelona] (UPF), ICREA Infection Biology Laboratory (Department of Experimental and Health Sciences), University of Texas Medical Branch at Galveston, Support for this research came from a fellowship from the McLauglin Family Foundation to TS, scholarships from the Fondation pour la Recherche Médicale (FRM project SPF202110013925) to HM, from the Institut Méditerranéen Hospitalier (IHU, Marseille) to IMSP and from the graduate school French Ministry of Higher Education and Research to FRC and FR, UTMB start-up funds and Cancer Prevention & Research Institute of Texas grant RP200650 to LJK and MKS, the Ministerio de Ciencia e Innovación (PID2020-115696RB-I00) to MAM-R, Cancer Prevention & Research Institute of Texas grant ID RR210018 to GN, Ministry of Education (Singapore) Tier3 grant (MOE2015-T3-1-003) to RMK and JP, a National Medical Research Council (Singapore) ZRRF grant (ZRRF/007/2017) to JP, a French Agence Nationale de la Recherche grant (ANR-20-CE15-0006) to JP, and the Duke-NUS Signature Research Programme funded by the Agency for Science Technology and Research (A*Star Singapore) and NIH/NIAID P01 AI150585 to MAGB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., and ANR-20-CE15-0006,VirSalivaEnhancer,Amplificateur de transmission d'origine flavivirale dans la salive de moustique(2020)
- Subjects
3' UTR ,Immunology ,MESH: Dengue ,Transfection ,Mosquitoes ,Microbiology ,Dengue virus ,Guide RNA ,Ribonucleases ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Virology ,Genetics ,MESH: Flavivirus ,MESH: Animals ,MESH: Saliva ,Saliva ,Molecular Biology ,MESH: Humans ,MESH: Subgenomic RNA ,MESH: Virus Replication ,MESH: Aedes ,MESH: 3' Untranslated Regions ,RNA extraction ,MESH: RNA, Viral ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Parasitology ,MESH: Culicidae - Abstract
Mosquito transmission of dengue viruses to humans starts with infection of skin resident cells at the biting site. There is great interest in identifying transmission-enhancing factors in mosquito saliva in order to counteract them. Here we report the discovery of high levels of the anti-immune subgenomic flaviviral RNA (sfRNA) in dengue virus 2-infected mosquito saliva. We established that sfRNA is present in saliva using three different methods: northern blot, RT-qPCR and RNA sequencing. We next show that salivary sfRNA is protected in detergent-sensitive compartments, likely extracellular vesicles. In support of this hypothesis, we visualized viral RNAs in vesicles in mosquito saliva and noted a marked enrichment of signal from 3'UTR sequences, which is consistent with the presence of sfRNA. Furthermore, we show that incubation with mosquito saliva containing higher sfRNA levels results in higher virus infectivity in a human hepatoma cell line and human primary dermal fibroblasts. Transfection of 3'UTR RNA prior to DENV2 infection inhibited type I and III interferon induction and signaling, and enhanced viral replication. Therefore, we posit that sfRNA present in salivary extracellular vesicles is delivered to cells at the biting site to inhibit innate immunity and enhance dengue virus transmission. Support for this research came from a fellowship from the McLauglin Family Foundation to TS, scholarships from the Fondation pour la Recherche Médicale (FRM project SPF202110013925) to HM, from the Institut Méditerranéen Hospitalier (IHU, Marseille) to IMSP and from the graduate school French Ministry of Higher Education and Research to FRC and FR, UTMB start-up funds and Cancer Prevention & Research Institute of Texas grant RP200650 to LJK and MKS, the Ministerio de Ciencia e Innovación (PID2020-115696RB-I00) to MAM-R, Cancer Prevention & Research Institute of Texas grant ID RR210018 to GN, Ministry of Education (Singapore) Tier3 grant (MOE2015-T3-1-003) to RMK and JP, a National Medical Research Council (Singapore) ZRRF grant (ZRRF/007/2017) to JP, a French Agence Nationale de la Recherche grant (ANR-20-CE15-0006) to JP, and the Duke-NUS Signature Research Programme funded by the Agency for Science Technology and Research (A*Star Singapore) and NIH/NIAID P01 AI150585 to MAGB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Published
- 2023
48. Paternalistic Countryside : the Hard Way towards Local Development in the Rural Municipalities of Central Hungary
- Author
-
Samuel Depraz, Environnement Ville Société (EVS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École nationale supérieure d'architecture de Lyon (ENSAL)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Nationale des Travaux Publics de l'État (ENTPE)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), French Ministry for Higher Education and Research / Laboratory MTE / UMR 5045 CNRS, Montpellier. Material support was kindly given by the Alföld Institute of the Centre for Regional Studies of the Hungarian Academy of Sciences directed by Pr. Bálint CSATÁRI., Program of the French Ministry for Higher Education and Research, ACI 'Espace et territoires', lead in by Pr. Marie-Claude MAUREL (EHESS, Paris), Environnement Ville Société ( EVS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -Université Jean Moulin - Lyon III-Université Jean Monnet [Saint-Étienne] ( UJM ) -École Nationale des Travaux Publics de l'État ( ENTPE ) -Ecole Nationale Supérieure des Mines de Saint-Etienne-École nationale supérieure d'architecture de Lyon ( ENSAL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ), Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Hungary ,Local Development ,Rural Élite ,[SHS.GEO]Humanities and Social Sciences/Geography ,Municipal Policies ,[ SHS.GEO ] Humanities and Social Sciences/Geography - Abstract
This paper is an improved and enlarged version of DEPRAZ S. (2005), « Développement local et politiques de gestion des communes rurales en Hongrie post-socialiste », in Bulletin de l’Association de géographes français, vol. 82 n°2 : « Les territoires ruraux centre-européens face aux enjeux de l’intégration », p. 168-181 : halshs-01547048v1 / DOI : ; International audience; The new political and budgetary standards for Hungarian local governments, introduced as early as 1990 in accordance with the criteria of the European integration, aimed at promoting local democracy and reinforced the autonomy of local governments. Furthermore, they were supposed to stimulate development on the short term, so that local societies would show initiative through co-operation and a fair territorial competition.The results of this policy seem nevertheless to remain beyond expectations, at least in rural areas of the Hungarian Great Plain. Rural poverty, together with an unfavourable settlement structure, are often seen as the main causes of this miscarriage. But a somewhat grudging local budgetary policy and, which is more, a strong stability of local representatives inherited from a conservative social hierarchy make Hungarian local societies quite unable to run efficiently endogenous development policies. Thus the legacy of the socialist era does not seem to be the perpetuation of the values of the former system, but rather the reinforcement of a long-lasting paternalistic social structure of the countryside.
- Published
- 2006
49. Topological Analysis of Hydroxyquinoline Derivatives Interacting with Aluminum Cations or with an Al(111) Surface
- Author
-
Corinne Lacaze-Dufaure, Christine Lepetit, Yann Bulteau, Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), 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 Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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 Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and French Ministry of Higher Education and Research
- Subjects
Anions ,Matériaux ,Substituent ,Reaction products ,Ionic bonding ,02 engineering and technology ,010402 general chemistry ,Topology ,01 natural sciences ,[SPI.MAT]Engineering Sciences [physics]/Materials ,Inorganic Chemistry ,Aluminum Cation ,chemistry.chemical_compound ,Deprotonation ,Adsorption ,Molecule ,Moiety ,Physical and Theoretical Chemistry ,Molecules ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,chemistry ,Density functional theory ,0210 nano-technology ,Aluminum - Abstract
International audience; The reactivity of hydroxyquinoline derivatives (native molecules (Hq) and modified species (HqX, X = Br, SO3H, or SO3–)) is investigated either (i) with aluminum cations for the formation of chelates or (ii) with aluminum surfaces for their adsorption properties, in the framework of the dispersion-corrected Density Functional Theory (DFT-D). It is shown that the substituent X has no influence on the complexation to the aluminum cation of the deprotonated active form, i.e., the one exhibiting a phenolate moiety and referred to as q– for the native Hq and qXn– (n = 1 or 2) for its derivatives. The formation energies of the Alq3 and Al(qX)3 complexes, taking values of −60.87 ± 3.10 eV in vacuum and −24.30 ± 0.29 eV in water, are indicative of a strong chelating affinity of the q– and qXn– (n = 1 or 2) anions for the aluminum cations. ELF and QTAIM topological analyses on these complexes evidence that the bonding of the deprotonated species with the Al3+ ion is ionic with a very weak covalence degree. The para or ortho substituent X of the phenolate moiety of the qXn– (n = 1 or 2) derivatives modifies the electronic structure only locally and thus does not influence their O- or N-coordinating properties. The adsorption properties of the latter on an Al(111) surface have also been studied within periodic DFT-D calculations. The adsorbed species are strongly interacting with the Al(111) surface, as shown by the value of the adsorption energy of −3.69 ± 0.21 eV for the most stable geometries. Various adsorption modes of the q– and qXn– (n = 1 or 2) derivatives are characterized on the Al surface, depending on stabilizing or destabilizing interactions with the substituents X. On the basis of QTAIM descriptors, the bonding of the hydroxyquinoline species on the aluminum surface is characterized as ionic with a weak covalent character.
- Published
- 2020
50. Multi-Approach Analysis Reveals Local Adaptation in a Widespread Forest Tree of Reunion Island
- Author
-
Garot, Edith, Dussert, Stephane, Domergue, Frédéric, Joët, Thierry, Fock-Bastide, Isabelle, Combes, Marie-Christine, Lashermes, Philippe, Diversité, adaptation, développement des plantes (UMR DIADE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université de La Réunion (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), The European Union (European Regional Development Fund), Région Réunion, and the Institut de Recherche pour le Développement (IRD) (CAFEDIV project 'Caractérisation et valorisation d’une espèce endémique des forêts réunionnaises : le caféier marron' GURDTI/20171191-00002607). E.G. benefited a doctoral grant from the French Ministry of Higher Education, Research and Innovation (University of Montpellier)., and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
AcademicSubjects/SCI01210 ,Climate ,Leaf morphology ,Climate Change ,Regular Papers ,Coffea ,Genomics ,Forests ,AcademicSubjects/SCI01180 ,Adaptation, Physiological ,Polymorphism, Single Nucleotide ,Cuticular wax composition ,Trees ,Plant Leaves ,Quantitative Trait, Heritable ,Landscape genomics ,Gene expression ,[SDE.BE]Environmental Sciences/Biodiversity and Ecology ,Reunion ,Coffea mauritiana ,Genome-Wide Association Study - Abstract
Accession number: The nucleotide sequences reported in this article have been submitted to the European Nucleotide Archive under accession numbers SAMEA5423234 to SAMEA5423258 (study no PRJEB31715).The nucleotide sequences reported in this article have been submitted to the European Nucleotide Archive under accession numbers SAMEA5423234 to SAMEA5423258 (study no PRJEB31715); International audience; Detecting processes of local adaptation in forest trees andidentifying environmental selective drivers are of primaryimportance for forest management and conservation. Transplant experiments, functional genomics and population genomics are complementary tools to efficiently characterize heritable phenotypic traits and to decipher the genetic bases of adaptive traits. Using an integrative approach combining phenotypic assessment in common garden, transcriptomics and landscape genomics, we investigated leaf adaptive traits in Coffea mauritiana, a forest tree endemic to Reunion Island. Eight populations of C. mauritiana originating from sites with contrasted environmental conditions were sampled in common garden to assessseveral leaf morphological traits, to analyze the leaf transcriptome and leaf cuticular wax composition. The relative alkane content of cuticular waxes was significantly correlated with major climatic gradients, paving the way for further transcriptome-based analyses. The expression pattern of cuticle biosynthetic genes was consistent with a modulation of alkane accumulation across the population studied, supporting the hypothesis that the composition of cuticular wax is involved in the local adaptation of C. mauritiana. Association tests in landscape genomics performed using RNA-seq-derived single-nucleotide polymorphisms revealed that genes associated with cell wall remodeling also likely play an adaptive role. By combining these different approaches, this study efficiently identified local adaptation processes in a non-model species. Our results provide the first evidence for local adaptation in trees endemic to Reunion Island and highlight the importance of cuticle composition for the adaptation of trees to the high evaporative demand in warm climates.
- Published
- 2020
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.