Author: "European Project" / Topic: [sdv]life sciences [q-bio] - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"European Project"' showing total 3,167 results

Start Over Author "European Project" Topic [sdv]life sciences [q-bio]

3,167 results on '"European Project"'

1. The Expanding Menagerie of Prunus-Infecting Luteoviruses

Author: Maryam Khalili, Thierry Candresse, Igor Koloniuk, Dana Safarova, Yoann Brans, Chantal Faure, Marine Delmas, Sébastien Massart, Miguel A. Aranda, Kadriye Caglayan, Veronique Decroocq, Pavlina Drogoudi, Miroslav Glasa, George Pantelidis, Milan Navratil, François Latour, Josef Spak, Jaroslava Pribylova, Daniel Mihalik, Francesco Palmisano, Antonella Saponari, Tomas Necas, Jiri Sedlak, Armelle Marais, Biologie du fruit et pathologie (BFP), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute of Plant Molecular Biology, Biological Centre, Czech Academy of Sciences [Prague] (CAS), Palacky University Olomouc, Centre Technique Interprofessionnel des Fruits et Légumes (CTIFL), Unité Expérimentale Arboricole (UE ARBO), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), TERRA, Gembloux Agro-Bio Tech, Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Hatay Mustafa Kemal University, Ellinikos Georgikos OrGanismos-DIMITRA (ELGO -DIMITRA), Slovak Academy of Science [Bratislava] (SAS), Institute of Biology, Ss Cyril and Methodius University in Skopje, Agricultural Research and Experimentation Centre 'Basile Caramia', Mendel University in Brno (MENDELU), Vyzkumny A Slechtitelsky Ustav Ovocnarsky, This study was funded by the European Union through the Horizon 2020 Marie Skłodowska-Curie Actions Innovative Training Network (H2020 MSCA- 60 ITN) project 'INEXTVIR' (Grant agreement number 813542). The ChLVA research part was financed by Academy of Sciences of the Czech Republic support (RVO60077344). The plant indexing biological tests conducted by CTIFL were funded by INTERFEL (Fresh fruit and 68vegetable interprofessional association). D. Safarova and M. Navratil have received support from the Ministry of Agriculture of the Czech Republic, National Agency for Agricultural Research (Project no. QK1920124). M. Glasa and D. Mihálik have received support from the Slovak Research & Development Agency (project APVV-18-0005), European Project: H2020 MSCA-60 ITN, and European Project: 813542,INEXTVIR
Subjects: biological indexing, Stone fruit, [SDV]Life Sciences [q-bio], Luteovirus, geographical distribution, HTS, Plant Science, Pathogen Detection, Agronomy and Crop Science, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy
Abstract: International audience; Members of the genus Luteovirus are responsible for economically destructive plant diseases worldwide. Over the past few years, three luteoviruses infecting Prunus trees have been characterized. However, the biological properties, prevalence, and genetic diversity of those viruses have not yet been studied. High throughput sequencing of samples of various wild, cultivated, and ornamental Prunus species enabled the identification of four novel species in the genus Luteovirus for which we obtained complete or nearly complete genomes. Besides, we identified another new putative species recovered from Sequence Read Archive data. Furthermore, we conducted a survey on peach-infecting luteoviruses in eight European countries. Analyses of 350 leaf samples collected from germplasm, production orchards, and private gardens showed that peach-associated luteovirus (PaLV), nectarine stem pitting-associated virus (NSPaV), and a novel luteovirus, peach-associated luteovirus 2 (PaLV2), are present in all countries, while the most prevalent virus was NSPaV, followed by PaLV. An analysis of the genetic diversity of these viruses was also conducted. Moreover, the biological indexing on GF305 peach indicator plants demonstrated that PaLV and PaLV2, like NSPaV, are transmitted by graft at relatively low rates. No clear viral symptoms have been observed either in graft-inoculated GF305 indicators, or in different peach tree varieties observed in an orchard. The data generated during this study provide a broader overview of the genetic diversity, geographical distribution and prevalence of peach-infecting luteoviruses, and suggest these viruses are likely asymptomatic in peach under most circumstances.
Published: 2023
Full Text: View/download PDF

2. High-resolution synchrotron K-edge subtraction CT allows tracking and quantifying therapeutic cells and their scaffold in a rat model of focal cerebral injury and can serve as a reference for spectral photon counting CT

Author: Clément Tavakoli, Elisa Cuccione, Chloé Dumot, Joëlle Balegamire, Salim Aymeric Si-Mohamed, Johoon Kim, Claire Crola-da-Silva, Yves Chevalier, Loïc Boussel, Philippe Douek, David Cormode, Hélène Elleaume, Emmanuel Brun, Marlène Wiart, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Hospices Civils de Lyon (HCL), Laboratoire d'automatique, de génie des procédés et de génie pharmaceutique (LAGEPP), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Pradel [CHU - HCL], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, ANR-18-CE19-0003,BREAKTHRU,Développement de l'imagerie bicolore à l'aide d'un scanner X spectral à comptage de photons pour l'évaluation in-vivo de thérapies cellulaires(2018), European Project: ESRF, European Project: 643694,SPCCT, Wiart, Marlene, APPEL À PROJETS GÉNÉRIQUE 2018 - Développement de l'imagerie bicolore à l'aide d'un scanner X spectral à comptage de photons pour l'évaluation in-vivo de thérapies cellulaires - - BREAKTHRU2018 - ANR-18-CE19-0003 - AAPG2018 - VALID, MD1094 - ESRF - INCOMING, H2020 - SPCCT - 643694 - INCOMING, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV] Life Sciences [q-bio], Synchrotron K-edge subtraction CT, [SPI]Engineering Sciences [physics], cell tracking, [SPI] Engineering Sciences [physics], neurology, [SDV]Life Sciences [q-bio], spectral photon-counting CT, Biomedical Engineering, regenerative medicine, Medicine (miscellaneous), Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Biotechnology
Abstract: International audience; Background: The objective of this study was to demonstrate that synchrotron K-edge subtraction tomography (SKES-CT) can simultaneously track therapeutic cells and their encapsulating carrier, in vivo, in a rat model of focal brain injury using a dual-contrast agent approach. The second objective was to determine if SKES-CT could be used as a reference method for spectral photon counting tomography (SPCCT). Methods: Phantoms containing different concentrations of gold and iodine nanoparticles (AuNPS/INPs) were imaged with SKES-CT and SPCCT to assess their performances. A pre-clinical study was performed in rats with focal cerebral injury which intracerebrally received AuNPs-labelled therapeutic cells encapsulated in a INPs-labelled scaffold. Animals were imaged in vivo with SKES-CT and back-to-back with SPCCT. Results: SKES-CT revealed to be reliable for quantification of gold and iodine, whether alone or mixed. In the preclinical model, SKES-CT showed that AuNPs remained at the site of cell injection, while INPs expanded within and/or along the lesion border, suggesting dissociation of both components in the first days post-administration. Compared to SKES-CT, SPCCT was able to correctly locate gold, but not completely located iodine. When SKES-CT was used as reference, SPCCT gold quantification appeared very accurate both in vitro and in vivo. Iodine quantification by SPCCT was also quite accurate, albeit less so than for gold. Conclusion: We here provide the proof-of-concept that SKES-CT is a novel method of choice for performing dual-contrast agent imaging in the context of brain regenerative therapy. SKES-CT may also serve as ground truth for emerging technologies such as multicolour clinical SPCCT.
Published: 2023
Full Text: View/download PDF

3. Steering self-organisation through confinement

Author: Araújo, Nuno A.M., Janssen, Liesbeth M.C., Barois, Thomas, Boffetta, Guido, Cohen, Itai, Corbetta, Alessandro, Dauchot, Olivier, Dijkstra, Marjolein, Durham, William M., Dussutour, Audrey, Garnier, Simon, Gelderblom, Hanneke, Golestanian, Ramin, Isa, Lucio, Koenderink, Gijsje H., Löwen, Hartmut, Metzler, Ralf, Polin, Marco, Royall, C. Patrick, Šarić, Anđela, Sengupta, Anupam, Sykes, Cécile, Trianni, Vito, Tuval, Idan, Vogel, Nicolas, Yeomans, Julia M., Zuriguel, Iker, Marin, Alvaro, Volpe, Giorgio, Sub Soft Condensed Matter, Soft Condensed Matter and Biophysics, Sub Soft Condensed Matter, Soft Condensed Matter and Biophysics, MESA+ Institute, Physics of Fluids, Universidade de Lisboa, Eindhoven University of Technology [Eindhoven] (TU/e), Laboratoire Ondes et Matière d'Aquitaine (LOMA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Torino = University of Turin (UNITO), Cornell University [New York], Laboratory of Atomic and Solid State Physics [Ithaca] (LASSP), Gulliver (UMR 7083), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Utrecht University [Utrecht], University of Sheffield [Sheffield], Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), New Jersey Institute of Technology [Newark] (NJIT), Max Planck Institute for Dynamics and Self-Organization (MPIDS), Max-Planck-Gesellschaft, Rudolf Peierls Centre for Theoretical Physics, University of Oxford, Department of Materials [ETH Zürich] (D-MATL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Kavli Institute of Nanosciences [Delft] (KI-NANO), Delft University of Technology (TU Delft), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University of Potsdam = Universität Potsdam, Institut Mediterrani d'Estudis Avancats (IMEDEA), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad de las Islas Baleares (UIB), Institute of Science and Technology [Klosterneuburg, Austria] (IST Austria), University of Luxembourg [Luxembourg], Matière Cellulaire Active, Laboratoire de physique de l'ENS - ENS Paris (LPENS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institute of Cognitive Sciences and Technologies, National Research Council of Italy (CNR) (ISTC), Universidad de Navarra [Pamplona] (UNAV), University of Twente, Department of Chemistry [University College of London], University College of London [London] (UCL), ANR-18-CE33-0006,MSR,Machines Morpho-fonctionelles en Essaim(2018), ANR-14-CE09-0006,Actin2Nucleus,Connexion mécanique entre le cytosquelette d'actine et le noyau(2014), ANR-12-BSV5-0014,Contract,Nouveaux systèmes biomimétiques pour étudier la contractilité acto-myosine cellulaire(2012), European Project: 884902,SoftML, European Project: 802960,NEPA, European Project: 955910,PHYMOT, and European Project: 678573,H2020,ERC-2015-STG,NanoPacks(2016)
Subjects: Pattern-formation, Physics - Physics and Society, Chemistry(all), [SDV]Life Sciences [q-bio], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Collective behavior, FOS: Physical sciences, Physics and Society (physics.soc-ph), General Chemistry, Condensed Matter - Soft Condensed Matter, Condensed Matter Physics, Nonlinear Sciences - Adaptation and Self-Organizing Systems, Particles, Biological Physics (physics.bio-ph), Information, Soft Condensed Matter (cond-mat.soft), Physics - Biological Physics, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], Adaptation and Self-Organizing Systems (nlin.AO)
Abstract: Self-organisation is the spontaneous emergence of spatio-temporal structures and patterns from the interaction of smaller individual units. Examples are found across many scales in very different systems and scientific disciplines, from physics, materials science and robotics to biology, geophysics andastronomy. Recent research has highlighted how self-organisation can be both mediated and controlled by confinement. Confinement is an action over a system that limits its units’ translational and rotational degrees of freedom, thus also influencing the system’s phase space probability density; it can functionas either a catalyst or inhibitor of self-organisation. Confinement can then become a means to actively steer the emergence or suppression of collective phenomena in space and time. Here, to provide a common framework and perspective for future research, we examine the role of confinement in the self-organisation of soft-matter systems and identify overarching scientific challenges that need to be addressed to harness its full scientific and technological potential in soft matter and related fields.By drawing analogies with other disciplines, this framework will accelerate a common deeper understanding of self-organisation and trigger the development of innovative strategies to steer it using confinement, with impact on, e.g., the design of smarter materials, tissue engineering for biomedicineand in guiding active matter.
Published: 2023
Full Text: View/download PDF

4. Associations of childhood adiposity with adult intima–media thickness and inflammation: a 20-year longitudinal population-based cohort

Author: Fujikawa, Tomona, Kobayashi, Masatake, Wagner, Sandra, Duarte, Kevin, Scherdel, Pauline, Heude, Barbara, Dupont, Vincent, Bozec, Erwan, Bresso, Emmanuel, Zannad, Faiez, Rossignol, Patrick, Girerd, Nicolas, 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), 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 ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), 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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153), 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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Centre Hospitalier Universitaire de Reims (CHU Reims), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), European Project, European Project: 305507,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HOMAGE(2013), and European Project: ERA-CVD/0001/2016,MINOTAUR
Subjects: inflammation, Physiology, [SDV]Life Sciences [q-bio], childhood adiposity, Internal Medicine, biomarkers, Cardiology and Cardiovascular Medicine, carotid intima–media thickness
Abstract: International audience; Background: The associations between childhood adiposity and adult increased carotid intima-media thickness (cIMT) have been well established, which might be corroborated by the association between adiposity in children and inflammation in adults. However, longitudinal data regarding biological pathways associated with childhood adiposity are lacking.Methods: The current study included participants from the STANISLAS cohort who had adiposity measurements at age 5-18 years [ N = 519, mean (SD) age, 13.0 (2.9) years; 46.4% male], and who were measured with cIMT, vascular-related and metabolic-related proteins at a median follow-up of 19 ± 2 years. BMI, waist-to-height ratio and waist circumference were converted to age-specific and sex-specific z -scores.Results: A minority of children were overweight/obese (16.2% overweight-BMI z -score >1; 1.3% obesity- z -score >2). Higher BMI, waist-height ratio and waist circumference in children were significantly associated with greater adult cIMT in univariable analysis, although not after adjusting for C-reactive protein. These associations were more pronounced in those with consistently high adiposity status from childhood to middle adulthood. Participants with higher adiposity during childhood (BMI or waist-height ratio) had higher levels of insulin-like growth factor-binding protein-1, protein-2, matrix metalloproteinase-3, osteopontin, hemoglobin and C-reactive protein in adulthood. Network analysis showed that IL-6, insulin-like growth factor-1 and fibronectin were the key proteins associated with childhood adiposity.Conclusion: In a population-based cohort followed for 20 years, higher BMI or waist-to-height ratio in childhood was significantly associated with greater cIMT and enhanced levels of proteins reflective of inflammation, supporting the importance of inflammation as progressive atherosclerosis in childhood adiposity.
Published: 2022
Full Text: View/download PDF

5. Avdoralimab (Anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FOR COVID Elimination [FORCE])*

Author: Julien, Carvelli, Ferhat, Meziani, Jean, Dellamonica, Pierre-Yves, Cordier, Jerome, Allardet-Servent, Megan, Fraisse, Lionel, Velly, Saber Davide, Barbar, Samuel, Lehingue, Christophe, Guervilly, Maxime, Desgrouas, Fabrice, Camou, Christelle, Piperoglou, Frederic, Vely, Olivier, Demaria, Joyson, Karakunnel, Joanna, Fares, Luciana, Batista, Federico, Rotolo, Julien, Viotti, Agnes, Boyer-Chammard, Karine, Lacombe, Erwan, Le Dault, Michel, Carles, Nicolas, Schleinitz, Eric, Vivier, Sarah, Djabarouti, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nouvel Hôpital Civil de Strasbourg, CHU Nice, Hopital l'Archet 1, Centre Hospitalier Universitaire de Nice (CHU Nice), Réanimation Polyvalente, HIA Laveran - Department of Intensive Care - Marseille, Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Hospitalier Victor Dupouy, Aix Marseille Université (AMU), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Nîmes University Hospital, Department of Intensive Care, Hôpital Saint-Joseph [Marseille], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Saint-André, Université de Bordeaux (UB), Innate Pharma, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), HIA Laveran a Marseille, European Project: 694502,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,TILC(2017), and European Project: 875102,MInflaTILC
Subjects: Oxygen, sepsis, Treatment Outcome, SARS-CoV-2, inflammation, [SDV]Life Sciences [q-bio], Humans, COVID-19, complement, Antibodies, Monoclonal, Humanized, avdoralimab, Critical Care and Intensive Care Medicine
Abstract: International audience; OBJECTIVES: Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19. DESIGN: FOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study. SETTING: Twelve clinical sites in France (ICU and general hospitals). PATIENTS: Patients receiving greater than or equal to 5 L oxygen/min to maintain Spo 2 greater than 93% (World Health Organization scale ≥ 5). Patients received conventional oxygen therapy or high-flow oxygen (HFO)/noninvasive ventilation (NIV) in cohort 1; HFO, NIV, or invasive mechanical ventilation (IMV) in cohort 2; and IMV in cohort 3. INTERVENTIONS: Patients were randomly assigned, in a 1:1 ratio, to receive avdoralimab or placebo. The primary outcome was clinical status on the World Health Organization ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2. MEASUREMENTS AND MAIN RESULTS: We randomized 207 patients: 99 in cohort 1, 49 in cohort 2, and 59 in cohort 3. During hospitalization, 95% of patients received glucocorticoids. Avdoralimab did not improve World Health Organization clinical scale score on days 14 and 28 (between-group difference on day 28 of-0.26 (95% CI,-1.2 to 0.7; p = 0.7) in cohort 1 and-0.28 (95% CI,-1.8 to 1.2; p = 0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of-6.3 (95% CI,-13.2 to 0.7; p = 0.96) or secondary outcomes in any cohort. No subgroup of interest was identified. CONCLUSIONS: In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 and 28 (funded by Innate Pharma, ClinicalTrials.gov number, NCT04371367).
Published: 2022
Full Text: View/download PDF

6. Expanding evolutionary theories of ageing to better account for symbioses and interactions throughout the Web of Life

Author: Bapteste, Eric, Huneman, Philippe, Keller, Laurent, Teulière, Jérôme, Lopez, Philippe, Teeling, Emma, Lindner, Ariel, Baudisch, Annette, Ludington, William, Franceschi, Claudio, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), European Project: 741491 ,resiliANT, and European Project: 101043983,GBO-DO
Subjects: Evolutionary theory of ageing symbioses microbiomes networks pluralism units of selection, microbiomes, networks, [SDV]Life Sciences [q-bio], Evolutionary theory of ageing, pluralism, symbioses, units of selection
Abstract: How, when, and why organisms age are fascinating issues that can only be fully addressed by adopting an evolutionary perspective. Consistently, the main evolutionary theories of ageing, namely the Mutation Accumulation theory, the Antagonistic Pleiotropy theory, and the Disposable Soma theory, have formulated stimulating hypotheses that structure current debates on both the proximal and ultimate causes of organismal ageing. However, all these theories leave a common area of biology relatively under-explored. The Mutation Accumulation theory and the Antagonistic Pleiotropy theory were developed under the traditional framework of population genetics, and therefore are logically centred on the ageing of individuals within a population. The Disposable Soma theory, based on principles of optimising physiology, mainly explains ageing within a species. Consequently, current leading evolutionary theories of ageing do not explicitly model the countless interspecific and ecological interactions, such as symbioses and host-microbiomes associations, increasingly recognized to shape organismal evolution across the Web of Life. Moreover, the development of network modelling supporting a deeper understanding on the molecular interactions associated with ageing within and between organisms is also bringing forward new questions regarding how and why molecular pathways associated with ageing evolved. Here, we take an evolutionary perspective to examine the effects of organismal interactions on ageing across different levels of biological organisation, and consider the impact of surrounding and nested systems on organismal ageing. We also apply this perspective to suggest open issues with potential to expand the standard evolutionary theories of ageing.
Published: 2023
Full Text: View/download PDF

7. Managing the deluge of newly discovered plant viruses and viroids: an optimized scientific and regulatory framework for their characterization and risk analysis

Author: Nuria Fontdevila Pareta, Maryam Khalili, Ayoub Maachi, Mark Paul S. Rivarez, Johan Rollin, Ferran Salavert, Coline Temple, Miguel A. Aranda, Neil Boonham, Marleen Botermans, Thierry Candresse, Adrian Fox, Yolanda Hernando, Denis Kutnjak, Armelle Marais, Françoise Petter, Maja Ravnikar, Ilhem Selmi, Rachid Tahzima, Charlotte Trontin, Thierry Wetzel, Sebastien Massart, Gembloux Agro-Bio Tech [Gembloux], Université de Liège, Biologie du fruit et pathologie (BFP), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecophysiologie et Génomique Fonctionnelle de la Vigne (UMR EGFV), Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Abiopep S.L., National Institute of Biology [Ljubljana] (NIB), Caraga State University, DNAVision, Newcastle University [Newcastle], Spanish National Research Council (CSIC), Netherlands Institute for Vectors, Invasive Plants and Plant Health (NIVIP), European and Mediterranean Plant Protection Organization - Organisation Européenne et Méditerranéenne pour la Protection des Plantes (EPPO), Research Institute for Agricultural, Fisheries and Food (ILVO), Bioversity International [Montpellier], Bioversity International [Rome], Consultative Group on International Agricultural Research [CGIAR] (CGIAR)-Consultative Group on International Agricultural Research [CGIAR] (CGIAR), This work was supported by the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 773139 (VALITEST) and under the Marie Skłodowska-Curie grant agreement no. 813542 (INEXTVIR), by the CGIAR Genbank platform and by the Germplasm Health Unit (GHU) improvement initiative., European Project: 773139,VALITEST, and European Project: 813542,INEXTVIR
Subjects: Microbiology (medical), high throughput sequencing (HTS), regulatory agencies, biological characterization, [SDV]Life Sciences [q-bio], plant viruses and viroids, Pest Risk Analysis (PRA), plant health, virus disease, Microbiology, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy
Abstract: International audience; The advances in high-throughput sequencing (HTS) technologies and bioinformatic tools have provided new opportunities for virus and viroid discovery and diagnostics. Hence, new sequences of viral origin are being discovered and published at a previously unseen rate. Therefore, a collective effort was undertaken to write and propose a framework for prioritizing the biological characterization steps needed after discovering a new plant virus to evaluate its impact at different levels. Even though the proposed approach was widely used, a revision of these guidelines was prepared to consider virus discovery and characterization trends and integrate novel approaches and tools recently published or under development. This updated framework is more adapted to the current rate of virus discovery and provides an improved prioritization for filling knowledge and data gaps. It consists of four distinct steps adapted to include a multi-stakeholder feedback loop. Key improvements include better prioritization and organization of the various steps, earlier data sharing among researchers and involved stakeholders, public database screening, and exploitation of genomic information to predict biological properties.
Published: 2023
Full Text: View/download PDF

8. SGLT2i for evidence based cardiorenal protection in diabetic and non-diabetic chronic kidney disease: a comprehensive review by EURECA-m and ERBP working groups of ERA

Author: Mark, Patrick, Sarafidis, Pantelis, Ekart, Robert, Ferro, Charles, Balafa, Olga, Fernandez-Fernandez, Beatriz, Herrington, William, Rossignol, Patrick, del Vecchio, Lucia, Valdivielso, José M., Mallamaci, Francesca, Ortiz, Alberto, Nistor, Ionut, Cozzolino, Mario, University of Glasgow, Aristotle University of Thessaloniki, Hippokration Hospital, University medical centre Maribor (UKC Maribor), University Hospitals Birmingham [Birmingham, Royaume-Uni], University of Birmingham [Birmingham], University Hospital of Ioannina, Universidad Autónoma de Madrid (UAM), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Nuffield Department of Population Health [Oxford], University of Oxford, 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), 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 ), Hôpital Princesse Grace [Monaco], ASST Lecco, University of Lleida-IRBLLEIDA-PCiTA, Vascular and Renal Translational Research Group and UDETMA, IRBLleida, CNR-IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hpertension Unit, Reggio Calabria, Reggio Calabria c/o Ospedali Riuniti, University of Medicine and Pharmacy 'Grigore T.Popa' Iasi (UMF lasi), Università degli Studi di Milano = University of Milan (UNIMI), AO/BFF research is supported by FIS/Fondos FEDER (PI18/01366, PI19/00588, PI19/00815, PI21/00251, PI20/00744, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, Sociedad Madrileña de Nefrología (SOMANE), FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM. Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS2040 (RD21/0005/0001) funded by European Union – NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia(MRR) and SPACKDc PMP21/00109, FEDER funds., European Project, and European Project: RD21/0005/000
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; Chronic kidney disease (CKD) is a major public health issue affecting an estimated 850 million people globally. The leading causes of CKD is diabetes and hypertension, which together account for more than 50% of patients with end-stage kidney disease. Progressive CKD leads to the requirement for kidney replacement therapy with transplantation or dialysis. In addition, CKD, is a risk factor for premature cardiovascular disease, particularly from structural heart disease and heart failure (HF). Until 2015, the mainstay of treatment to slow progression of both diabetic and many non-diabetic kidney diseases was blood pressure control and renin-angiotensin system inhibition; however, neither angiotensin converting enzyme inhibitors (ACEIs) nor angiotensin receptor blockers (ARBs) reduced cardiovascular events and mortality in major trials in CKD. The emergence of cardiovascular and renal benefits observed with sodium-glucose cotransporter-2 inhibitors (SGLT2i) from clinical trials of their use as antihyperglycaemic agents has led to a revolution in cardiorenal protection for patients with diabetes. Subsequent clinical trials, notably DAPA-HF, EMPEROR, CREDENCE, DAPA-CKD and EMPA-KIDNEY have demonstrated their benefits in reducing risk of HF and progression to kidney failure in patients with HF and/or CKD. The cardiorenal benefits - on a relative scale - appear similar in patients with or without diabetes. Specialty societies’ guidelines are continually adapting as trial data emerges to support increasingly wide use of SGLT2i. This consensus paper from EURECA-m and ERBP highlights the latest evidence and summarises the guidelines for use of SGLT2i for cardiorenal protection focusing on benefits observed relevant to people with CKD.
Published: 2023
Full Text: View/download PDF

9. Metagenome-derived virus-microbe ratios across ecosystems

Author: Purificación López-García, Ana Gutiérrez-Preciado, Mart Krupovic, Maria Ciobanu, Philippe Deschamps, Ludwig Jardillier, Mario López-Pérez, Francisco Rodríguez-Valera, David Moreira, Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Virologie des archées - Archaeal Virology, 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), Universidad Miguel Hernández [Elche] (UMH), We acknowledge support from the Moore-Simons Project on the Origin of the Eukaryotic Cell through Grant GBMF9739 (PL-G) and the European Research Council Advanced Grants FP7 No. 322669 (PL-G) and H2020 No. 787904 (DM), European Project: 322669,EC:FP7:ERC,ERC-2012-ADG_20120314,PROTISTWORLD(2013), and European Project: 787904,PLAST-EVOL
Subjects: [SDV]Life Sciences [q-bio], viruses, Aquatic ecosystem, Zoology, Biology, Plankton, biology.organism_classification, Microbiology, Lytic cycle, Metagenomics, Lysogenic cycle, Microbial mat, Bacteria, Ecology, Evolution, Behavior and Systematics, Archaea
Abstract: It is generally assumed that viruses outnumber cells on Earth by at least tenfold. Virus-to-microbe ratios (VMR) are largely based on counts of fluorescently labelled virus-like particles. However, these exclude intracellular viruses and potentially include false positives (DNA-containing vesicles, gene-transfer agents, unspecifically stained inert particles). Here, we develop a metagenome-based VMR estimate (mVRM) that accounts for DNA viruses across all stages of their replication cycles (virion, intracellular lytic and lysogenic) by using normalised RPKM (reads per kilobase of gene sequence per million of mapped metagenome reads) counts of the major capsid protein (MCP) genes and cellular universal single-copy genes (USCGs) as proxies for virus and cell counts, respectively. After benchmarking this strategy using mock metagenomes with increasing VMR, we inferred mVMR across different biomes. To properly estimate mVMR in aquatic ecosystems, we generated metagenomes from co-occurring cellular and viral fractions (>50 kDa-200 µm size-range) in freshwater, seawater and solar saltern ponds (10 metagenomes, 2 control metaviromes). Viruses outnumbered cells in freshwater by ∼13 fold and in plankton from marine and saline waters by ∼2-4 fold. However, across an additional set of 121 diverse non-aquatic metagenomes including microbial mats, microbialites, soils, freshwater and marine sediments and metazoan-associated microbiomes, viruses, on average, outnumbered cells by barely two-fold. Although viruses likely are the most diverse biological entities on Earth, their global numbers might be closer to those of cells than previously estimated.
Published: 2023
Full Text: View/download PDF

10. Deliberative assembling: Tinkering and farmer agency in precision agriculture implementation

Author: Vaughan Higgins, Daniël van der Velden, Noemie Bechtet, Melanie Bryant, Jane Battersby, Melissa Belle, Laurens Klerkx, University of Tasmania [Hobart, Australia] (UTAS), Research Institute for Agricultural, Fisheries and Food (ILVO), AGroécologie, Innovations, teRritoires (AGIR), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Auteur indépendant, Wageningen University and Research [Wageningen] (WUR), AgriFutures Australia PRJ-009181, European Project: 727577,H2020-RUR-2016-2,AgriLink(2017), and European Project: 818194,DESIRA(2019)
Subjects: Assemblage thinking, Sociology and Political Science, Precision agriculture, [SDV]Life Sciences [q-bio], Geography, Planning and Development, WASS, Development, Tinkering, Agency, Technologie and Innovatie, Digital agriculture, Knowledge Technology and Innovation, Kennis, Kennis, Technologie and Innovatie, Support networks, Agriculture 4.0
Abstract: Assemblage thinking is an increasingly influential approach in critical studies of food and farming, and partic-ularly in research on new agri-food technology such as precision agriculture (PA). This research is important in highlighting the distributed forms of power and agency through which farming worlds are assembled, and what these engender for more sustainable and equitable farming futures. However, to date, there has been limited attention to assembling PA from the perspective of farmers, what Legun and Burch (2021) refer to as 'deliberative assembling'. This paper contributes to knowledge in this area by applying post actor network theoretical work to investigate across case studies in Australia, the Netherlands and France, the forms of tinkering by which farmers attempt to make PA workable, and what these engender for farmer agency. Through our analysis, we show that much of the tinkering by farmers is aimed at holding together their own priorities, routines, and experiences with practices inscribed in PA technology, such as dependence on commercial advice, data-driven knowledge, and commitment to a single technological platform/company. Integral to this tinkering work are support networks that include agronomists, advisors, machinery dealers and/or farmer discussion groups. We argue that whilst these support networks are critical to holding together different practices, and making PA workable, they also play a more diverse and nuanced role in PA implementation than what has previously been recognised. Our case studies provide insights into three key forms of tinkering used by farmers in navigating support networks to make PA workable - disconnection, experimentation and trial-and-error, and trade-offs and compromises - and the specific distributions of agency which these tinkering practices engender. In conclusion, we argue that a tinkering lens provides a valuable approach for enabling agri-food scholars to tease out in greater depth delib-erative assembling practices and how these variously open-up or foreclose options for farmers in making PA workable.
Published: 2023
Full Text: View/download PDF

11. Reproductives signature revealed by protein profiling and behavioral bioassays in termite

Author: Ruhland, Fanny, Gabant, Guillaume, Toussaint, Timothée, Nemcic, Matej, Cadène, Martine, Lucas, Christophe, Université de Tours (UT), Institut de recherche sur la biologie de l'insecte UMR7261 (IRBI), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), 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), Université d'Orléans (UO), Région Centre-Val de Loire (APR-IR 2017-00117111 BioControleTermite, APRIA MALDITOF 2018, APR-IA 2012, APR-IA SYMBIOMS 2010), European Project: 773324,ForestValue, and European Project: 508 2699-33931
Subjects: Multidisciplinary, [SDV]Life Sciences [q-bio], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Proteins are known to be social interaction signals in many species in the animal kingdom. Common mediators in mammals and aquatic species, they have seldom been identified as such in insects' behaviors. Yet, they could represent an important component to support social signals in social insects, as the numerous physical contacts between individuals would tend to favor the use of contact compounds in their interactions. However, their role in social interactions is largely unexplored: are they rare or simply underestimated? In this preliminary study, we show that, in the termite Reticulitermes flavipes, polar extracts from reproductives trigger body-shaking of workers (a vibratory behavior involved in reproductives recognition) while extracts from workers do not. Molecular profiling of these cuticular extracts using MALDI-TOF mass spectrometry reveals higher protein diversity in reproductives than in workers and a sex-specific composition exclusive to reproductives. While the effects observed with extracts are not as strong as with live termites, these results open up the intriguing possibility that social signaling may not be limited to cuticular hydrocarbons or other non-polar, volatile chemicals as classically accepted. Our results suggest that polar compounds, in particular some of the Cuticular Protein Compounds (CPCs) shown here by MALDI to be specific to reproductives, could play a significant role in insect societies. While this study is preliminary and further comprehensive molecular characterization is needed to correlate the body-shaking triggering effects with a given set of polar compounds, this exploratory study opens new perspectives for understanding the role of polar compounds such as proteins in caste discrimination, fertility signaling, or interspecific insect communication.
Published: 2023
Full Text: View/download PDF

12. Genetic analysis of global faba bean diversity, agronomic traits and selection signatures

Author: Cathrine Kiel Skovbjerg, Deepti Angra, Tom Robertson-Shersby-Harvie, Jonathan Kreplak, Gabriel Keeble-Gagnère, Sukhjiwan Kaur, Wolfgang Ecke, Alex Windhorst, Linda Kærgaard Nielsen, Andrea Schiemann, Jens Knudsen, Natalia Gutierrez, Vasiliki Tagkouli, Lavinia Ioana Fechete, Luc Janss, Jens Stougaard, Ahmed Warsame, Sheila Alves, Hamid Khazaei, Wolfgang Link, Ana Maria Torres, Donal Martin O’Sullivan, Stig Uggerhøj Andersen, Aarhus University [Aarhus], University of Reading (UOR), Agroécologie [Dijon], Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre for AgriBioscience, Bundoora, Georg-August-University = Georg-August-Universität Göttingen, Sejet Planteforædling, Nordic Seed, IFAPA Centro Alameda del Obispo, Instituto Andaluz de Investigación y Formación Agraria y Pesquera (IFAPA), Crops Research, Teagasc, Oak Park, Carlow, Natural Resources Institute Finland (LUKE), Open access funding provided by Royal Danish Library. Thework was funded by the European Union’s Horizon 2020 Programmefor Research & Innovation (grant agreement no. 727312 for theEUCLEG project, the ERA-NET Cofund SusCrop (grant no. 771134),part of the Joint Programming Initiative on Agriculture, Food Security,and Climate Change (FACCE-JPI) for the ProFaba project), InnovationFund Denmark (NORFAB: Protein for the Northern Hemisphere, grantno. 5158-00004B), and UK Research and Innovation for BEANS4N.AFRICA (grant award BB/P023509/1). The VICCI population wasdeveloped under a doctoral project between the University of Readingand Teagasc and was supported by the Irish Department of Agriculture,Food and the Marine (DAFM), under project 14/S/819 (the VirtualIrish Centre for Crop Improvement). The RSBP population was developed with the support of a PhD fellowship to Ahmed Warsame fromthe Islamic Development Bank, European Project: 771134, and European Project: 727312
Subjects: [SDV]Life Sciences [q-bio], Genetics, General Medicine, Agronomy and Crop Science, Biotechnology
Abstract: Key message We identified marker-trait associations for key faba bean agronomic traits and genomic signatures of selection within a global germplasm collection. Abstract Faba bean (Vicia faba L.) is a high-protein grain legume crop with great potential for sustainable protein production. However, little is known about the genetics underlying trait diversity. In this study, we used 21,345 high-quality SNP markers to genetically characterize 2678 faba bean genotypes. We performed genome-wide association studies of key agronomic traits using a seven-parent-MAGIC population and detected 238 significant marker-trait associations linked to 12 traits of agronomic importance. Sixty-five of these were stable across multiple environments. Using a non-redundant diversity panel of 685 accessions from 52 countries, we identified three subpopulations differentiated by geographical origin and 33 genomic regions subjected to strong diversifying selection between subpopulations. We found that SNP markers associated with the differentiation of northern and southern accessions explained a significant proportion of agronomic trait variance in the seven-parent-MAGIC population, suggesting that some of these traits were targets of selection during breeding. Our findings point to genomic regions associated with important agronomic traits and selection, facilitating faba bean genomics-based breeding.
Published: 2023
Full Text: View/download PDF

13. A review of biodiversity research in ports: Let's not overlook everyday nature!

Author: Madon, Bénédicte, David, Romain, Torralba, Antonio, Jung, Armelle, Marengo, Michel, Thomas, Hélène, LIttoral ENvironnement et Sociétés (LIENSs), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), Universidad de Sevilla / University of Sevilla, European Research Infrastructure on Highly Pathogenic Agents (ERINHA-AISBL), Station de Recherche Océanographiques et sous-marines (STARESO ), Stareso, Pointe Revellata, BP 33, 20260 Calvi, France, This study was carried out in the framework of the EMFF QUAMPO project (grant number PFEA800219DM0940001), Horizon Europe projects MARCO-BOLO (grant number: 101082021) and DANUBIUS-IP (grant number: 101079778). Complementary support was provided through the EOSC-Life European program under grant agreement Nº824087., European Project: 824087,EOSC-Life, European Project: 101082021,MARCO-BOLO, and European Project: 101079778,DANUBIUS-IP
Subjects: Harbor management, Scoping review, Biological diversity, Port, Urban ecosystem, JEL: Q - Agricultural and Natural Resource Economics • Environmental and Ecological Economics, [SDV]Life Sciences [q-bio], [SDE]Environmental Sciences, Harbour, environmental sustainability, Marina
Abstract: International audience; Ports are urban and often quite-confined habitats within the aquatic (marine or freshwater) ecosystems, hostingbiodiversity as any natural ecosystem under anthropogenic pressures as in many urban ecosystems. This scopingreview seeks to give an overview of the state of knowledge on port biodiversity and port concerns aboutbiodiversity based on scientific literature. Our aim was to highlight gaps and strengths in biodiversity knowledgeand research in the port ecosystem, the outcomes of which are supposed to inform port authorities, guide portmanagement and assist in planning research and management actions towards the implementation of relevantmeasures for port environmental sustainability. Results using Web of Science showed a recent trend in portbiodiversity research (no references before 1999, most published after 2016) with a shift of research objectivefrom empirical knowledge early-on towards non-indigenous species (NIS) concern recently. European, commercial ports and the NIS concern dominated the landscape. Fish, invertebrates such as crustaceans, major international and inland (freshwater) ports were under-represented. This review highlighted the need for a shift inport environmental awareness for biodiversity to expect resilience of the whole social-ecological system and forbaseline knowledge and exhaustive inventories to assess how anthropogenic activities impact biodiversity andchange ecosystem properties and functions.
Published: 2023
Full Text: View/download PDF

14. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19

Author: Bradbury, Charlotte A., Lawler, Patrick R., Stanworth, Simon J., McVerry, Bryan J., McQuilten, Zoe, Higgins, Alisa M., Mouncey, Paul R., Al-Beidh, Farah, Rowan, Kathryn M., Berry, Lindsay R., Lorenzi, Elizabeth, Zarychanski, Ryan, Arabi, Yaseen M., Annane, Djillali, Beane, Abi, Van Bentum-Puijk, Wilma, Bhimani, Zahra, Bihari, Shailesh, Bonten, Marc J. M., Brunkhorst, Frank M., Buzgau, Adrian, Buxton, Meredith, Carrier, Marc, Cheng, Allen C., Cove, Matthew, Detry, Michelle A., Estcourt, Lise J., Fitzgerald, Mark, Girard, Timothy D., Goligher, Ewan C., Goossens, Herman, Haniffa, Rashan, Hills, Thomas, Huang, David T., Horvat, Christopher M., Hunt, Beverley J., Ichihara, Nao, Lamontagne, Francois, Leavis, Helen L., Linstrum, Kelsey M., Litton, Edward, Marshall, John C., McAuley, Daniel F., McGlothlin, Anna, McGuinness, Shay P., Middeldorp, Saskia, Montgomery, Stephanie K., Morpeth, Susan C., Murthy, Srinivas, Neal, Matthew D., Nichol, Alistair D., Parke, Rachael L., Parker, Jane C., Reyes, Luis, Saito, Hiroki, Santos, Marlene S., Saunders, Christina T., Serpa-Neto, Ary, Seymour, Christopher W., Shankar-Hari, Manu, Singh, Vanessa, Tolppa, Timo, Turgeon, Alexis F., Turner, Anne M., van de Veerdonk, Frank L., Green, Cameron, Lewis, Roger J., Angus, Derek C., McArthur, Colin J., Berry, Scott, Derde, Lennie P. G., Webb, Steve A., Gordon, Anthony C., Depuydt, Pieter, De Waele, Jan, De Bus, Liesbet, Fierens, Jan, Vermassen, Joris, REMAP-CAP Investigators, University of Bristol [Bristol], University Health Network, University of Toronto, University of Oxford, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Monash University [Melbourne], Imperial College London, University of Manitoba [Winnipeg], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University Medical Center [Utrecht], St. Michael's Hospital, 215522, CS-2016-16-011, RP-2015-06-18, National Institutes of Health, NIH, U.S. Department of Defense, DOD, National Institute of General Medical Sciences, NIGMS, National Institute of Neurological Disorders and Stroke, NINDS, Gordon and Betty Moore Foundation, GBMF, Medtronic, Baxter International, Medical Center, University of Pittsburgh, CancerCare Manitoba Foundation, CCMF, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD, Wellcome Trust, WT, Health Research Board, HRB: CTN 2014-012, Horizon 2020 Framework Programme, H2020: 101003589, LAM Therapeutics, Canadian Institutes of Health Research, IRSC: 158584, Medical Research Council, MRC, National Institute for Health and Care Research, NIHR, European Commission, EC, National Heart and Lung Institute, NHLI, Queen's University Belfast, QUB: US8962032, National Health and Medical Research Council, NHMRC: APP1101719, National Medical Research Council, NMRC, Health Research Council of New Zealand, HRC: 16/631, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Innovate UK, Horizon 2020, Pharmaceuticals Bayer, Swedish Orphan Biovitrum, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, Funding/Support: This study was funded by the following: the Platform for European Preparedness Against (Re-)Emerging Epidemics (PREPARE) consortium of the European Union, FP7-HEALTH-2013-INNOVATION-1 (grant 602525), the Rapid European COVID-19 Emergency Research Response (RECOVER) consortium of the European Union’s Horizon 2020 Research and Innovation Programme (grant 101003589), the Australian National Health and Medical Research Council (grant APP1101719), the Health Research Council of New Zealand (grant 16/631), the Canadian Institute of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program (grant 158584), the NIHR and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (grant CTN 2014-012), the University of Pittsburgh Medical Center (UPMC) Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (grant PHRC-20-0147), the Minderoo Foundation, and the Wellcome Trust Innovations Project (grant 215522). Dr Shankar-Hari is funded by an NIHR clinician scientist fellowship (grant CS-2016-16-011) and Dr Gordon is funded by an NIHR research professorship (grant RP-2015-06-18)., The REMAP-CAP platform is supported by the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Canadian Critical Care Clinical Trials Group, the Irish Critical Care Clinical Trials Network, the UK Critical Care Research Group and the International Forum of Acute Care Trialists., REMAP-CAP was supported in the Netherlands by the Research Collaboration Critical Care the Netherlands, reported receipt of personal fees from Lilly, BMS-Pfizer, Bayer, Amgen, Novartis, Janssen, Portola, Ablynx, and Grifols. Dr Lawler reported receipt of personal fees from Novartis, CorEvitas, and Brigham and Women’s Hospital and royalties from McGraw-Hill Publishing. Dr McVerry reported receipt of grants from the National Heart, Lung, and Blood Institute and Bayer Pharmaceuticals and personal fees from Boehringer Ingelheim. Dr L. Berry reported being an employee of Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Lorenzi reported being an employee of Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Zarychanski reported receipt of grants from the Canadian Institutes of Health Research, LifeArc, Research Manitoba, the CancerCare Manitoba Foundation, Peter Munk Cardiac Centre, and the Thistledown Foundation and research operating support as the Lyonel G. Israels Research Chair in Hematology. Dr Bonten reported membership in international study steering committees, advisory boards, and independent data safety and monitoring committees funded by Janssen Vaccines, Merck Sharp & Dohme, AstraZeneca, Pfizer, and Sanofi Pasteur (all reimbursements to UMC Utrecht). Dr Brunkhorst reported receipt of grants from Jena University Hospital. Dr Buxton reported receipt of a gift from the Breast Cancer Research Foundation and contracts with Amgen and Eisai. Dr Carrier reported receipt of grants from BMS-Pfizer and personal fees from Bayer, Sanofi, Servier, Leo Phama, and BMS-Pfizer to his institution. Dr Cove reported receipt of grants from the National Medical Research Council and personal fees from Baxter and Medtronic. Dr Estcourt reported receipt of grants from the UK National Institute for Health Research (NIHR) and the European Union Horizon 2020 Research and Innovation Programme. Dr Haniffa reported receipt of grants from the UK Research and Innovation/Medical Research Council African Critical Care Registry Network. Dr Horvat reported receipt of grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. Dr Ichihara reported being affiliated with the Department of Healthcare Quality Assessment, University of Tokyo, which is a social collaboration supported by the National Clinical Database, Johnson & Johnson, and Nipro Corporation. Dr Marshall reported receipt of personal fees from AM Pharma and Critical Care Medicine. Dr McAuley reported receipt of personal fees from Bayer, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Lilly, Vir Biotechnology, Faron Pharmaceutical, and SOBI and grants from the NIHR, the Wellcome Trust, Innovate UK, the UK Medical Research Council, and the Northern Ireland Health and Social Care Research and Development Division, in addition, Dr McAuley had a Queen’s University Belfast patent for novel treatment for inflammatory disease (US8962032), was co-director of research at the Intensive Care Society until June 2021, and was director of the Efficacy and Mechanisms Evaluation Program for the UK Medical Research Council/NIHR. Dr Middeldorp reported receipt of personal fees from Daiichi Sankyo, Bayer, Pfizer, Boehringer Ingelheim, Portola/Alexion, AbbVie, BMS-Pfizer, Sanofi, and Viatris, all paid to his institution, and grants from Daiichi Sankyo, Bayer, Pfizer, and Boehringer Ingelheim. Dr Neal reported equity in Haima Therapeutics, receipt of personal fees from Janssen Pharma and Haemonetics, and receipt of grants from Instrumentation Laboratory, the National Institutes of Health, and the Department of Defense. Dr Nichol reported receipt of personal fees from AM Pharma, paid to his university, and grants from Baxter. Dr Parke reported receipt of grants from Fisher and Paykel Healthcare NZ. Dr Serpa-Neto reported receipt of personal fees from Drager and Endpoint Health. Dr Seymour reported receipt of grants from the Gordon and Betty Moore Foundation and the National Institutes of Health/National Institute of General Medical Sciences. Dr Lewis reported being senior medical scientist at Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr S. Berry reported being an employee with an ownership role at Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Derde reported being a coordinating committee member for the European Clinical Research Alliance on Infectious Diseases, a member of the Dutch Intensivists Task Force on Acute Infectious Threats, a member of the International Scientific Advisory Board for Sepsis Canada, and a member of the Dutch Academy of Sciences’ Pandemic Preparedness Plan committee. Dr Gordon reported receipt of personal fees from 30 Respiratory, paid to his institution. No other disclosures were reported., European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), Investigators, REMAP-CAP Writing Committee for the REMAP-CAP, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, and Intensive Care Medicine
Subjects: Adult, Male, Platelet Aggregation Inhibitors/adverse effects, Critical Illness, [SDV]Life Sciences [q-bio], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Hemorrhage, Aspirin/adverse effects, Hemorrhage/chemically induced, INFECTION, Humans, COAGULOPATHY, Aspirin, Anticoagulants, COVID-19, Bayes Theorem, Venous Thromboembolism, General Medicine, Middle Aged, Respiration, Artificial, COVID-19 Drug Treatment, Critical Illness/mortality, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Purinergic P2Y Receptor Antagonists/adverse effects, Purinergic P2Y Receptor Antagonists, COVID-19/complications, Female, Human medicine, Anticoagulants/adverse effects, Platelet Aggregation Inhibitors, Venous Thromboembolism/drug therapy
Abstract: Contains fulltext : 248713.pdf (Publisher’s version ) (Closed access) IMPORTANCE: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. OBJECTIVE: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). INTERVENTIONS: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. MAIN OUTCOMES AND MEASURES: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. RESULTS: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). CONCLUSIONS AND RELEVANCE: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.
Published: 2022
Full Text: View/download PDF

15. Minimizing school disruption under high incidence conditions due to the Omicron variant in France, Switzerland, Italy in January 2022

Author: Elisabetta Colosi, Giulia Bassignana, Alain Barrat, Bruno Lina, Philippe Vanhems, Julia Bielicki, Vittoria Colizza, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Physique Théorique - UMR 7332 (CPT), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), National Reference Center for Respiratory Viruses, Department of Virology, Infective Agents Institute, Croix-Rousse Hospital, Hospices Civils de Lyon, Service d'Hygiène, Épidémiologie, Infectiovigilance et Prévention, Hospices Civils de Lyon, Paediatric Infectious Diseases, University of Basel Children's Hospital, ANR-21-CO16-0005,Coscreen,Définition et évaluation de stratégies de dépistage du Covid screening dans des contextes variés, à partir de données de contact empiriques(2021), ANR-19-CE46-0008,DataRedux,Réduction de données massives pour la simulation numérique prédictive(2019), European Project: EU H2020 - MOOD, European Project: RECOVER, and European Project: EU HORIZON - VERDI
Subjects: Epidemiology, Omicron, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, COVID-19, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, schools, resources, vaccination, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, testing
Abstract: Background As record cases of Omicron variant were registered in Europe in early 2022, schools remained a vulnerable setting undergoing large disruption. Aim Through mathematical modelling, we compared school protocols of reactive screening, regular screening, and reactive class closure implemented in France, in Baselland (Switzerland), and in Italy, respectively, and assessed them in terms of case prevention, testing resource demand, and schooldays lost. Methods We used a stochastic agent-based model of SARS-CoV-2 transmission in schools accounting for within- and across-class contacts from empirical contact data. We parameterised it to the Omicron BA.1 variant to reproduce the French Omicron wave in January 2022. We simulated the three protocols to assess their costs and effectiveness for varying peak incidence rates in the range experienced by European countries. Results We estimated that at the high incidence rates registered in France during the Omicron BA.1 wave in January 2022, the reactive screening protocol applied in France required higher test resources compared with the weekly screening applied in Baselland (0.50 vs 0.45 tests per student-week), but achieved considerably lower control (8% vs 21% reduction of peak incidence). The reactive class closure implemented in Italy was predicted to be very costly, leading to > 20% student-days lost. Conclusions At high incidence conditions, reactive screening protocols generate a large and unplanned demand in testing resources, for marginal control of school transmissions. Comparable or lower resources could be more efficiently used through weekly screening. Our findings can help define incidence levels triggering school protocols and optimise their cost-effectiveness.
Published: 2023
Full Text: View/download PDF

16. Clonal hematopoiesis driven by chromosome 1q/MDM4 trisomy defines a canonical route toward leukemia in Fanconi anemia

Author: Marie Sebert, Stéphanie Gachet, Thierry Leblanc, Alix Rousseau, Olivier Bluteau, Rathana Kim, Raouf Ben Abdelali, Flore Sicre de Fontbrune, Loïc Maillard, Carèle Fedronie, Valentine Murigneux, Léa Bellenger, Naira Naouar, Samuel Quentin, Lucie Hernandez, Nadia Vasquez, Mélanie Da Costa, Pedro H. Prata, Lise Larcher, Marie de Tersant, Matthieu Duchmann, Anna Raimbault, Franck Trimoreau, Odile Fenneteau, Wendy Cuccuini, Nathalie Gachard, Nathalie Auger, Giulia Tueur, Maud Blanluet, Claude Gazin, Michèle Souyri, Francina Langa Vives, Aaron Mendez-Bermudez, Hélène Lapillonne, Etienne Lengline, Emmanuel Raffoux, Pierre Fenaux, Lionel Adès, Edouard Forcade, Charlotte Jubert, Carine Domenech, Marion Strullu, Bénédicte Bruno, Nimrod Buchbinder, Caroline Thomas, Arnaud Petit, Guy Leverger, Gérard Michel, Marina Cavazzana, Eliane Gluckman, Yves Bertrand, Nicolas Boissel, André Baruchel, Jean-Hugues Dalle, Emmanuelle Clappier, Eric Gilson, Ludovic Deriano, Sylvie Chevret, François Sigaux, Gérard Socié, Dominique Stoppa-Lyonnet, Hugues de Thé, Christophe Antoniewski, Dominique Bluteau, Régis Peffault de Latour, Jean Soulier, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP Hôpital universitaire Robert-Debré [Paris], Recherche clinique appliquée à l'hématologie (URP_3518), 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), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Institut Gustave Roussy (IGR), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Ingénierie génétique murine - Mouse Genetics Engineering Center (CIGM), Institut Pasteur [Paris] (IP), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpitaux universitaires Est parisien [AP-HP], CHU Bordeaux [Bordeaux], Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Rouen, Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), CIC NECKER BT (CIC 1416), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Collège de France (CdF (institution)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL), This study received support from the European Research Council (ERC) Consolidator Grant to J.S. (CEVAL-311660), the FP7 Eurofancolen program (HEALTH-F5-2012-305421), the ANR program PACRI (Projet alliance parisienne des instituts de recherche en cancérologie), the CONECT-AML (Collaborative Network for Children and Teenagers with Acute Myeloid Leukemia) program supported by a grant from the Institut National du Cancer (INCa), Fondation ARC, Ligue nationale contre le cancer, and Laurette Fugain (INCa-ARC-LIGUE_11905) to J.S. and C.A., and the Association Française pour la Maladie de Fanconi (AFMF) grants 'Histoire naturelle de la maladie de Fanconi' to R.P.L. and J.S., 'Modélisation de la transformation leucémique dans la maladie de Fanconi' to D.B., and 'Cribles fonctionnels à haut débit de gènes modificateurs de la maladie de Fanconi' to C.G. M.S. was supported by the AVIESAN-INCa Program 'Formation à la Recherche Translationnelle,' and A.R. by a grant from the Fondation ARC. The work in E.G.’s lab is supported by Fondation ARC and ANR Telochrom. The work in L.D.’s lab is supported by INCa (PLBIO16-181) and ERC (310917)., ANR-11-PHUC-0002,PACRI,Alliance Parisienne des Instituts de Recherche en Cancérologie(2011), European Project: 311660,EC:FP7:ERC,ERC-2012-StG_20111109,CEVAL(2013), and European Project: 305421,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,EUROFANCOLEN(2013)
Subjects: MDM4, Fanconi anemia, precision medicine, [SDV]Life Sciences [q-bio], Genetics, leukemia, clonal hematopoiesis, Molecular Medicine, Cell Biology, TP53, mutational signature, genomic instability, BRCA2
Abstract: International audience; Fanconi anemia (FA) patients experience chromosome instability, yielding hematopoietic stem/progenitor cell (HSPC) exhaustion and predisposition to poor-prognosis myeloid leukemia. Based on a longitudinal cohort of 335 patients, we performed clinical, genomic, and functional studies in 62 patients with clonal evolution. We found a unique pattern of somatic structural variants and mutations that shares features of BRCA-related cancers, the FA-hallmark being unbalanced, microhomology-mediated translocations driving copy-number alterations. Half the patients developed chromosome 1q gain, driving clonal hematopoiesis through MDM4 trisomy downmodulating p53 signaling later followed by secondary acute myeloid lukemia genomic alterations. Functionally, MDM4 triplication conferred greater fitness to murine and human primary FA HSPCs, rescued inflammation-mediated bone marrow failure, and drove clonal dominance in FA mouse models, while targeting MDM4 impaired leukemia cells in vitro and in vivo. Our results identify a linear route toward secondary leukemogenesis whereby early MDM4-driven downregulation of basal p53 activation plays a pivotal role, opening monitoring and therapeutic prospects.
Published: 2023
Full Text: View/download PDF

17. 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
Full Text: View/download PDF

18. Clinical and prognostic associations of autoantibodies recognizing adrenergic/muscarinic receptors in patients with heart failure

Author: Markousis-Mavrogenis, George, Minich, Waldemar B, Al-Mubarak, Ali A, Anker, Stefan D, Cleland, John G F, Dickstein, Kenneth, Lang, Chim C, Leong L, Ng, Samani, Nilesh J, Zannad, Faiez, Metra, Marco, Seemann, Petra, Hoeg, Antonia, Lopez, Patricio, van Veldhuisen, Dirk J, de Boer, Rudolf A, Voors, Adriaan A, van der Meer, Peter, Schomburg, Lutz, Bomer, Nils, University Medical Center Groningen [Groningen] (UMCG), University of Groningen [Groningen], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], ImmunometriX GmbH i.L., Charité Campus Virchow-Klinikum (CVK), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University Medical Center Göttingen (UMG), University of Glascow, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University of Bergen (UiB), Stavanger University Hospital, University of Dundee, Department of Cardiovascular Sciences [Leicester], University of Leicester, NIHR Leicester Cardiovascular Biomedical Research Unit, 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), 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 ), University of Brescia, Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), and European Project
Subjects: immune system, Physiology, Physiology (medical), [SDV]Life Sciences [q-bio], autoimmunity, M2, beta 1, beta 2, beta 3, Cardiology and Cardiovascular Medicine, beta 1 beta 2 beta 3 M2 immune system autoimmunity
Abstract: AimsThe importance of autoantibodies (AABs) against adrenergic/muscarinic receptors in heart failure (HF) is not well-understood. We investigated the prevalence and clinical/prognostic associations of four AABs recognizing the M2-muscarinic receptor or the β1-, β2-, or β3-adrenergic receptor in a large and well-characterized cohort of patients with HF.Methods and resultsSerum samples from 2256 patients with HF from the BIOSTAT-CHF cohort and 299 healthy controls were analysed using newly established chemiluminescence immunoassays. The primary outcome was a composite of all-cause mortality and HF rehospitalization at 2-year follow-up, and each outcome was also separately investigated. Collectively, 382 (16.9%) patients and 37 (12.4%) controls were seropositive for ≥1 AAB (P = 0.045). Seropositivity occurred more frequently only for anti-M2 AABs (P = 0.025). Amongst patients with HF, seropositivity was associated with the presence of comorbidities (renal disease, chronic obstructive pulmonary disease, stroke, and atrial fibrillation) and with medication use. Only anti-β1 AAB seropositivity was associated with the primary outcome [hazard ratio (95% confidence interval): 1.37 (1.04–1.81), P = 0.024] and HF rehospitalization [1.57 (1.13–2.19), P = 0.010] in univariable analyses but remained associated only with HF rehospitalization after multivariable adjustment for the BIOSTAT-CHF risk model [1.47 (1.05–2.07), P = 0.030]. Principal component analyses showed considerable overlap in B-lymphocyte activity between seropositive and seronegative patients, based on 31 circulating biomarkers related to B-lymphocyte function.ConclusionsAAB seropositivity was not strongly associated with adverse outcomes in HF and was mostly related to the presence of comorbidities and medication use. Only anti-β1 AABs were independently associated with HF rehospitalization. The exact clinical value of AABs remains to be elucidated.
Published: 2023
Full Text: View/download PDF

19. Abolishment of morphology-based taxa and change to binomial species names: 2022 taxonomy update of the ICTV bacterial viruses subcommittee

Author: Dann Turner, Andrey N. Shkoporov, Cédric Lood, Andrew D. Millard, Bas E. Dutilh, Poliane Alfenas-Zerbini, Leonardo J. van Zyl, Ramy K. Aziz, Hanna M. Oksanen, Minna M. Poranen, Andrew M. Kropinski, Jakub Barylski, J Rodney Brister, Nina Chanisvili, Rob A. Edwards, François Enault, Annika Gillis, Petar Knezevic, Mart Krupovic, Ipek Kurtböke, Alla Kushkina, Rob Lavigne, Susan Lehman, Malgorzata Lobocka, Cristina Moraru, Andrea Moreno Switt, Vera Morozova, Jesca Nakavuma, Alejandro Reyes Muñoz, Jānis Rūmnieks, BL Sarkar, Matthew B. Sullivan, Jumpei Uchiyama, Johannes Wittmann, Tong Yigang, Evelien M. Adriaenssens, UCL - SST/ELI/ELIM - Applied Microbiology, University of the West of England [Bristol] (UWE Bristol), University College Cork (UCC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Leicester, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Utrecht University [Utrecht], Universidade Federal de Viçosa = Federal University of Viçosa (UFV), University of the Western Cape (UWC), Cairo University, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Guelph, Adam Mickiewicz University in Poznań (UAM), National Center for Biotechnology Information (NCBI), George Eliava Institute of Bacteriophages, Microbiology and Virology [Tbilisi, Georgia], Flinders Accelerator for Microbiome Exploration [Adelaide, Australia], Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Université Catholique de Louvain = Catholic University of Louvain (UCL), University of Novi Sad, Virologie des archées - Archaeal Virology, 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), University of the Sunshine Coast (USC), D.K. Zabolotny Institute of Microbiology and Virology [Kyiv, Ukraine], National Academy of Sciences of Ukraine (NASU), University of Gdańsk (UG), Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (FDA), Institute of Biochemistry and Biophysics [Warsaw] (IBB), University of Oldenburg, Pontificia Universidad Católica de Chile (UC), Institute of Chemical Biology and Fundamental Medicine [Novosibirsk, Russia] (ICBFM SB RAS), Siberian Branch of the Russian Academy of Sciences (SB RAS), Makerere University [Kampala, Ouganda] (MAK), Universidad de los Andes [Bogota] (UNIANDES), Latvian Biomedical Research and Study Center (BMC), National Institute of Cholera and Enteric Diseases, Ohio State University [Columbus] (OSU), Okayama University, Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH / Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures (DSMZ), Beijing University of Chemical Technology, Quadram Institute Bioscience [Norwich, U.K.] (QIB), Biotechnology and Biological Sciences Research Council (BBSRC), B.E.D. was supported by the European Research Council (ERC) Consolidator Grant 865694: DiversiPHI, the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – EXC 2051 – Project-ID 390713860, the Alexander von Humboldt Foundation in the context of an Alexander von Humboldt Professorship funded by the German Federal Ministry of Education and Research, and the European Union’s Horizon 2020 Research and Innovation Program, under the Marie Skłodowska-Curie Actions Innovative Training Networks grant agreement no. 955974 (VIROINF). Work by J.R.B. was supported by the National Center for Biotechnology Information of the National Library of Medicine (NLM), National Institutes of Health. R.A.E was supported by an award from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institute of Health RC2DK116713 and an award from the Australian Research Council, DP220102915. R.L. is supported by the research grant PHAGEFORCE from the KU Leuven. C.L. is supported by the Research Foundation - Flanders (FWO Grant 12D8623N) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – EXC 2051 – Project-ID 390713860. V.M. is supported by the Russian state-funded project For ICBFM SB RAS, Grant 121031300043-8. H.M.O. was supported by the University of Helsinki and Academy of Finland by funding for FINStruct and Instruct Centre Finland, Instruct-ERIC. M.M.P. acknowledges funding from the Sigrid Jusélius Foundation and the Academy of Finland (grant 331627). A.N.S is supported by a Wellcome Trust Research Career Development Fellowship [220646/Z/20/Z] and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No 101001684). E.M.A. gratefully acknowledges funding by the Biotechnology and Biological Sciences Research Council (BBSRC), this research was funded by the BBSRC Institute Strategic Programme Gut Microbes and Health BB/R012490/1 and its constituent projects BBS/E/F/000PR10353 and BBS/E/F/000PR10356., European Project: 865694,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC),DiversiPHI(2020), and European Project: 101001684,ERC-2020-COG,PHAGENET(2021)
Subjects: Science & Technology, [SDV]Life Sciences [q-bio], Virology, General Medicine, Life Sciences & Biomedicine
Abstract: This article summarises the activities of the Bacterial Viruses Subcommittee of the International Committee on Taxonomy of Viruses for the period of March 2021−March 2022. We provide an overview of the new taxa proposed in 2021, approved by the Executive Committee, and ratified by vote in 2022. Significant changes to the taxonomy of bacterial viruses were introduced: the paraphyletic morphological families Podoviridae, Siphoviridae, and Myoviridae as well as the order Caudovirales were abolished, and a binomial system of nomenclature for species was established. In addition, one order, 22 families, 30 subfamilies, 321 genera, and 862 species were newly created, promoted, or moved.
Published: 2023
Full Text: View/download PDF

20. Greedy reduction of Bacillus subtilis genome yields emergent phenotypes of high resistance to a DNA damaging agent and low evolvability

Author: Etienne Dervyn, Anne-Gaëlle Planson, Kosei Tanaka, Victor Chubukov, Cyprien Guérin, Sandra Derozier, François Lecointe, Uwe Sauer, Ken-Ichi Yoshida, Pierre Nicolas, Philippe Noirot, Matthieu Jules, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute of Molecular Systems Biology [Zurich], Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Konan University [Kobe, Japan], European Commission [LSHG-CT-2006-037469, FP7-244093], ANR-18-CE44-0003,Bacillus2-0,Construction et transplantation de génomes semi-synthétiques de Bacillus subtilis, vers le développement de la prochaine génération de châssis bactériens(2018), ANR-18-CE43-0002,BioBrickEvolver,Développement d'un système pour la production de biobriques par évolution dirigée dans la bactérie Bacillus subtilis(2018), ANR-15-CE21-0008,MEM,Apprentissage automatique au service de l'ingénierie métabolique(2015), European Project: LSHG-CT-2006–07900, and European Project: 244093,EC:FP7:KBBE,FP7-KBBE-2009-3,BASYNTHEC(2010)
Subjects: [SDV]Life Sciences [q-bio], Genetics
Abstract: Genome-scale engineering enables rational removal of dispensable genes in chassis genomes. Deviating from this approach, we applied greedy accumulation of deletions of large dispensable regions in the Bacillus subtilis genome, yielding a library of 298 strains with genomes reduced up to 1.48 Mb in size. High-throughput physiological phenotyping of these strains confirmed that genome reduction is associated with substantial loss of cell fitness and accumulation of synthetic-sick interactions. Transcriptome analysis indicated that 300-fold) to the DNA-damaging agent mitomycin C and a very low spontaneous mutagenesis (reduced 100-fold). Adaptive laboratory evolution failed to restore cell fitness, except when coupled with a synthetic increase of the mutation rate, confirming low evolvability. Although mechanisms underlying this emergent phenotype are not understood, we propose that low evolvability can be leveraged in an engineering strategy coupling reductive cycles with evolutive cycles under induced mutagenesis., Nucleic Acids Research, 51 (6), ISSN:1362-4962, ISSN:0301-5610
Published: 2023
Full Text: View/download PDF

21. <scp>DNA</scp> damage repair kinase <scp>DNA‐PK</scp> and <scp>cGAS</scp> synergize to induce cancer‐related inflammation in glioblastoma

Author: Clara Taffoni, Johanna Marines, Hanane Chamma, Soumyabrata Guha, Mathilde Saccas, Amel Bouzid, Ana‐Luiza Chaves Valadao, Clément Maghe, Jane Jardine, Mi Kyung Park, Katarzyna Polak, Mara De Martino, Claire Vanpouille‐Box, Maguy Del Rio, Celine Gongora, Julie Gavard, Nicolas Bidère, Min Sup Song, Donovan Pineau, Jean‐Philippe Hugnot, Karima Kissa, Laura Fontenille, Fabien P Blanchet, Isabelle K Vila, Nadine Laguette, Institut de génétique humaine (IGH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), AZELEAD, Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Texas M.D. Anderson Cancer Center [Houston], Weill Cornell Medicine [Cornell University], Cornell University [New York], Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Laboratory of Pathogen and Host Immunity [Montpellier] (LPHI), Institut de Recherche en Infectiologie de Montpellier (IRIM), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), European Project: 637763,H2020,ERC-2014-STG,CrIC(2015), and European Project: 893772,DIM-CrIC
Subjects: DNA-PK, General Immunology and Microbiology, inflammation, [SDV]Life Sciences [q-bio], General Neuroscience, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Molecular Biology, tumor immunogenicity, General Biochemistry, Genetics and Molecular Biology, cGAS
Abstract: International audience; Cytosolic DNA promotes inflammatory responses upon detection by the cyclic GMP-AMP (cGAMP) synthase (cGAS). It has been suggested that cGAS downregulation is an immune escape strategy harnessed by tumor cells. Here, we used glioblastoma cells that show undetectable cGAS levels to address if alternative DNA detection pathways can promote pro-inflammatory signaling. We show that the DNA-PK DNA repair complex (i) drives cGAS-independent IRF3-mediated type I Interferon responses and (ii) that its catalytic activity is required for cGAS-dependent cGAMP production and optimal downstream signaling. We further show that the cooperation between DNA-PK and cGAS favors the expression of chemokines that promote macrophage recruitment in the tumor microenvironment in a glioblastoma model, a process that impairs early tumorigenesis but correlates with poor outcome in glioblastoma patients. Thus, our study supports that cGAS-dependent signaling is acquired during tumorigenesis and that cGAS and DNA-PK activities should be analyzed concertedly to predict the impact of strategies aiming to boost tumor immunogenicity.
Published: 2022
Full Text: View/download PDF

22. Structure and dynamics of the unassembled nucleoprotein of rabies virus in complex with its phosphoprotein chaperone module

Author: Francine C. A. Gérard, Jean-Marie Bourhis, Caroline Mas, Anaïs Branchard, Duc Duy Vu, Sylvia Varhoshkova, Cédric Leyrat, Marc Jamin, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-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), Integrated Structural Biology Grenoble (ISBG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Graduate School (EUR) CBH—Chemistry, Biology, and Health, Grenoble Instruct-ERIC center (ISBG), European Synchrotron Radiation Facility, Synchrotron SOLEIL, ANR-12-BSV8-0025,NNViPol,Structure et fonction de la machine de transcription et réplication des virus à ARN non-segmenté de polarité négative(2012), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), European Project: 263186,EC:FP7:SPA,FP7-SPACE-2010-1,GRAAL(2011), and European Project: DEQ20170336754
Subjects: [SDV]Life Sciences [q-bio], MESH: Phosphoproteins, nucleocapsid assembly, MESH: RNA, Virology, MESH: Protein Binding, rabies virus, X-ray crystallography, MESH: Nucleocapsid Proteins, Nucleocapsid Proteins, Phosphoproteins, phosphoprotein, MESH: Rabies virus, Infectious Diseases, Nucleoproteins, molecular dynamics simulation, MESH: RNA, Viral, small-angle X-ray scattering, MESH: Nucleoproteins, RNA, RNA, Viral, Mononegavirales, MESH: Molecular Chaperones, Protein Binding, Molecular Chaperones
Abstract: International audience; As for all non-segmented negative RNA viruses, rabies virus has its genome packaged in a linear assembly of nucleoprotein (N), named nucleocapsid. The formation of new nucleocapsids during virus replication in cells requires the production of soluble N protein in complex with its phosphoprotein (P) chaperone. In this study, we reconstituted a soluble heterodimeric complex between an armless N protein of rabies virus (RABV), lacking its N-terminal subdomain (NNT-ARM), and a peptide encompassing the N$^0$ chaperon module of the P protein. We showed that the chaperone module undergoes a disordered−order transition when it assembles with N$^0$ and measured an affinity in the low nanomolar range using a competition assay. We solved the crystal structure of the complex at a resolution of 2.3 Å, unveiling the details of the conserved interfaces. MD simulations showed that both the chaperon module of P and RNA-mediated polymerization reduced the ability of the RNA binding cavity to open and close. Finally, by reconstituting a complex with full-length P protein, we demonstrated that each P dimer could independently chaperon two N$^0$ molecules.
Published: 2022
Full Text: View/download PDF

23. Structural basis of tankyrase activation by polymerization

Author: Nisha Pillay, Laura Mariotti, Mariola Zaleska, Oviya Inian, Matthew Jessop, Sam Hibbs, Ambroise Desfosses, Paul C. R. Hopkins, Catherine M. Templeton, Fabienne Beuron, Edward P. Morris, Sebastian Guettler, The Institute of Cancer Research (ICR), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-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), Diamond Light Source for the cryo-EM facilities at the UK's national Electron Bio-imaging Centre, ICR Light Microscopy Facility, European Project: C47521/A16217, European Project: C47521/A28286, and European Project: EM28549,eBIC
Subjects: Tankyrases, MESH: Enzyme Activation, Multidisciplinary, [SDV]Life Sciences [q-bio], Cryoelectron Microscopy, Amino Acid Motifs, MESH: beta Catenin, MESH: Wnt Signaling Pathway, MESH: Catalytic Domain, Polymerization, Enzyme Activation, MESH: Amino Acid Motifs, MESH: Polymerization, Catalytic Domain, Biocatalysis, MESH: Cryoelectron Microscopy, MESH: Tankyrases, Wnt Signaling Pathway, MESH: Biocatalysis, beta Catenin
Abstract: The poly-ADP-ribosyltransferase tankyrase (TNKS, TNKS2) controls a wide range of disease-relevant cellular processes, including WNT–β-catenin signalling, telomere length maintenance, Hippo signalling, DNA damage repair and glucose homeostasis1,2. This has incentivized the development of tankyrase inhibitors. Notwithstanding, our knowledge of the mechanisms that control tankyrase activity has remained limited. Both catalytic and non-catalytic functions of tankyrase depend on its filamentous polymerization3–5. Here we report the cryo-electron microscopy reconstruction of a filament formed by a minimal active unit of tankyrase, comprising the polymerizing sterile alpha motif (SAM) domain and its adjacent catalytic domain. The SAM domain forms a novel antiparallel double helix, positioning the protruding catalytic domains for recurring head-to-head and tail-to-tail interactions. The head interactions are highly conserved among tankyrases and induce an allosteric switch in the active site within the catalytic domain to promote catalysis. Although the tail interactions have a limited effect on catalysis, they are essential to tankyrase function in WNT–β-catenin signalling. This work reveals a novel SAM domain polymerization mode, illustrates how supramolecular assembly controls catalytic and non-catalytic functions, provides important structural insights into the regulation of a non-DNA-dependent poly-ADP-ribosyltransferase and will guide future efforts to modulate tankyrase and decipher its contribution to disease mechanisms.
Published: 2022
Full Text: View/download PDF

24. A new flavi-like virus identified in populations of wild carrots

Author: Deborah Schönegger, Armelle Marais, Chantal Faure, Thierry Candresse, Biologie du fruit et pathologie (BFP), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This study was funded by the European Union through a Horizon 2020 Marie Skłodowska-Curie Actions Innovative Training Network (H2020 MSCA- 60 ITN) project 'INEXTVIR' (GA 813542)., European Project: 813542,INEXTVIR, and European Project: H2020 MSCA-60 ITN
Subjects: Koshovirus, [SDV]Life Sciences [q-bio], carrot flavi-like virus 1, Daucus carota subsp. carota, Genome, Viral, carotte sauvage, General Medicine, RNA-Dependent RNA Polymerase, Daucus carota, Plant Viruses, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, Open Reading Frames, Virology, RNA Viruses, RNA, Viral, identification, Hts, Amino Acids, Phylogeny, RNA Helicases, Polyproteins, RNA, Double-Stranded
Abstract: We report the discovery of a new flavi-like virus identified in wild carrots (Daucus carota subsp. carota), using a double-stranded (ds)RNA high-throughput sequencing (HTS) approach. The new virus, tentatively named "carrot flavi-like virus 1" (CtFLV-1), has a large genome of 21.8 kb that harbours a single open reading frame encoding a 7,078-aa polyprotein with conserved RNA helicase (Hel) and RNA-dependent RNA polymerase (RdRp) domains. The new virus is phylogenetically related to recently described flavi-like viruses from arthropods, but its closest relative is a plant-associated virus, gentian Kobu-sho-associated virus (GKSaV). A pairwise comparison showed that these two viruses share 38.4% amino acid (aa) sequence identity in their polyproteins and 73% and 47.8% aa sequence identity in their conserved RdRp and Hel domains, respectively. Based on their similar genome organization and phylogenetic relationship, GKSaV and CtFLV-1 could form the basis for a new genus of plant-associated viruses, possibly within the family Flaviviridae, for which the name "Koshovirus" is proposed.
Published: 2022
Full Text: View/download PDF

25. H2020 Projects on Animal Welfare: PPILOW Innovations improving welfare in low input and organic pig and poultry farms - Introducing the aWISH project: Animal Welfare indicators at the SlaughterHouse

Author: Collin, Anne, Maselyne, Jarissa, Biologie des Oiseaux et Aviculture (BOA), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Research Institute for Agricultural, Fisheries and Food (ILVO), European Commission - DG Agriculture and Rural Development, European Project: 816172,H2020-EU.3.2.1.1. - Increasing production efficiency and coping with climate change, while ensuring sustainability and resilience ,PPILOW (2019), and European Project: 101060818,aWISH
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience
Published: 2022

26. The Molecular Characterization of a New Prunus-Infecting Cheravirus and Complete Genome Sequence of Stocky Prune Virus

Author: Maryam Khalili, Thierry Candresse, Yoann Brans, Chantal Faure, Jean-Marc Audergon, Véronique Decroocq, Guillaume Roch, Armelle Marais, Biologie du fruit et pathologie (BFP), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Technique Interprofessionnel des Fruits et Légumes (CTIFL), Génétique et Amélioration des Fruits et Légumes (GAFL), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This study was funded by the European Union through the Horizon 2020 Marie Skłodow‐ska‐Curie Actions Innovative Training Network (H2020 MSCA‐ 60 ITN) project 'INEXTVIR' (Grant agreement number 813542). The plant indexing biological tests conducted by CTIFL were funded by INTERFEL (Fresh fruit and vegetable interprofessional association)., European Project: H2020 MSCA-60 ITN, and European Project: 813542,INEXTVIR
Subjects: prunus, Infectious Diseases, phylogenetic analysis, cheravirus, stocky prune virus, [SDV]Life Sciences [q-bio], Virology, high-throughput sequencing, stone fruit, alpine wild prunus virus, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy
Abstract: International audience; As part of a virome characterization of Prunus species, a novel cheravirus was discovered in two wild species, Prunus brigantina and P. mahaleb, and in an apricot (P. armeniaca) accession. The sequence of the two genomic RNAs was completed for two isolates. The Pro-Pol conserved region showed 86% amino acid (aa) identity with the corresponding region of trillium govanianum cheravirus (TgCV), a tentative Cheravirus member, whereas the combined coat proteins (CPs) shared only 40% aa identity with TgCV CPs, well below the species demarcation threshold for the genus. This suggests that the new virus should be considered a new species for which the name alpine wild prunus virus (AWPV) is proposed. In parallel, the complete genome sequence of stocky prune virus (StPV), a poorly known cheravirus for which only partial sequences were available, was determined. A phylogenetic analysis showed that AWPV, TgCV and StPV form a distinct cluster, away from other cheraviruses.
Published: 2022
Full Text: View/download PDF

27. Interactions of cholesterol molecules with GPCRs in different states: A comparative analysis of GPCRs' structures

Author: Christophe J. Moreau, Guillaume Audic, Laura Lemel, M. Dolores García-Fernández, Katarzyna Nieścierowicz, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-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), European Project: EST-16-66, and European Project: 682286,H2020,ERC-2015-CoG,NANOZ-ONIC(2016)
Subjects: Database, Cholesterol, Interaction, Protein/lipid, [SDV]Life Sciences [q-bio], Biophysics, Cell Biology, Structures, Biochemistry, GPCRs
Abstract: International audience
Published: 2022
Full Text: View/download PDF

28. Reconstructing long-term dengue virus immunity in French Polynesia

Author: Takahiro Nemoto, Maite Aubry, Yoann Teissier, Richard Paul, Van-Mai Cao-Lormeau, Henrik Salje, Simon Cauchemez, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Kyoto University, Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD), Direction de la Santé [Papeete], Génétique fonctionnelle des maladies infectieuses - Functional Genetics of Infectious Diseases, Pasteur Kyoto International Joint Research Unit for Integrative Vaccinomics [Kyoto, Japan], Institut Pasteur [Paris] (IP), University of Cambridge [UK] (CAM), This work was supported by the Investissement d’Avenir program, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program (grant ANR-10-LABX-62-IBEID https://anr.fr/ProjetIA-10-LABX-0062 to SC and HS), the European Research Council (No. 804744 https://cordis.europa.eu/project/id/804744 to SC and HS), and the European Commission Seventh Framework Program [FP7/2007-2013] (DENFREE project No.282378 https://cordis.europa.eu/project/id/282378 to RP and VMCL)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 804744,H2020-EU.1.1.,ARBODYNAMIC(2019), European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), Nemoto, Takahiro [0000-0003-2981-4035], and Apollo - University of Cambridge Repository
Subjects: Islands, Medicine and health sciences, Biology and life sciences, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, Immunity, French Polynesia, Dengue Virus, Dengue fever, Serogroup, Antibodies, Polynesia, Dengue, Medical risk factors, Earth sciences, Infectious Diseases, Serology, Seroepidemiologic Studies, Humans, People and places, Child, Research Article
Abstract: Funder: FP7 Ideas: European Research Council; funder-id: http://dx.doi.org/10.13039/100011199; Grant(s): 282378, BACKGROUND: Understanding the underlying risk of infection by dengue virus from surveillance systems is complicated due to the complex nature of the disease. In particular, the probability of becoming severely sick is driven by serotype-specific infection histories as well as age; however, this has rarely been quantified. Island communities that have periodic outbreaks dominated by single serotypes provide an opportunity to disentangle the competing role of serotype, age and changes in surveillance systems in characterising disease risk. METHODOLOGY: We develop mathematical models to analyse 35 years of dengue surveillance (1979-2014) and seroprevalence studies from French Polynesia. We estimate the annual force of infection, serotype-specific reporting probabilities and changes in surveillance capabilities using the annual age and serotype-specific distribution of dengue. PRINCIPAL FINDINGS: Eight dengue epidemics occurred between 1979 and 2014, with reporting probabilities for DENV-1 primary infections increasing from 3% to 5%. The reporting probability for DENV-1 secondary infections was 3.6 times that for primary infections. We also observed heterogeneity in reporting probabilities by serotype, with DENV-3 having the highest probability of being detected. Reporting probabilities declined with age after 14 y.o. Between 1979 and 2014, the proportion never infected declined from 70% to 23% while the proportion infected at least twice increased from 4.5% to 45%. By 2014, almost half of the population had acquired heterotypic immunity. The probability of an epidemic increased sharply with the estimated fraction of susceptibles among children. CONCLUSION/SIGNIFICANCE: By analysing 35 years of dengue data in French Polynesia, we characterised key factors affecting the dissemination profile and reporting of dengue cases in an epidemiological context simplified by mono-serotypic circulation. Our analysis provides key estimates that can inform the study of dengue in more complex settings where the co-circulation of multiple serotypes can greatly complicate inference.
Published: 2022
Full Text: View/download PDF

29. Persistent organic pollutant exposure and thyroid function among 12-year-old children

Author: Hélène Tillaut, Christine Monfort, Frank Giton, Charline Warembourg, Florence Rouget, Sylvaine Cordier, Fabrice Lainé, Eric Gaudreau, Ronan Garlantézec, Dave Saint-Amour, Cécile Chevrier, 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 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), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Santé Publique du Québec [Canada] (INSPQ), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Inserm, French Ministries of Health, French National Institute for Public Health Surveillance, National Agency for Research (ANR), French Agency for Environmental Health Safety (Afsset/ANSES), French Agency for Drug Safety, Fondation de France, French Ministry of Ecology (PNRPE), Research Institute of Public Health (IResP), European program Hi-WATE, European program ENRIECO, European program OBERON, French network of doctoral programs by EHESP French School of Public Health, ANR-14-CE21-0005,PELAGIE12,Etude de la croissance, de l'obésité, du développement pubertaire et des troubles neurocomportementaux chez les enfants à 12 ans, en association avec les expositions précoces à des polluants: la cohorte mère-enfant PELAGIE(2014), European Project: 226285,EC:FP7:ENV,FP7-ENV-2008-1,ENRIECO(2009), and European Project: 825712,H2020-EU.3.1.1. - Understanding health, wellbeing and disease,H2020-SC1-2018-Single-Stage-RTD,OBERON(2019)
Subjects: Cellular and Molecular Neuroscience, Endocrinology, Endocrine and Autonomic Systems, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, General Earth and Planetary Sciences, General Environmental Science
Abstract: International audience; IntroductionPolychlorobiphenyls (PCBs), organochlorine pesticides (OCPs) and per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants (POPs) having numerous toxicological properties, including thyroid endocrine disruption. Our aim was to assess the impact of POPs on thyroid hormones among 12-years children, while taking puberty into consideration MethodsExposure to 7 PCBs, 4 OCPs and 6 PFASs (in mu g/L), and free triiodothyronine (fT3, pg/mL), free thyroxine (fT4, ng/dL) and thyroid-stimulating hormones (TSH, mIU/L) were assessed through blood-serum measurements at age 12 in 249 boys and 227 girls of the PELAGIE mother-child cohort (France). Pubertal status was clinically rated using the Tanner stages. For each POP, associations were estimated using linear regression, adjusted for potential confounders.ResultsAmong boys, hexachlorobenzene and perfluorodecanoic acid were associated with decreased fT3 (log-scale; beta (95% Confidence Interval) =-0.07 (-0.12,-0.02) and beta=-0.03 (-0.06,-0.00) respectively). Intermediate levels of perfluorohexanesulfonic acid (PFHxS) and PCB180 were associated, respectively, with increased and decreased fT4. After stratification on pubertal status, PCBs and OCPs were associated with decreased TSH only in the more advanced Tanner stages (3, 4 and 5) and with decreased fT3 among early Tanner stages (1-2).Among girls, PFHxS was associated with decreased TSH (log-scale; beta=-0.15 (-0.29,-0.00)), and perfluorooctanoic acid was associated with decreased fT3 (beta 2nd_tercile=-0.06 (-0.10,-0.03) and beta 3rd_tercile=-0.04 (-0.08,-0.00), vs 1st tercile). Discussion / ConclusionThis cross-sectional study highlights associations between some POPs and thyroid function disruption, which appears consistent with the literature. Considering that the associations were sex-specific and moderated by pubertal status in boys, complex endocrine interactions are likely involved.
Published: 2022
Full Text: View/download PDF

30. Controlling Superselectivity of Multivalent Interactions with Cofactors and Competitors

Author: Tine Curk, Galina V. Dubacheva, Alain R. Brisson, Ralf P. Richter, Northwestern University [Evanston], Département de Chimie Moléculaire - Ingéniérie et Intéractions BioMoléculaires (DCM - I2BM), Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Leeds, Marie Skłodowska-Curie Fellowship 'ELNANO' (845032) to T.C., Marie Curie Career Integration Grant 'CELLMULTIVINT' (293803) to G.V.D., and European Research Council Starting Grant 'JELLY' (306435) and Biotechnology and Biological Sciences Research Council grant BB/T001631/1 to R.P.R., European Project: 306435,EC:FP7:ERC,ERC-2012-StG_20111012,JELLY(2012), and European Project: 293803,EC:FP7:PEOPLE,FP7-PEOPLE-2011-CIG,CELLMULTIVINT(2012)
Subjects: [PHYS]Physics [physics], Colloid and Surface Chemistry, [SDV]Life Sciences [q-bio], [CHIM]Chemical Sciences, Oligosaccharides, Receptors, Cell Surface, General Chemistry, Annexin A5, Hyaluronic Acid, Ligands, Biochemistry, Lipids, Catalysis
Abstract: International audience; Moieties that compete with multivalent interactions or act as cofactors are common in living systems, but their effect on multivalent binding remains poorly understood. We derive a theoretical model that shows how the superselectivity of multivalent interactions is modulated by the presence of cofactors or competitors. We find that the role of these participating moieties can be fully captured by a simple rescaling of the affinity constant of the individual ligand–receptor bonds. Theoretical predictions are supported by experimental data of the membrane repair protein annexin A5 binding to anionic lipid membranes in the presence of Ca2+ cofactors and of the extracellular matrix polysaccharide hyaluronan (HA) binding to CD44 cell surface receptors in the presence of HA oligosaccharide competitors. The obtained findings should facilitate understanding of multivalent recognition in biological systems and open new routes for fine-tuning the selectivity of multivalent nanoprobes in medicinal chemistry.
Published: 2022
Full Text: View/download PDF

31. Viscoelastic properties of suspended cells measured with shear flow deformation cytometry

Author: Richard Gerum, Elham Mirzahossein, Mar Eroles, Jennifer Elsterer, Astrid Mainka, Andreas Bauer, Selina Sonntag, Alexander Winterl, Johannes Bartl, Lena Fischer, Shada Abuhattum, Ruchi Goswami, Salvatore Girardo, Jochen Guck, Stefan Schrüfer, Nadine Ströhlein, Mojtaba Nosratlo, Harald Herrmann, Dorothea Schultheis, Felix Rico, Sebastian Müller, Stephan Gekle, Ben Fabry, Biophysics Group Friedrich-Alexander University, Van der Waals-Zeeman Institute, University of Amsterdam [Amsterdam] (UvA), Adhésion et Inflammation (LAI), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Max Planck Institute for the Science of Light, Max-Planck-Gesellschaft, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Universitätsklinikum Erlangen [Erlangen], University Hospital Erlangen = Uniklinikum Erlangen, Deutsche Forschungsgemeinschaft TRR-SFB 225 subprojects A01 Elham MirzahosseinHorizon 2020 No 812772 Mar ErolesHorizon 2020 No 953121 Mar Eroles Deutsche Forschungsgemeinschaft B07 Stephan GekleDeutsche Forschungsgemeinschaft A07 Stefan Schruefer, European Project: 812772,Phys2BioMed, and European Project: 953121
Subjects: General Immunology and Microbiology, Viscosity, [SDV]Life Sciences [q-bio], ddc:570, General Neuroscience, Stress, Mechanical, General Medicine, Flow Cytometry, Rheology, Elasticity, General Biochemistry, Genetics and Molecular Biology
Abstract: Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher level cellular functions in health and disease. We present a high-throughput, simple and low-cost microfluidic method for quantitatively measuring the elastic (storage) and viscous (loss) modulus of individual cells. Cells are suspended in a high-viscosity fluid and are pumped with high pressure through a 5.8 cm long and 200 µm wide microfluidic channel. The fluid shear stress induces large, ear ellipsoidal cell deformations. In addition, the flow profile in the channel causes the cells to rotate in a tank-treading manner. From the cell deformation and tank treading frequency, we extract the frequency-dependent viscoelastic cell properties based on a theoretical framework developed by R. Roscoe [1] that describes the deformation of a viscoelastic sphere in a viscous fluid under steady laminar flow. We confirm the accuracy of the method using atomic force microscopy-calibrated polyacrylamide beads and cells. Our measurements demonstrate that suspended cells exhibit power-law, soft glassy rheological behavior that is cell-cycle-dependent and mediated by the physical interplay between the actin filament and intermediate filament networks.Cells in the human body are viscoelastic: they have some of the properties of an elastic solid, like rubber, as well as properties of a viscous fluid, like oil. To carry out mechanical tasks – such as, migrating through tissues to heal a wound or to fight inflammation – cells need the right balance of viscosity and elasticity. Measuring these two properties can therefore help researchers to understand important cell tasks and how they are impacted by disease. However, quantifying these viscous and elastic properties is tricky, as both depend on the time-scale they are measured: when pressed slowly, cells appear soft and liquid, but they turn hard and thick when rapidly pressed. Here, Gerum et al. have developed a new system for measuring the viscosity and elasticity of individual cells that is fast, simple, and inexpensive. In this new method, cells are suspended in a specialized solution with a consistency similar to machine oil which is then pushed with high pressure through channels less than half a millimeter wide. The resulting flow of fluid shears the cells, causing them to elongate and rotate, which is captured using a fast camera that takes 500 images per second. Gerum et al. then used artificial intelligence to extract each cell’s shape and rotation speed from these images, and calculated their viscosity and elasticity based on existing theories of how viscoelastic objects behave in fluids. Gerum et al. also investigated how the elasticity and viscosity of cells changed with higher rotation frequencies, which corresponds to shorter time-scales. This revealed that while higher frequencies made the cells appear more viscous and elastic, the ratio between these two properties remained the same. This means that researchers can compare results obtained from different experimental techniques, even if the measurements were carried out at completely different frequencies or time-scales. The method developed by Gerum et al. provides a fast an inexpensive way for analyzing the viscosity and elasticity of cells. It could also be a useful tool for screening the effects of drugs, or as a diagnostic tool to detect diseases that affect the mechanical properties of cells.
Published: 2022
Full Text: View/download PDF

32. Therapeutic Assay with the Non-toxic C-Terminal Fragment of Tetanus Toxin (TTC) in Transgenic Murine Models of Prion Disease

Author: Inmaculada Martín-Burriel, Óscar López-Pérez, Juan José Badiola, Marina Betancor, Alicia Otero, Laura Moreno-Martínez, Rosa Bolea, Rosario Osta, Adelaida Hernaiz, Tomás Barrio, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, Instituto de Investigación Sanitaria de Aragón [Zaragoza] (IIS Aragón), Instituto Agroalimentario de Aragón (IA2), University of Zaragoza - Universidad de Zaragoza [Zaragoza]-Centro de Investigación y Tecnología Agroalimentaria de Aragón (CITA), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Open Access funding provided thanks to the CRUE‐CSIC agreement with Springer Nature. The project has been 65% cofinanced by the European Regional Development Fund (ERDF) through the Interreg V-A Spain-France-Andorra programme (POCTEFA 2014–2020). POCTEFA aims to reinforce the economic and social integration of the French–Spanish–Andorran border. Its support is focused on developing economic, social and environmental cross-border activities through joint strategies favouring sustainable territorial development., European Project: ERDF, European Project: EFA282/13, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, Genetically modified mouse, Male, Prion diseases, Transgene, [SDV]Life Sciences [q-bio], animal diseases, Neuroscience (miscellaneous), Scrapie, Mice, Transgenic, Pilot Projects, Biology, Neuroprotection, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Toxina tetànica, Mice, 0302 clinical medicine, Autofàgia, medicine, Autophagy, Animals, Amyotrophic lateral sclerosis, Neurodegeneration, Sheep, Brain, medicine.disease, 3. Good health, nervous system diseases, Tetanus toxin, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Neurology, Trk receptor, Cancer research, Prion, Female, Malalties per prions, 030217 neurology & neurosurgery
Abstract: The non-toxic C-terminal fragment of the tetanus toxin (TTC) has been described as a neuroprotective molecule since it binds to Trk receptors and activates Trk-dependent signaling, activating neuronal survival pathways and inhibiting apoptosis. Previous in vivo studies have demonstrated the ability of this molecule to increase mice survival, inhibit apoptosis and regulate autophagy in murine models of neurodegenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Prion diseases are fatal neurodegenerative disorders in which the main pathogenic event is the conversion of the cellular prion protein (PrPC) into an abnormal and misfolded isoform known as PrPSc. These diseases share different pathological features with other neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson’s disease or Alzheimer’s disease. Hitherto, there are no effective therapies to treat prion diseases. Here, we present a pilot study to test the therapeutic potential of TTC to treat prion diseases. C57BL6 wild-type mice and the transgenic mice Tg338, which overexpress PrPC, were intracerebrally inoculated with scrapie prions and then subjected to a treatment consisting of repeated intramuscular injections of TTC. Our results indicate that TTC displays neuroprotective effects in the murine models of prion disease reducing apoptosis, regulating autophagy and therefore increasing neuronal survival, although TTC did not increase survival time in these models.
Published: 2021
Full Text: View/download PDF

33. Optimization of oviposition trap settings to monitor populations of Aedes mosquitoes, vectors of arboviruses in La Reunion

Author: Ronan Brouazin, Iris Claudel, Renaud Lancelot, Guillaume Dupuy, Louis-Clément Gouagna, Marlène Dupraz, Thierry Baldet, Jérémy Bouyer, 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), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Agence Régionale de Santé La Réunion (ARS La Réunion), This research work was partially funded by the European Union, (i) European Research Council, Grant Agreement No. 682387-REVOLINC, and (ii) Horizon 2020 program, Grant Agreement No. 874850-MOOD, both in the framework of the One Health Indian Ocean partnership network ( www.onehealth-oi.org ). It is cataloged as MOOD-048., European Project: 682387,REVOLINC, and European Project: 874850
Subjects: [SDV]Life Sciences [q-bio], Oviposition, Mosquito Vectors, monitoring techniques [EN], Système de surveillance, Aedes aegypti, Aedes, Animals, Surveillance épidémiologique, Multidisciplinary, Lutte anti-insecte, arboviruses [EN], Piège, Aedes albopictus, Plant Breeding, Vecteur de maladie, Female, Reunion, Plastics, L72 - Organismes nuisibles des animaux, Ponte, Piégeage des animaux, Arboviruses
Abstract: Several dengue epidemics recently occurred in La Reunion, an island harboring two dengue viruses (DVs) vectors: Aedes albopictus, and Ae. aegypti, the former being the main local DV vector. Aedes aegypti shows a peculiar ecology, compared to other tropical populations of the same species. This study aimed to provide researchers and public-health users with locally validated oviposition traps (ovitraps) to monitor Aedes populations. A field experiment was performed in Saint-Joseph to assess the effect of different settings on the detection probability and apparent density of Aedes mosquitoes. Black plastic ovitraps were identified as the best choice. Vacoa trees (Pandanus utilis) were the only observed breeding sites for Ae. aegypti, shared with Ae. albopictus. They were the experimental units in a Latin square design with three factors: trap position in the trees (ground vs canopy), oviposition surface in the trap (blotting paper vs. vacoa leaf), and addition of organic matter to the trap water. The latter factor was found unimportant. On the ground, Ae. aegypti eggs were only found with vacoa leaves as the oviposition surface. Their detection and apparent density increased when ovitraps were located in the tree canopy. The main factor for Ae. albopictus was the oviposition surface, with a preference for blotting paper. In all trap settings, their detection was close to 100%. Larval survival was lower for a high egg density, combined with blotting paper as the oviposition surface. When monitoring mixed Aedes populations in La Reunion, we recommend using black plastic ovitraps, placed at 1.50-to-2.00-m high in vacoa trees, with vacoa leaves as the oviposition surface.
Published: 2022
Full Text: View/download PDF

34. Fit to dwell in many places – The growing diversity of intracellular Salmonella niches

Author: Chak Hon Luk, Jost Enninga, Camila Valenzuela, Dynamique des Interactions Hôte-Pathogène - Dynamics of Host-Pathogen Interactions, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The Francis Crick Institute [London], CHL is part of the Pasteur - Paris University (PPU) International PhD Program. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 665807. CHL is a recipient of the Doctoral Fellowship from the Croucher Foundation and 4th year Doctoral Award from Fondation pour la Recherche Médicale. JE acknowledges the support from the European Union (ERC-CG-grant: EndoSubvert), and the ANR (program: HBPSensing and PureMagRupture). JE is part of the IBEID and the Milieu Interieur LabExes., ANR-17-CE15-0006,HBPsensing,Mécanisme de détection de l'heptose 1,7-bisphosphate lors d'infections bactériennes à Gram négatif(2017), ANR-21-CE35-0007,PureMagRupture,Un flux de travail de la gMEP (Genetic magnetic-extraction-proteomics) pour comprendre le lien entre la rupture vacuolaire de Shigella et l'autophagie(2021), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), and European Project: 682809,EndoSubvert(2017)
Subjects: Microbiology (medical), host cell, Infectious Diseases, Salmonella, fibroblasts, [SDV]Life Sciences [q-bio], Immunology, host-pathogen interactions, Microbiology, epithelial cells, macrophages
Abstract: Salmonella enterica is capable of invading different host cell types including epithelial cells and M cells during local infection, and immune cells and fibroblasts during the subsequent systemic spread. The intracellular lifestyles of Salmonella inside different cell types are remarkable for their distinct residential niches, and their varying replication rates. To study this, researchers have employed different cell models, such as various epithelial cells, immune cells, and fibroblasts. In epithelial cells, S. Typhimurium dwells within modified endolysosomes or gains access to the host cytoplasm. In the cytoplasm, the pathogen is exposed to the host autophagy machinery or poised for rapid multiplication, whereas it grows at a slower rate or remains dormant within the endomembrane-bound compartments. The swift bimodal lifestyle is not observed in fibroblasts and immune cells, and it emerges that these cells handle intracellular S. Typhimurium through different clearance machineries. Moreover, in these cell types S. Typhimurium grows withing modified phagosomes of distinct functional composition by adopting targeted molecular countermeasures. The preference for one or the other intracellular niche and the diverse cell type-specific Salmonella lifestyles are determined by the complex interactions between a myriad of bacterial effectors and host factors. It is important to understand how this communication is differentially regulated dependent on the host cell type and on the distinct intracellular growth rate. To support the efforts in deciphering Salmonella invasion across the different infection models, we provide a systematic comparison of the findings yielded from cell culture models. We also outline the future directions towards a better understanding of these differential Salmonella intracellular lifestyles.
Published: 2022
Full Text: View/download PDF

35. Earbox, an open tool for high-throughput measurement of the spatial organization of maize ears and inference of novel traits

Author: V. Oury, T. Leroux, O. Turc, R. Chapuis, C. Palaffre, F. Tardieu, S. Alvarez Prado, C. Welcker, S. Lacube, Phymea Systems, Écophysiologie des Plantes sous Stress environnementaux (LEPSE), 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), Domaine expérimental de Melgueil (MONTP MELGUEIL UE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité expérimentale du maïs (BORDX ST-MARTIN UE), Instituto de Investigaciones Fisiologicas y Ecologicas Vinculadas a la Agricultura (IFEVA), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Agronomía [Buenos Aires], Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA), Universidad de Buenos Aires [Buenos Aires] (UBA), This study is a joined effort from Phymea-Systems and the INRAe. For Phymea-Systems, the work was largely financed by the company’s own resources with a participation from Région Occitanie funds. For the INRAe participation, this work was supported by the EU project FP7-244374 (DROPS), the projects ANR-10-BTBR-0001 (Amaizing) and ANR-11-INBS-0012 (Phenome) and the EU project H2020 731013 (EPPN2020)., ANR-10-BTBR-0001,AMAIZING,Développer de nouvelles variétés de maïs pour une agriculture durable: une approche intégrée de la génomique à la sélection(2010), ANR-11-INBS-0012,PHENOME,Centre français de phénomique végétale(2011), European Project: 244374,EC:FP7:KBBE,FP7-KBBE-2009-3,DROPS(2010), and European Project: 731013 ,EPPN2020(2017)
Subjects: Maize ear imaging, Grain abortion, [SDV]Life Sciences [q-bio], Genetics, Plant Science, CNN-based deep learning, Zea mays, Environmental response, Maize ear spatial organization, Biotechnology, Grain set
Abstract: Background Characterizing plant genetic resources and their response to the environment through accurate measurement of relevant traits is crucial to genetics and breeding. Spatial organization of the maize ear provides insights into the response of grain yield to environmental conditions. Current automated methods for phenotyping the maize ear do not capture these spatial features. Results We developed EARBOX, a low-cost, open-source system for automated phenotyping of maize ears. EARBOX integrates open-source technologies for both software and hardware that facilitate its deployment and improvement for specific research questions. The imaging platform consists of a customized box in which ears are repeatedly imaged as they rotate via motorized rollers. With deep learning based on convolutional neural networks, the image analysis algorithm uses a two-step procedure: ear-specific grain masks are first created and subsequently used to extract a range of trait data per ear, including ear shape and dimensions, the number of grains and their spatial organisation, and the distribution of grain dimensions along the ear. The reliability of each trait was validated against ground-truth data from manual measurements. Moreover, EARBOX derives novel traits, inaccessible through conventional methods, especially the distribution of grain dimensions along grain cohorts, relevant for ear morphogenesis, and the distribution of abortion frequency along the ear, relevant for plant response to stress, especially soil water deficit. Conclusions The proposed system provides robust and accurate measurements of maize ear traits including spatial features. Future developments include grain type and colour categorisation. This method opens avenues for high-throughput genetic or functional studies in the context of plant adaptation to a changing environment.
Published: 2022
Full Text: View/download PDF

36. Optimization of adult mosquito trap settings to monitor populations of Aedes and Culex mosquitoes, vectors of arboviruses in La Reunion

Author: Iris Claudel, Ronan Brouazin, Renaud Lancelot, Louis-Clément Gouagna, Marlène Dupraz, Thierry Baldet, Jérémy Bouyer, 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), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This research work was partially funded by the European Union, (i) European Research Council, Grant Agreement No. 682387-REVOLINC, and (ii) Horizon 2020 program, Grant Agreement No. 874850-MOOD, both in the framework of the One Health Indian Ocean partnership network (www.onehealth-oi.org). It is cataloged as MOOD044., European Project: 682387,REVOLINC, and European Project: 874850
Subjects: Male, Mosquito Control, [SDV]Life Sciences [q-bio], Mosquito Vectors, Méthode de lutte, Aedes aegypti, Aedes, Animals, Multidisciplinary, Lutte anti-insecte, Culex quinquefasciatus, Carbon Dioxide, Piège, Aedes albopictus, Culex, Vecteur de maladie, Female, Reunion, L72 - Organismes nuisibles des animaux, Arboviruses
Abstract: Competent arbovirus vectors are found in the culicid mosquito fauna of south-west Indian Ocean (SWIO) islands. In La Reunion, Aedes albopictus and Aedes aegypti mosquitoes are known vectors of dengue and chikungunya viruses. Culex quinquefasciatus is a potential vector of Rift Valley fever and West Nile viruses. To prepare a vector-control field trial against Ae. aegypti, this study aimed at identifying the best trapping strategy to catch adult Ae. aegypti, using BG-Sentinel traps (Biogents, Germany). It was implemented in two sites in southern La Reunion. Catches of Ae. albopictus and Cx. quinquefasciatus mosquitoes were also recorded. A Latin square design was used to estimate the detection probability and the apparent daily density—according to the BG-Sentinel trapping strategy: none, carbon dioxide (CO2), a commercial attractant—BG-Lure (Biogents, Germany), or both. The use of CO2 alone was associated with a higher detection probability for Ae. aegypti and Cx. quinquefasciatus mosquitoes, as well as a large increase in their apparent density. Traps with BG-Lure—alone or in combination with CO2, did not improve the detection probability of Ae. aegypti and Cx. quinquefasciatus mosquitoes. The same result was found for male Ae. albopictus. For females, baiting BG-Sentinel traps with CO2 or BG-Lure had no significant effect. The same apparent densities were found for Ae. aegypti and Ae. albopictus mosquitoes in both study sites—where Ae. aegypti mosquitoes were found at very low densities during previous surveys.
Published: 2022
Full Text: View/download PDF

37. With increasing site quality asymmetric competition and mortality reduces Scots pine (Pinus sylvestris L.) stand structuring across Europe

Author: Hans Pretzsch, Andrés Bravo-Oviedo, Torben Hilmers, Ricardo Ruiz-Peinado, Lluís Coll, Magnus Löf, Shamim Ahmed, Jorge Aldea, Christian Ammer, Admir Avdagić, Ignacio Barbeito, Kamil Bielak, Felipe Bravo, Gediminas Brazaitis, Jakub Cerný, Catherine Collet, Lars Drössler, Marek Fabrika, Michael Heym, Stig-Olof Holm, Gro Hylen, Aris Jansons, Viktor Kurylyak, Fabio Lombardi, Bratislav Matović, Marek Metslaid, Renzo Motta, Thomas Nord-Larsen, Arne Nothdurft, Cristóbal Ordóñez, Jan den Ouden, Maciej Pach, Marta Pardos, Quentin Ponette, Tomas Pérot, Ditlev Otto Juel Reventlow, Roman Sitko, Vit Sramek, Mathias Steckel, Miroslav Svoboda, Enno Uhl, Kris Verheyen, Sonja Vospernik, Barbara Wolff, Tzvetan Zlatanov, Miren del Río, UCL - SST/ELI/ELIE - Environmental Sciences, European Commission, German Research Foundation, Bavarian State Ministry for Nutrition, Agriculture and Forestry, Junta de Castilla y León, Universidad de Valladolid, Estonian Research Council, National Agency of Agricultural Research (Czech Republic), Slovak Research and Development Agency, Technische Universität München = Technical University of Munich (TUM), National Museum of Natural Sciences, Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Centro de Investigaciones Biológicas (CSIC), Universitat de Lleida, Swedish University of Agricultural Sciences (SLU), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Georg-August-University = Georg-August-Universität Göttingen, UNIVERSITY OF SARAJEVO - UNIVERZITET U SARAJEVU, University of British Columbia (UBC), Warsaw University of Life Sciences (SGGW), Sustainable Forest Management Research Institute, Universitad de Valladolid, Universidad de Valladolid [Valladolid] (UVa), Vytautas Magnus University - Vytauto Didziojo Universitetas (VDU), SILVA (SILVA), AgroParisTech-Université de Lorraine (UL)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Southern Swedish Forest Research Centre, Dept Forest Management & Geodesy, Fac Forestry, Technical University in Zvolen (TUZVO), Bayerische Landesanstalt für Wald und Forstwirtschaft - Bavarian State Institute of Forestry (LWF), European Project: 778322,H2020-EU.1.3.3.,CARE4C (2018), and European Project: 952314 ,Twinning of research institutions,ASFORCLIC (2021)
Subjects: Agriculture and Food Sciences, Skogsvetenskap, Monitoring, [SDV]Life Sciences [q-bio], Growth dominance coefficient, Structural heterogeneity, Management, Monitoring, Policy and Law, Boscos--Gestió, Asymmetry of competition, Gini coefficient, Tree mortality, Trastorns del creixement, Stuctural heterogeneity, ddc:630, Bosecologie en Bosbeheer, Asimetria (Química), Size-dependent mortality, Nature and Landscape Conservation, Diversity, Policy and Law, Forest Science, Mode of competitionGrowth dominance coefficient, Forestry, PE&RC, Forest Ecology and Forest Management, ddc, Management, Mode of competition, Gradient
Abstract: Heterogeneity of structure can increase mechanical stability, stress resistance and resilience, biodiversity and many other functions and services of forest stands. That is why many silvicultural measures aim at enhancing structural diversity. However, the effectiveness and potential of structuring may depend on the site conditions. Here, we revealed how the stand structure is determined by site quality and results from site-dependent partitioning of growth and mortality among the trees. We based our study on 90 mature, even-aged, fully stocked monocultures of Scots pine (Pinus sylvestris L.) sampled in 21 countries along a productivity gradient across Europe. A mini-simulation study further analyzed the site-dependency of the interplay between growth and mortality and the resulting stand structure. The overarching hypothesis was that the stand structure changes with site quality and results from the site-dependent asymmetry of competition and mortality. First, we show that Scots pine stands structure across Europe become more homogeneous with increasing site quality. The coefficient of variation and Gini coefficient of stem diameter and tree height continuously decreased, whereas Stand Density Index and stand basal area increased with site index. Second, we reveal a site-dependency of the growth distribution among the trees and the mortality. With increasing site index, the asymmetry of both competition and growth distribution increased and suggested, at first glance, an increase in stand heterogeneity. However, with increasing site index, mortality eliminates mainly small instead of all-sized trees, cancels the size variation and reduces the structural heterogeneity.Third, we modelled the site-dependent interplay between growth partitioning and mortality. By scenario runs for different site conditions, we can show how the site-dependent structure at the stand level emerges from the asymmetric competition and mortality at the tree level and how the interplay changes with increasing site quality across Europe. Our most interesting finding was that the growth partitioning became more asymmetric and structuring with increasing site quality, but that the mortality eliminated predominantly small trees, reduced their size variation and thus reversed the impact of site quality on the structure. Finally, the reverse effects of mode of growth partitioning and mortality on the stand structure resulted in the highest size variation on poor sites and decreased structural heterogeneity with increasing site quality. Since our results indicate where heterogeneous structures need silviculture interventions and where they emerge naturally, we conclude that these findings may improve system understanding and modelling and guide forest management aiming at structurally rich forests., This study was supported by the ERA-Net COFUND programme SUMFOREST, with the national funding organization Federal Ministry of Nutrition and Agriculture (REFORM, grant #2816ERA02S). The project has also received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No952314 and under the Marie Skłodowska-Curie grant agreement No 778322, and the 2017 - 2018 Belmont Forum and BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND programme, with the national funding organization Federal Ministry of Education and Research (grant #16LC1805B). The German Science Foundation funded the project “Structure and growth of mixed Scots pine/European beech stands compared with pure stands analyzed along an ecological gradient through Europe” (grant #PR 292/15-1). H.P. and E.U. were additionally supported by the Bavarian Ministry of Nutrition, Agriculture and Forestry through the projects “Pine-spruce mixed stands in Bavaria” (grant #7831-20339-2012) and “Maintenance of the long term experimental plots in Bavaria (W07, #7831-26625-2017). M.d.R. and R.R.-P. were supported by the projects CLU-2019-01 - iuFOR Institute Unit of Excellence” of the University of Valladolid and VA183P20–SMART, funded by the Junta de Castilla and Leon (Spain) and co-financed by the European Union (ERDF “Europe drives our growth”). J.C. was supported by the National Agency of Agricultural Research (Project No. QK21020307). K.B. was supported by the Polish Government MNiSW 2018–2021 Matching Fund No. 117/H2020/2018. M.M. was supported by the Estonian Research Council grant (PRG1586) and Estonian University of Life Sciences projects number P180024MIME and P200029MIME. R.S. was supported by the Slovak Research and Development Agency project No. APVV- 19-0035.
Published: 2022
Full Text: View/download PDF

38. Selection of study endpoints and patients for clinical trials in primary Sjögren's syndrome

Author: Suzanne Arends, Liseth de Wolff, Liselotte Deroo, Gwenny M. Verstappen, Arjan Vissink, Frans G.M. Kroese, Dirk Elewaut, Isabelle Peene, Hendrika Bootsma, University of Groningen [Groningen], Projet NECESSITY (PN), Hôpitaux Universitaires Paris Sud [AP-HP] (HUPS)-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-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University Medical Center Groningen [Groningen] (UMCG), Universiteit Gent = Ghent University (UGENT), Ghent University Hospital, The RESULT cohort was supported by the Dutch Arthritis Society (15-1-303), unrestricted research grants from Bristol-Myers Squibb (NCT02067910) and Novartis, Horizon 2020 (HarmonicSS proposal 731944, Necessity IMI-2 proposal 806975). ERN member ReCONNET., European Project: 806975,NECESSITY, European Project: 731944 ,HarmonicSS, Translational Immunology Groningen (TRIGR), and Personalized Healthcare Technology (PHT)
Subjects: clinical trials, inclusion criteria, treatment, Rheumatology, study endpoints, [SDV]Life Sciences [q-bio], Immunology, Immunology and Allergy, Sjögren's syndrome
Abstract: International audience; In the last decade, many randomised controlled trials (RCTs) with biological DMARDs (bDMARDs) have been performed in patients with primary Sjögren's syndrome (pSS). Unfortunately, no bDMARD has yet been approved for systemic treatment of pSS. The heterogeneity of disease manifestations raises two essential questions: 1) which outcome measure is valid, reliable and responsive to demonstrate treatment efficacy and should be used as primary study endpoint? and 2) which pSS patients should be included in clinical trials? Both the selection of the primary study endpoint and the selection of patients are crucial and evolving issues in clinical trial design in pSS. This article summarises the history and comments the selection of primary study endpoints including the novel development of composite endpoints. Furthermore, this article gives an overview of inclusion criteria used for phase II and III trials, and illustrates by data-analysis based on two prospective observational cohorts that each additional selection criterion will (largely) decrease the number of eligible patients in daily clinical practice.
Published: 2022
Full Text: View/download PDF

39. Enhanced nanofluidic transport in activated carbon nanoconduits

Author: Theo Emmerich, Kalangi S. Vasu, Antoine Niguès, Ashok Keerthi, Boya Radha, Alessandro Siria, Lydéric Bocquet, Micromegas : Nano-Fluidique, Laboratoire de physique de l'ENS - ENS Paris (LPENS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), University of Manchester [Manchester], ANR-17-CE09-0046,NEPTUNE,Transport hors equilibre de fluides aux échelles nanométriques(2017), European Project: 785911,Shadoks, and European Project: 637748,H2020,ERC-2014-STG,NanoSOFT(2015)
Subjects: Theory and computation, [PHYS]Physics [physics], Ion Transport, Two-dimensional Materials, Mechanical Engineering, [SDV]Life Sciences [q-bio], MESH: Graphite, Biological Transport, General Chemistry, Condensed Matter Physics, Nanostructures, MESH: Charcoal, MESH: Ion Transport, MESH: Nanostructures, Fluid dynamics, Mechanics of Materials, Charcoal, MESH: Biological transport, Graphite, General Materials Science
Abstract: Carbon has emerged as a unique material in nanofluidics, with reports of fast water transport, molecular ion separation and efficient osmotic energy conversion. Many of these phenomena still await proper rationalization due to the lack of fundamental understanding of nanoscale ionic transport, which can only be achieved in controlled environments. Here we develop the fabrication of 'activated' two-dimensional carbon nanochannels. Compared with nanoconduits with 'pristine' graphite walls, this enables the investigation of nanoscale ionic transport in great detail. We show that activated carbon nanochannels outperform pristine channels by orders of magnitude in terms of surface electrification, ionic conductance, streaming current and (epi-)osmotic currents. A detailed theoretical framework enables us to attribute the enhanced ionic transport across activated carbon nanochannels to an optimal combination of high surface charge and low friction. Furthermore, this demonstrates the unique potential of activated carbon for energy harvesting from salinity gradients with single-pore power density across activated carbon nanochannels, reaching hundreds of kilowatts per square metre, surpassing alternative nanomaterials.
Published: 2022
Full Text: View/download PDF

40. A genomic amplification affecting a carboxylesterase gene cluster confers organophosphate resistance in the mosquito Aedes aegypti: From genomic characterization to high‐throughput field detection

Author: Jean-Marc Bonneville, Frederic Laporte, Ian W. Sutherland, Benedicte Fustec, Jeffrey C. Hertz, Tristan Cumer, Sébastien Marcombe, Julien Renaud, Thierry Gaude, Jean-Philippe David, Sébastien Boyer, Camille Noûs, Victor Arnaud, Chloé Haberkorn, Julien Cattel, Laboratoire d'Ecologie Alpine (LECA ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Naval Air Station Jacksonville (NAS Jacksonville), United States Navy - U.S. Navy (USA), Naval Medical Research Unit Two [Singapore] (NAMRU-2), Naval Medical Research, Khon Kaen University [Thailand] (KKU), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur du Laos, This work was conducted in the framework of the U.S. Naval Medical Research Unit TWO projects BIO‐LAO‐2 (work unit number D1425) and ARBOVEC‐PLUS (work unit number D1428), in support and funded by the Department of Defense Global Emerging Infections Surveillance Program and Military Infectious Disease Research Program. I (IWS and JCH) am a military Service member. This work was prepared as part of my official duties. Title 17, U.S.C., Section 105 provides that copyright protection under this title is not available for any work of the U.S. Government. Title 17, U.S.C., Section 101 defines a U.S. Government work as a work prepared by a military Service member or employee of the U.S. Government as part of that person's official duties. This publication was also supported by the project, Research Infrastructures for the control of vector‐borne diseases (Infravec2), which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 731060. Dr. Julien Cattel was supported by funding from the European Union's Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement no. 734548. The field study in Cambodia was supported by ECOMORE 2 project, coordinated by Institut Pasteur and financially supported by AFD (Agence Française pour le Développement)., European Project: 731060,INFRAVEC2(2017), European Project: 734548,ZIKAlliance(2016), United States Navy Entomology, Laboratoire Cogitamus, Laboratoire d'Ecologie Alpine (LECA), and Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])
Subjects: 0106 biological sciences, 0301 basic medicine, Evolution, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Population, Locus (genetics), mosquito, Aedes aegypti, Biology, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, diagnostic assay, Gene cluster, Gene duplication, Genetics, QH359-425, Multiplex, Copy-number variation, education, Gene, ComputingMilieux_MISCELLANEOUS, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Whole genome sequencing, 0303 health sciences, education.field_of_study, Haplotype, Original Articles, insecticide resistance, carboxylesterase, biology.organism_classification, 030104 developmental biology, [SDE]Environmental Sciences, genomic amplification, Original Article, General Agricultural and Biological Sciences
Abstract: By altering gene expression and creating paralogs, genomic amplifications represent a key component of short-term adaptive processes. In insects, the use of insecticides can select gene amplifications causing an increased expression of detoxification enzymes, supporting the usefulness of these DNA markers for monitoring the dynamics of resistance alleles in the field. In this context, the present study aims to characterise a genomic amplification event associated with resistance to organophosphate insecticides in the mosquito Aedes aegypti and to develop a molecular assay to monitor the associated resistance alleles in the field. An experimental evolution experiment using a composite population from Laos supported the association between the over-transcription of multiple contiguous carboxylesterase genes on chromosome 2 and resistance to multiple organophosphate insecticides. Combining whole genome sequencing and qPCR on specific genes confirmed the presence of a ~100 Kb amplification spanning at least five carboxylesterase genes at this locus with the co-existence of multiple structural duplication haplotypes. Field data confirmed their circulation in South-East Asia and revealed high copy number polymorphism among and within populations suggesting a trade-off between this resistance mechanism and associated fitness costs. A dual-colour multiplex TaqMan assay allowing the rapid detection and copy number quantification of this amplification event in Ae. aegypti was developed and validated on field populations. The routine use of this novel assay will improve the tracking of resistance alleles in this major arbovirus vector.
Published: 2021
Full Text: View/download PDF

41. In silico comparative study of SARS-CoV-2 proteins and antigenic proteins in BCG, OPV, MMR and other vaccines: evidence of a possible putative protective effect

Author: Houcemeddine Othman, Imen Ben Mustapha, Maher Kharrat, Kais Ghedira, Henda Triki, Rabeb Touati, Sondes Haddad-Boubaker, Kaouther Ayouni, Marwa Lakhal, Laboratoire de Virologie Clinique, Référence Régional OMS pour la Poliomyélite et la Rougeole - Laboratory of Clinical Virology, WHO Regional Reference Laboratory on Poliomyelitis and Measles, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université de Tunis El Manar (UTM), Virus, Vecteurs et Hôtes [Tunis], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), University of the Witwatersrand [Johannesburg] (WITS), Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Laboratoire de Bioinformatique, biomathématiques, biostatistiques (BIMS) (LR11IPT09), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Tunis El Manar (UTM), This study was funded by the Tunisian Ministry of Higher Education and Scientific Research (Research laboratory: Virus, Vectors and Hosts, LR20IPT10). It was also partially supported by the European project PHINDaccess: Strengthening Omics data analysis capacities in pathogen-host interaction (Grant Agreement ID: 811034)., and European Project: 811034,H2020-EU.4.b.,PHINDaccess(2018)
Subjects: Protein Conformation, Cross Protection, [SDV]Life Sciences [q-bio], OPV, Biochemistry, 0302 clinical medicine, MESH: Protein Conformation, Structural Biology, MESH: COVID-19, BCG, 030212 general & internal medicine, Antigens, Viral, lcsh:QH301-705.5, 0303 health sciences, Tetanus, Applied Mathematics, Viral Vaccine, Immunogenicity, Hepatitis B, MMR, Computer Science Applications, 3. Good health, MESH: BCG Vaccine, MESH: COVID-19 Vaccines, BCG Vaccine, lcsh:R858-859.7, MESH: Antigens, Viral, Research Article, Antigenicity, COVID-19 Vaccines, In silico, Putative protection, Biology, lcsh:Computer applications to medicine. Medical informatics, Measles, 03 medical and health sciences, Viral Proteins, Antigen, MESH: Computer Simulation, MESH: Viral Vaccines, medicine, Humans, Computer Simulation, MESH: SARS-CoV-2, Molecular Biology, 030304 developmental biology, MESH: Humans, SARS-CoV-2, COVID-19, Viral Vaccines, medicine.disease, Virology, MESH: Viral Proteins, MESH: Cross Protection, lcsh:Biology (General), Vaccine
Abstract: Background Coronavirus Disease 2019 (COVID-19) is a viral pandemic disease that may induce severe pneumonia in humans. In this paper, we investigated the putative implication of 12 vaccines, including BCG, OPV and MMR in the protection against COVID-19. Sequences of the main antigenic proteins in the investigated vaccines and SARS-CoV-2 proteins were compared to identify similar patterns. The immunogenic effect of identified segments was, then, assessed using a combination of structural and antigenicity prediction tools. Results A total of 14 highly similar segments were identified in the investigated vaccines. Structural and antigenicity prediction analysis showed that, among the identified patterns, three segments in Hepatitis B, Tetanus, and Measles proteins presented antigenic properties that can induce putative protective effect against COVID-19. Conclusions Our results suggest a possible protective effect of HBV, Tetanus and Measles vaccines against COVID-19, which may explain the variation of the disease severity among regions.
Published: 2021
Full Text: View/download PDF

42. Polyphenolic compounds of Phyllanthus amarus Schum & Thonn. (1827) and diabetes-related activity of an aqueous extract as affected by in vitro gastrointestinal digestion

Author: Mélissa Matou, Patrick Merciris, Mayra Luz Sanchez-Villavicencio, Gaëtan Herbette, Remi Neviere, Pierre Haddad, Thérèse Marianne-Pepin, Sylvie Bercion, UNIVERSITE DES ANTILLES, Université de Montréal (UdeM), Université Aix Marseille, CHUM, Université des Antilles (UA), Region Guadeloupe 009/CDR/2016, European Project: 32525, European Project: 32755, and European Project: OP2-144645
Subjects: Pharmacology, [SDV]Life Sciences [q-bio], Drug Discovery, [CHIM]Chemical Sciences, Phyllanthus amarus Enriched polysaccharides fraction In vitro gastrointestinal digestion UHPLC-HRMS Glucose uptake Glucose-6-phosphatase
Abstract: International audience; Ethnopharmacological relevanceExtracts of the aerial part of Phyllanthus amarus have been extensively used in several countries to cure diabetes. No data is available on the impact of gastrointestinal digestion of such crude extracts on their antidiabetic activity.Aim of the studyThe aim of this study was to identify active fractions and compounds of fresh aerial parts of P. amarus extracted by an infusion method that are responsible for antidiabetic effects occurring at the level of glucose homeostasis.Materials and methodsAn aqueous extract was obtained by an infusion method and its polyphenolic composition was analysed by reverse phase UPLC-DAD-MS. The influence of in vitro gastrointestinal digestion was evaluated both on the chemical composition and on the antidiabetic effect of P. amarus infusion extract using glucose-6-phosphatase enzyme inhibition and stimulation of glucose uptake.ResultsAnalysis of the chemical composition of the crude extract revealed the presence of polysaccharides and various families of polyphenols such as phenolic acids, tannins, flavonoids and lignans. After simulated digestion, the total content of polyphenols decreased by about 95%. Caffeoylglucaric acid derivates and lignans exhibited strong stimulation of glucose uptake similar to metformin with an increase of 35.62 ± 6.14% and 34.74 ± 5.33% respectively. Moreover, corilagin, geraniin, the enriched polysaccharides fraction and the bioaccessible fraction showed strong anti-hyperglycemic activity with about 39–62% of glucose-6-phosphatase inhibition.ConclusionCaffeoylglucaric acid isomers, tannin acalyphidin M1 and lignan demethyleneniranthin were reported for the first time in the species. After in vitro gastroinstestinal digestion, the composition of the extract changed. The dialyzed fraction showed strong glucose-6-phosphatase inhibition.; Intérêt ethnopharmacologiqueLes extraits de la partie aérienne de Phyllanthus amarus ont été largement utilisés dans plusieurs pays pour soigner le diabète. Aucune donnée n'est disponible sur l'impact de la digestion gastro-intestinale de ces extraits bruts sur leur activité antidiabétique.Objectif de l'étudeLe but de cette étude était d'identifier les fractions actives et les composés des parties aériennes fraîches de P. amarus extraites par infusion aqueuse qui sont responsables des effets antidiabétiques au niveau de l'homéostasie du glucose.Matériels et méthodesUn extrait aqueux a été obtenu par une méthode d'infusion et sa composition polyphénolique a été analysée par UPLC-DAD-MS en phase inverse. L'influence de la digestion gastro-intestinale in vitro a été évaluée à la fois sur la composition chimique et sur l'effet antidiabétique de l'extrait d'infusion de P. amarus en utilisant l'inhibition de l'enzyme glucose-6-phosphatase et la stimulation de l'absorption du glucose.RésultatsL'analyse de la composition chimique de l'extrait brut a révélé la présence de polysaccharides et de diverses familles de polyphénols tels que les acides phénoliques, les tanins, les flavonoïdes et les lignanes. Après une digestion simulée, la teneur totale en polyphénols a diminué d'environ 95 %. Les dérivés de l'acide caféoyl glucarique et les lignanes ont montré une forte stimulation de l'absorption du glucose similaire à la metformine avec une augmentation de 35,62 ± 6,14% et 34,74 ± 5,33% respectivement. De plus, la corilagine, la géraniine, la fraction enrichie en polysaccharides et la fraction bioaccessible ont montré une forte activité anti-hyperglycémique avec environ 39-62% d'inhibition de la glucose-6-phosphatase.ConclusionLes isomères de l'acide caféoyl glucarique, le tanin acalyphidine M1 et le lignane déméthyléneranthine ont été rapportés pour la première fois dans l'espèce. Après une digestion gastro-intestinale in vitro, la composition de l'extrait a changé. La fraction dialysée a montré une forte inhibition de la glucose-6-phosphatase.
Published: 2023
Full Text: View/download PDF

43. Genome-wide macroevolutionary signatures of key innovations in butterflies colonizing new host plants

Author: Fabien L. Condamine, Rémi Allio, Adam M. Cotton, Guillaume Chomicki, Benoit Nabholz, Gael J. Kergoat, Felix A. H. Sperling, Anne-Laure Clamens, Stefan Wanke, Oscar Alejandro Pérez-Escobar, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Institut für Botanik [Dresden], Durham University, Royal Botanic Gardens [Kew], Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), University of Alberta, This project has received funding from the Marie Curie International Outgoing Fellow under the European Union's Seventh Framework Programme (project BIOMME, agreement no. 627684), a PICS grant from the CNRS (project PASTA), an 'Investissement d'Avenir' grant from the Agence Nationale de la Recherche (project CASMA, CEBA, ref. ANR-10-LABX-0025) and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (project GAIA, agreement no. 851188) to F.L.C., a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (RGPIN-2018-04920) to F.A.H.S., and a German Research Foundation grant (WA 2461/9-1) to S.W., ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), European Project: 627684,EC:FP7:PEOPLE,FP7-PEOPLE-2013-IOF,BIOMME(2015), European Project: 851188,GAIA, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Duke University [Durham], Royal Botanic Gardens, Kew, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0106 biological sciences, 0301 basic medicine, Time Factors, [SDV]Life Sciences [q-bio], Science, Genome, Insect, General Physics and Astronomy, Diversification (marketing strategy), Biology, Evolutionary ecology, 010603 evolutionary biology, 01 natural sciences, Genome, Article, General Biochemistry, Genetics and Molecular Biology, Beringia, Host-Parasite Interactions, Evolution, Molecular, 03 medical and health sciences, Species Specificity, Phylogenetics, Molecular evolution, Genetic algorithm, Animals, Host plants, Ecosystem, Phylogeny, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Geography, fungi, food and beverages, Biodiversity, General Chemistry, Plants, 15. Life on land, 030104 developmental biology, Biogeography, Evolutionary biology, Adaptation, Butterflies, Genome-Wide Association Study
Abstract: The mega-diversity of herbivorous insects is attributed to their co-evolutionary associations with plants. Despite abundant studies on insect-plant interactions, we do not know whether host-plant shifts have impacted both genomic adaptation and species diversification over geological times. We show that the antagonistic insect-plant interaction between swallowtail butterflies and the highly toxic birthworts began 55 million years ago in Beringia, followed by several major ancient host-plant shifts. This evolutionary framework provides a valuable opportunity for repeated tests of genomic signatures of macroevolutionary changes and estimation of diversification rates across their phylogeny. We find that host-plant shifts in butterflies are associated with both genome-wide adaptive molecular evolution (more genes under positive selection) and repeated bursts of speciation rates, contributing to an increase in global diversification through time. Our study links ecological changes, genome-wide adaptations and macroevolutionary consequences, lending support to the importance of ecological interactions as evolutionary drivers over long time periods., Arms races between herbivores and plants have likely affected their evolutionary histories, which could have led to their high diversity. Allio et al. find that butterflies shifting to new host plants have more adaptive molecular signatures across their genomes and show repeated bursts of speciation rates.
Published: 2021
Full Text: View/download PDF

44. A case study to dissect immunity to SARS-CoV-2 in a neonate nonhuman primate model

Author: Claire-Maëlle Fovet, Camille Pimienta, Mathilde Galhaut, Francis Relouzat, Natalia Nunez, Mariangela Cavarelli, Quentin Sconosciuti, Nina Dhooge, Ilaria Marzinotto, Vito Lampasona, Monica Tolazzi, Gabriella Scarlatti, Raphaël Ho Tsong Fang, Thibaut Naninck, Nathalie Dereuddre-Bosquet, Jérôme Van Wassenhove, Anne-Sophie Gallouët, Pauline Maisonnasse, Roger Le Grand, Elisabeth Menu, Nabila Seddiki, Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, 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, Life and Soft, IRCCS Ospedale San Raffaele [Milan, Italy], Mucosal Immunity and Sexually Transmitted Infection Control (MISTIC), Institut Pasteur [Paris] (IP), The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT’s facilities and imaging technologies. The NHP model of SARS-CoV-2 infection have been developed thanks to the support from REACTing, the Fondation pour la Recherche Medicale (FRM, AM-CoV-Path) The virus stock used in NHPs was obtained even through the EVAg platform (https://www.european-virus-archive.com/), funded by H2020 (653316). The work performed at IRCCS Ospedale San Raffaele (OSR) was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (COVID-2020-12371617)., ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), ANR-10-EQPX-0002,FlowCyTech,Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales(2010), European Project: 730964, H2020, RIA,H2020-INFRAIA-2016-1,TRANSVAC2(2017), European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), MENU, Elisabeth, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, Equipements d'excellence - Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales - - FlowCyTech2010 - ANR-10-EQPX-0002 - EQPX - VALID, European Vaccine Research and Development Infrastructure - TRANSVAC2 - - H2020, RIA2017-05-01 - 2022-04-30 - 730964 - VALID, and European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID
Subjects: Primates, [SDV]Life Sciences [q-bio], Immunology, Pilot Projects, nonhuman primate, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, children, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, microbiota, Animals, Humans, Immunology and Allergy, Child, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, innate immunity, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, type-I IFN, SARS-CoV-2, Infant, Newborn, COVID-19, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV] Life Sciences [q-bio], pediatric, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cytokines, RNA, Viral, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, neonate
Abstract: International audience; Most children are less severely affected by coronavirus-induced disease 2019 (COVID-19) than adults, and thus more difficult to study progressively. Here, we provide a neonatal nonhuman primate (NHP) deep analysis of early immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in blood and mucosal tissues. In addition, we provide a comparison with SARS-CoV-2-infected adult NHP. Infection of the neonate resulted in a mild disease compared with adult NHPs that develop, in most cases, moderate lung lesions. In concomitance with the viral RNA load increase, we observed the development of an early innate response in the blood, as demonstrated by RNA sequencing, flow cytometry, and cytokine longitudinal data analyses. This response included the presence of an antiviral type-I IFN gene signature, a persistent and lasting NKT cell population, a balanced peripheral and mucosal IFN-γ/IL-10 cytokine response, and an increase in B cells that was accompanied with anti-SARS-CoV-2 antibody response. Viral kinetics and immune responses coincided with changes in the microbiota profile composition in the pharyngeal and rectal mucosae. In the mother, viral RNA loads were close to the quantification limit, despite the very close contact with SARS-CoV-2-exposed neonate. This pilot study demonstrates that neonatal NHPs are a relevant model for pediatric SARS-CoV-2 infection, permitting insights into the early steps of anti-SARS-CoV-2 immune responses in infants.
Published: 2022
Full Text: View/download PDF

45. Comorbidities in the UK Primary Sjögren’s Syndrome Registry

Author: Jessica Tarn, Dennis Lendrem, Michael Barnes, John Casement, Wan-Fai Ng, Newcastle University [Newcastle], Projet NECESSITY (PN), Hôpitaux Universitaires Paris Sud [AP-HP] (HUPS)-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-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Queen Mary University of London (QMUL), Newcastle Upon Tyne Hospitals NHS Foundation Trust, This work was supported by Foundation of Research in Rheumatology (FOREUM): (grant number: 022). This work received infrastructure support from the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre and the NIHR Clinical Research Facility, based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and from the Arthritis Research UK and Versus Arthritis Newcastle upon Tyne Experimental Arthritis Treatment Centre. The UKPSSR received grant support from the UK Medical Research Council (grant number G0800629 to W-FN, SJB, BG) and British Sjögren’s Syndrome Association. This work was supported, in part, by the National Institute for Health Research: NIHR202635 - Artificial Intelligence Multimorbidity Development Award and the Innovative Medicines Initiative 2 Joint Undertaking (JU) (NECESSITY grant agreement No 806975) receiving support from the European Union’s Horizon 2020 research and innovation program and EFPIA., European Project: 806975,NECESSITY, European Project: (grant No 116060),IMPRiND, Piatrova, Alena, NEw Clinical Endpoints in primary Sjögren’s Syndrome: an Interventional Trial based on stratifYing patients - NECESSITY - 0000-00-00 - 0000-00-00 - 806975 - VALID, and EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking. - IMPRiND - (grant No 116060) - INCOMING
Subjects: [SDV]Life Sciences [q-bio], Immunology, stratified medicine, Pain, crossectional analysis, United Kingdom, [SDV] Life Sciences [q-bio], comorbidity, Sjogren's syndrome, Humans, Immunology and Allergy, Registries, polypharmacy, Fatigue
Abstract: IntroductionPrimary Sjögren’s Syndrome (PSS) is a chronic disease characterised by symptoms of oral and ocular dryness, pain, fatigue, anxiety and depression. PSS patients can be subclassified by the pattern of severity of these five key symptoms using the Newcastle Sjögren’s Stratification Tool (NSST). Although PSS is often associated with one or more comorbidities, the relationship between comorbidities, polypharmacy, and PSS symptom burden is unclear. Using data from the UK Primary Sjögren’s Syndrome Registry (UKPSSR) we describe the landscape of polypharmacy and comorbidities in PSS.MethodsThe UKPSSR is research biobank of clinically well-defined PSS patients where clinical, demographic, comorbidities and concomitant medications data are recorded. Patients were subclassified into the four NSST subgroups: Low Symptom Burden (LSB), High Symptom Burden (HSB), Dryness Dominated Fatigue (DDF) and Pain Dominated Fatigue (PDF). Group analyses of comorbid conditions and polypharmacy scores were performed. Comorbidity and Polypharmacy Scores (CPS) were modelled as a function of age, sex, symptom duration, body mass index (BMI), current immunosuppressant and hydroxychloroquine prescriptions and NSST subgroup.ResultsThere were marked differences in the number and the nature of comorbidities associated with the NSST subgroups. LSB and DDF patients were characterized by fewer comorbidities and medications. In contrast, HSB and PDF patients were associated with more comorbidities and were more likely to be prescribed multiple medications. Group analysis shows that HSB patients are more closely associated with peripheral vascular disease and infection whereas the PDF patients were associated with cardiovascular disease and gastrointestinal comorbidities. Comorbidity and polypharmacy scores increase with age and BMI regardless of symptom subgroup and symptom duration. In addition, the longer the reported symptom duration the higher the associated comorbidities and polypharmacy scores.ConclusionComorbid conditions are more prevalent in some subgroups of the PSS cohort but increase with age and BMI across the entire cohort. It is unclear from these data whether specific comorbid conditions are a consequence of PSS or represent shared aetiology or pathogenetic susceptibility. Regardless, these findings may have implications for disease management and clinical trial design.
Published: 2022
Full Text: View/download PDF

46. Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis

Author: Noémie Lefrancq, Valérie Bouchez, Nadia Fernandes, Alex-Mikael Barkoff, Thijs Bosch, Tine Dalby, Thomas Åkerlund, Jessica Darenberg, Katerina Fabianova, Didrik F. Vestrheim, Norman K. Fry, Juan José González-López, Karolina Gullsby, Adele Habington, Qiushui He, David Litt, Helena Martini, Denis Piérard, Paola Stefanelli, Marc Stegger, Jana Zavadilova, Nathalie Armatys, Annie Landier, Sophie Guillot, Samuel L. Hong, Philippe Lemey, Julian Parkhill, Julie Toubiana, Simon Cauchemez, Henrik Salje, Sylvain Brisse, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Cambridge [UK] (CAM), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre national de Référence de la Coqueluche et autres Bordetelloses - National Reference Center for Whooping Cough and other Bordetella infections (CNR), University of Turku, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Statens Serum Institut [Copenhagen], The Public Health Agency of Sweden, National Institute of Public Health [Prague], Norwegian Institute of Public Health [Oslo] (NIPH), Public Health England [London], Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Uppsala University, Children's Health Ireland [Crumlin, Dublin, Ireland] (CHI), Vrije Universiteit Brussel (VUB), Istituto Superiore di Sanità (ISS), Rega Institute, 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), The study was supported financially by the French Government Investissement d’Avenir grant ANR-16-CONV-0005 (INCEPTION project, to S.B. and H.S.). The National Reference Center for Whooping Cough and Other Bordetella Infections receives support from Institut Pasteur and Public Health France (Santé publique France, Saint Maurice, France). This work was also supported financially by the French Government’s Investissement d’Avenir program Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID) to S.B. and a European Research Council (no. 804744 to H.S.). P.L. acknowledges funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 725422-ReservoirDOCS)., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 804744,H2020-EU.1.1.,ARBODYNAMIC(2019), European Project: 725422,ERC-2016-COG,ReservoirDOCS(2017), Supporting clinical sciences, Microbiology and Infection Control, Clinical Biology, Lefrancq, Noémie [0000-0001-5991-6169], Bouchez, Valérie [0000-0002-5947-6383], Fernandes, Nadia [0000-0003-4595-9939], Dalby, Tine [0000-0003-4774-7091], Åkerlund, Thomas [0000-0001-7516-0218], Darenberg, Jessica [0000-0002-8528-8570], Fabianova, Katerina [0000-0001-8374-4395], Fry, Norman K [0000-0003-4862-6507], González-López, Juan José [0000-0003-2419-5909], Gullsby, Karolina [0000-0002-9673-0483], Habington, Adele [0000-0001-6997-3327], Litt, David [0000-0002-9215-0553], Martini, Helena [0000-0002-5877-9948], Piérard, Denis [0000-0002-7756-3691], Stefanelli, Paola [0000-0003-1620-4385], Stegger, Marc [0000-0003-0321-1180], Armatys, Nathalie [0000-0003-2042-4241], Landier, Annie [0000-0002-8278-4026], Hong, Samuel L [0000-0001-6354-4943], Lemey, Philippe [0000-0003-2826-5353], Parkhill, Julian [0000-0002-7069-5958], Cauchemez, Simon [0000-0001-9186-4549], Salje, Henrik [0000-0003-3626-4254], Brisse, Sylvain [0000-0002-2516-2108], and Apollo - University of Cambridge Repository
Subjects: Europe, Pertussis Vaccine, Genotype, Whooping Cough, [SDV]Life Sciences [q-bio], Humans, General Medicine, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bordetella pertussis
Abstract: As with other pathogens, competitive interactions between Bordetella pertussis strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures; however, this has rarely been measured because of inadequate data and analytical tools. We used 3344 sequences from 23 countries to show that, on average, there are 28.1 transmission chains circulating within a subnational region, with the number of chains strongly associated with host population size. It took 5 to 10 years for B. pertussis to be homogeneously distributed throughout Europe, with the same time frame required for the United States. Increased fitness of pertactin-deficient strains after implementation of acellular vaccines, but reduced fitness otherwise, can explain long-term genotype dynamics. These findings highlight the role of vaccine policy in shifting local diversity of a pathogen that is responsible for 160,000 deaths annually.
Published: 2022
Full Text: View/download PDF

47. Force-generating apoptotic cells orchestrate avian neural tube bending

Author: Daniela Roellig, Sophie Theis, Amsha Proag, Guillaume Allio, Bertrand Bénazéraf, Jérôme Gros, Magali Suzanne, Unité de biologie moléculaire, cellulaire et du développement - UMR5077 (MCD), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Morphogénie Logiciels, Institut Pasteur [Paris] (IP), M.S.’s lab is supported by grants from the European Research Council (ERC) under the European Union Horizon 2020 research and innovation program (grant number EPAF: 648001), from the Institut National de la Santé et de la Recherche Médicale (Inserm, Plan cancer 2014–2019), and from the association Toulouse Cancer Santé (TCS, ApoMacImaging: 171441). S.T. had a CIFRE fellowship from the ANRT and now has a fellowship from the Fondation pour la Recherche Médicale (FRM). The transgenic quail lines used in this project were generated thanks to the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) and ERC grant agreement no: 337635 to J.G., We thank Eric Theveneau, Alice Davy, Corinne Benassayag, and Bruno Monier for their constructive comments on the manuscript., European Project: 648001,H2020,ERC-2014-CoG,EPAF(2015), and European Project: 337635,EC:FP7:ERC,ERC-2013-StG,LIMBCELLDYNAMICS(2014)
Subjects: quail/chicken, Neural Tube, [SDV]Life Sciences [q-bio], nucleus fragmentation, apoptosis, morphogenesis, neural tube closure, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Epithelium, epithelium folding, mechanical forces, Animals, Molecular Biology, Neurulation, Developmental Biology
Abstract: International audience; Apoptosis plays an important role in morphogenesis, and the notion that apoptotic cells can impact their surroundings came to light recently. However, how this applies to vertebrate morphogenesis remains unknown. Here, we use the formation of the neural tube to determine how apoptosis contributes to morphogenesis in vertebrates. Neural tube closure defects have been reported when apoptosis is impaired in vertebrates, although the cellular mechanisms involved are unknown. Using avian embryos, we found that apoptotic cells generate an apico-basal force before being extruded from the neuro-epithelium. This force, which relies on a contractile actomyosin cable that extends along the apico-basal axis of the cell, drives nuclear fragmentation and influences the neighboring tissue. Together with the morphological defects observed when apoptosis is prevented, these data strongly suggest that the neuroepithelium keeps track of the mechanical impact of apoptotic cells and that the apoptotic forces, cumulatively, contribute actively to neural tube bending.
Published: 2022
Full Text: View/download PDF

48. E-cadherin focuses protrusion formation at the front of migrating cells by impeding actin flow

Author: Cecilia Grimaldi, Jean-Christophe Olivo-Marin, Jan Schick, Jan Bandemer, Erez Raz, Aleix Boquet-Pujadas, Isabel Schumacher, Timo Betz, Anne Aalto, Bart Vos, Katsiaryna Tarbashevich, Zentrum für Molekularbiologie der Entzündung - Center for Molecular Biology of Inflammation [Münster, Germany] (ZMBE), Westfälische Wilhelms-Universität Münster (WWU), Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), This work was supported by the European Research Council (ERC, CellMig), the German Research Foundation (DFG, CRC 1348 and RA 863/11-1), The Medical Faculty of the University of Muenster and the Cells in Motion cluster. C.G. is a member of the CiM-IMPRS Graduate School. A.B.-P. is part of the Pasteur-Paris University (PPU) International PhD Programme, which received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 665807, and from the Institut Carnot Pasteur Microbes & Santé (ANR-16 CARN 0023-01). The BIA unit is partially supported by grants from the Labex IBEID (ANR-10-LABX-62-IBEID), France-BioImaging infrastructure (ANR-10-INBS-04), and the programme PIA INCEPTION (ANR-16-CONV-0005). T.B. and B.E.V. were supported by the European Research Council (Consolidator Grant 771201). Open Access funding enabled and organized by Projekt DEAL, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 268806,EC:FP7:ERC,ERC-2010-AdG_20100317,CELLMIG(2011), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Embryology, [SDV]Life Sciences [q-bio], Cell, General Physics and Astronomy, MESH: Actomyosin, MESH: Cadherins, 0302 clinical medicine, Cell Movement, Adherens junctions, MESH: Animals, Pseudopodia, lcsh:Science, MESH: Cell Movement, Zebrafish, Multidisciplinary, biology, Chemistry, Actomyosin, Adhesion, Cadherins, Cell biology, medicine.anatomical_structure, Female, Leading edge, Cell type, Science, MESH: Zebrafish Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Actins, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine, Animals, Cell migration, MESH: Zebrafish, Actin, Cadherin, Front (oceanography), General Chemistry, Zebrafish Proteins, biology.organism_classification, Actins, MESH: Male, MESH: Germ Cells, Germ Cells, 030104 developmental biology, MESH: Pseudopodia, lcsh:Q, MESH: Female, 030217 neurology & neurosurgery
Abstract: The migration of many cell types relies on the formation of actomyosin-dependent protrusions called blebs, but the mechanisms responsible for focusing this kind of protrusive activity to the cell front are largely unknown. Here, we employ zebrafish primordial germ cells (PGCs) as a model to study the role of cell-cell adhesion in bleb-driven single-cell migration in vivo. Utilizing a range of genetic, reverse genetic and mathematical tools, we define a previously unknown role for E-cadherin in confining bleb-type protrusions to the leading edge of the cell. We show that E-cadherin-mediated frictional forces impede the backwards flow of actomyosin-rich structures that define the domain where protrusions are preferentially generated. In this way, E-cadherin confines the bleb-forming region to a restricted area at the cell front and reinforces the front-rear axis of migrating cells. Accordingly, when E-cadherin activity is reduced, the bleb-forming area expands, thus compromising the directional persistence of the cells., The arrival of migratory cells at their targets relies on following precise routes within tissues. Here the authors demonstrate that the cell adhesion molecule E-cadherin can control the path of cell migration by confining the site where bleb-type protrusions form within the cell front.
Published: 2020
Full Text: View/download PDF

49. Impact of Uric Acid on Hypertension Occurrence and Target Organ Damage: Insights From the STANISLAS Cohort With a 20-Year Follow-up

Author: Jean-Loup Machu, Nicolas Girerd, Jean-Marc Boivin, Sandra Wagner, Patrick Rossignol, Faiez Zannad, Erwan Bozec, Mehmet Kanbay, Kevin Duarte, João Pedro Ferreira, Koç University, 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), 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), 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 ), The STANISLAS study is sponsored by the Nancy CHRU.This work is supported by the French Ministry of Health 'Programme Hospitalier de Recherche Clinique Inter regional 2013,' by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project 'Lorraine Université d’Excellence,' Reference ANR-15-IDEX-04-LUE. It is also supported by the European Fibro-Targets Project (grant agreement no. SP7#602904), European HOMAGE project (grant agreement no. Heart 'Omics' in Ageing, 7th Framework Program grant # 305507), the MEDIA project (Européen 'Cooperation'—Theme 'Health'/FP7-HEALTH- 2010-single-stage (reference: 261409), FOCUS-MR (reference:ANR-15-CE14-0032-01), ERA-CVD EXPERT (reference:ANR-16-ECVD-0002-02), and the Fondation de Recherche en Hypertension Artérielle., IMPACT GEENAGE, ANR-16-ECVD-0002,EXPERT,Exploring new pathways in age-related heart diseases(2016), ANR-15-CE14-0032,MR-focus,Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque(2015), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE (ISITE),Lorraine Université d'Excellence(2016), European Project: 261409,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,MEDIA(2011), European Project: 305507,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HOMAGE(2013), European Project: 602904,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,FIBRO-TARGETS(2013), DE CARVALHO, Philippe, Exploring new pathways in age-related heart diseases - - EXPERT2016 - ANR-16-ECVD-0002 - ERA-CVD - VALID, Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque - - MR-focus2015 - ANR-15-CE14-0032 - AAPG2015 - VALID, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, The MEtabolic Road to DIAstolic Heart Failure - MEDIA - - EC:FP7:HEALTH2011-01-01 - 2016-06-30 - 261409 - VALID, Heart OMics in AGEing - HOMAGE - - EC:FP7:HEALTH2013-02-01 - 2019-01-31 - 305507 - VALID, and Targeting cardiac fibrosis for heart failure treatment - FIBRO-TARGETS - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 602904 - VALID
Subjects: Male, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Left ventricular hypertrophy, Cohort Studies, Ventricular Dysfunction, Left, 0302 clinical medicine, Risk Factors, Longitudinal Studies, 030212 general & internal medicine, Hyperuricemia, Pulse wave velocity, 2. Zero hunger, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, blood pressure, Middle Aged, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, left ventricular hypertrophy, 3. Good health, [SDV] Life Sciences [q-bio], Creatinine, Cohort, Cardiology, Female, Hypertrophy, Left Ventricular, France, Glomerular Filtration Rate, Adult, medicine.medical_specialty, hypertension, End organ damage, pulse wave velocity, Population, Pulse Wave Analysis, albuminuria, 03 medical and health sciences, Vascular Stiffness, uric acid, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Internal Medicine, medicine, Humans, cardiovascular diseases, Renal Insufficiency, Chronic, education, Aged, business.industry, medicine.disease, Blood pressure, business, Body mass index, chronic kidney disease, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BACKGROUND Recent studies have shown that hyperuricemia may be associated with incident hypertension (HTN). We examined whether serum uric acid (SUA) is a predictor of HTN and target organ damage (TOD) 20 years later in initially healthy middle-aged individuals. METHODS Participants from the Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) a single-center familial longitudinal cohort study (961 initially healthy adults and 570 children) underwent clinical and laboratory measurements at baseline and after approximately 20 years. Blood pressure (BP: using ambulatory BP measurements), urine albumin-to-creatinine ratio, estimated glomerular filtration rate (eGFR), left ventricular hypertrophy (LVH), diastolic dysfunction, and carotid–femoral pulse wave velocity (PWV) were measured at the end of follow-up. RESULTS In the parent population, higher baseline or last SUA levels and higher change in SUA (ΔUA) were significantly associated with an increased risk of HTN development, even after adjusting for known HTN risk factors (all P < 0.01). Higher baseline SUA was marginally associated with an increased risk of having high carotid–femoral PWV (P = 0.05). The association of SUA with BP increase was body mass index dependent (the increase in BP being greater in leaner subjects; interactionp < 0.05), and the association of SUA with eGFR decline was age dependent (the decline in eGFR being greater in older subjects; interactionp < 0.05). There was no significant association between SUA and diastolic dysfunction or LVH. In the whole population (i.e. including children), a significant association between SUA at baseline and the risk of HTN and higher carotid–femoral PWV was also found (both P < 0.02). CONCLUSIONS Increased SUA is associated with the development of HTN and vascular/renal TOD in initially healthy midlife subjects.
Published: 2020
Full Text: View/download PDF

50. Les protéinopathies infectieuses de Parkinson et d’Alzheimer

Author: R. Melki, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), 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 Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ANR-17-JPCD-0002,TransPathND,Intraneuronal transport-related pathways across neurodegenerative diseases(2017), ANR-17-JPCD-0005,Protest-70,Protecting protein homeostasis in synucleinopathies and tauopathies by modulating the Hsp70/co-chaperone network(2017), European Project: (grant No 116060),IMPRiND, and European Project: 821522,PD-MitoQUANT - H2020-EU.3.1.7. - Innovative Medicines Initiative 2 (IMI2)
Subjects: 0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], General Medicine, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030217 neurology & neurosurgery, 3. Good health
Abstract: International audience; L’apparition de dépôts intra- ou extracellulaires de protéines dans le système nerveux central est le signe distinctif de plusieurs troubles neurodégénératifs progressifs chez l’homme. Les constituants protéiques de ces dépôts et les régions du cerveau touchées diffèrent d’un trouble neurodégénératif à un autre. Jusqu’à récemment, on pensait que le cercle vicieux constitué par l’agrégation de protéines, leur propagation/multiplication et l’accumulation dans le système nerveux central ce ces agrégats était l’apanage de la protéine prion PrP. De récentes données suggèrent que des agrégats de protéines constitués de protéines distinctes de la PrP se propagent et s’amplifient dans le système nerveux central, entraînant différentes maladies. La façon dont les agrégats de la protéine alpha-synucléine circulent entre les cellules, s’amplifient en recrutant de l’alpha-synucléine monomérique endogène et provoquent des synucléinopathies distinctes, n’est pas claire. Je passe en revue ici les preuves expérimentales à l’appui de la propagation des agrégats de l’alpha-synucléine à la manière des agrégats de la protéine prion PrP. Je décris également comment l’alpha-synucléine s’agrège. J’explique aussi comment l’agrégation de l’alpha-synucléine peut conduire à des synucléinopathies distinctes. Je conclus cette revue par une comparaison des propriétés de l’alpha-synucleine et de la protéine Tau dont l’agrégation est impliquée dans différentes tauopathies, dont la maladie d’Alzheimer.
Published: 2020
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

3,167 results on '"European Project"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources