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Cette contribution s’intéresse à l’impact de la pandémie de COVID-19 sur les Établissements et Services d’Aide par le Travail (ESAT) français à partir d’entretiens conduits auprès de directeurs d’établissements situés dans le milieu rural et urbain de la Région Auvergne-Rhône-Alpes (France). Afin de situer les ESAT dans leur contexte national, un premier temps est consacré à rappeler la genèse et le fonctionnement de ce dispositif, mis en place pour favoriser l’insertion sociale et professionnelle des travailleurs en situation de handicap, dont l’originalité réside dans l’articulation d’une logique médico-sociale à une logique économique. Nous cherchons ensuite à montrer comment les ESAT se sont organisés pour assurer l’accompagnement médico-social de leurs travailleurs malgré l’obligation de distanciation. Puis, analysé au prisme de l’ancrage territorial et de la notion de proximité qui lui est associée, nous nous intéressons à l’impact du confinement sur l’équilibre économique de ces établissements pour montrer que la crise sanitaire a moins affecté les établissements à vocation majoritairement agricole implantés en milieu rural que ceux, plus orientés vers la sous-traitance industrielle, localisés en milieu urbain. This contribution focuses on the impact of the COVID-19 pandemic on French support and work assistance establishment (ESAT) based on interviews conducted with managers of institutions located in rural and urban areas of the Auvergne-Rhône-Alpes region (France). In order to situate the ESAT in their national context, a first section is devoted to recalling the genesis and functioning of this system, which was set up to promote the social and occupational integration of workers with disabilities, whose originality lies in the articulation of a medico-social logic with an economical logic. We then try to show how the ESAT have organized themselves to provide medico-social support for workers with disabilities despite the obligation of distancing. Then, analyzed through the prism of territorial anchoring and the concept of proximity associated with it, we will focus on the impact of confinement on the economic balance of these establishments to show that the health crisis has less affected the establishments in predominantly agricultural vocation established in rural areas than those, more oriented towards industrial subcontracting, located in urban areas.

Daté 2020 mais paru en 2021; International audience; Cet article vise à revenir sur l'activité de Jean Rottner pendant la crise du coronavirus à partir d'une analyse détaillée de ses interventions durant cette période, qui font de lui un acteur bénéficiant d'une médiatisation importante sinon extraordinaire. Pour ce faire, l'article mobilise la notion de conjoncture critique. Il défend la thèse que c'est le gestionnaire hospitalier plus que le soignant qui agit de manière ajustée dans la crise, mais aussi l'élu local qui tente de consolider sa position. L'analyse se fonde sur un dépouillement de la presse nationale et régionale ainsi que sur d'autres sources complémentaires.

The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19. One sentence summary: The spread of COVID-19 in China was driven by human mobility early on and mitigated substantially by drastic control measures implemented since the end of January.

The binding of F4+ enterotoxigenic Escherichia coli (ETEC) and the specific receptor on porcine intestinal epithelial cells is the initial step in F4+ ETEC infection. Porcine aminopeptidase N (APN) is a newly discovered receptor for F4 fimbriae that binds directly to FaeG adhesin, which is the major subunit of the F4 fimbriae variants F4ab, F4ac, and F4ad. We used overlapping peptide assays to map the APN-FaeG binding sites, which has facilitated in the identifying the APN-binding amino acids that are located in the same region of FaeG variants, thereby limiting the major binding regions of APN to 13 peptides. To determine the core sequence motif, a panel of FaeG peptides with point mutations and FaeG mutants were constructed. Pull-down and binding reactivity assays using piglet intestines determined that the amino acids G159 of F4ab, N209 and L212 of F4ac, and A200 of F4ad were the critical residues for APN binding of FaeG. We further show using ELISA and confocal microscopy assay that amino acids 553–568, and 652–670 of the APN comprise the linear epitope for FaeG binding in all three F4 fimbriae variants. Electronic supplementary material The online version of this article (10.1186/s13567-018-0519-9) contains supplementary material, which is available to authorized users.

Turnip yellow mosaic virus (TYMV) - a member of the alphavirus-like supergroup of viruses - serves as a model system for positive-stranded RNA virus membrane-bound replication. TYMV encodes a precursor replication polyprotein that is processed by the endoproteolytic activity of its internal cysteine proteinase domain (PRO). We recently reported that PRO is actually a multifunctional enzyme with a specific ubiquitin hydrolase (DUB) activity that contributes to viral infectivity. Here, we report the crystal structure of the 150-residue PRO. Strikingly, PRO displays no homology to other processing proteinases from positive-stranded RNA viruses, including that of alphaviruses. Instead, the closest structural homologs of PRO are DUBs from the Ovarian tumor (OTU) family. In the crystal, one molecule's C-terminus inserts into the catalytic cleft of the next, providing a view of the N-terminal product complex in replication polyprotein processing. This allows us to locate the specificity determinants of PRO for its proteinase substrates. In addition to the catalytic cleft, at the exit of which the active site is unusually pared down and solvent-exposed, a key element in molecular recognition by PRO is a lobe N-terminal to the catalytic domain. Docking models and the activities of PRO and PRO mutants in a deubiquitylating assay suggest that this N-terminal lobe is also likely involved in PRO's DUB function. Our data thus establish that DUBs can evolve to specifically hydrolyze both iso- and endopeptide bonds with different sequences. This is achieved by the use of multiple specificity determinants, as recognition of substrate patches distant from the cleavage sites allows a relaxed specificity of PRO at the sites themselves. Our results thus shed light on how such a compact protein achieves a diversity of key functions in viral genome replication and host-pathogen interaction. Author Summary Positive-stranded RNA viruses are ultimate parasites. In order to replicate their genome, they first need to invade a host cell and, with usually very limited viral genetic material, subvert the host's molecular machinery. Turnip yellow mosaic virus (TYMV) is an excellent model system for studying positive-stranded RNA virus replication. As for many such viruses, TYMV genome replication is dependent on the activity of a viral proteinase (PRO) to properly process the virus' replication molecules. We have recently established that PRO is a multifunctional enzyme and is also used by TYMV to subvert a key host defense against pathogens. We report here the atomic structure of PRO as well as new functional data on PRO's interaction with the host. Our data shed light on how PRO can perform such multiple activities despite its small size, providing TYMV with a Swiss army knife in its ongoing fight with a vastly more complex host.

Les coronavirus sont une famille de virus qui infectent un grand nombre de mammifères et d’oiseaux. Cette famille de virus est connue pour sa capacité à franchir les barrières d’espèces et à en infecter de nouvelles. La pandémie actuelle de COVID-19 (coronavirus disease 19) est la conséquence de la troisième émergence de coronavirus, la plus récente, dans la population humaine depuis le début du siècle, celle du SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Les coronavirus sont des virus enveloppés à ARN simple brin de polarité positive, qui, comme tous les virus, exploitent la machinerie cellulaire pour se multiplier. À ce jour, il n’existe aucun vaccin ni traitement antiviral spécifique pour lutter contre les coronavirus, mais plusieurs pistes thérapeutiques sont explorées pour traiter le COVID-19.

Authors affiliations: (1) Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, Inserm, CNRS, Marseille, France (2) Ecole Normale Supérieure de Lyon, Université Claude Bernard – Lyon I, Université de Lyon, Lyon, France (3)Centre d'Immunophénomique, Aix Marseille Université , Inserm, CNRS, Marseille, France (4) TERI (Tumor Escape, Resistance and Immunity) Department, Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, Université Claude Bernard – Lyon 1, Université de Lyon, Inserm, CNRS, Lyon, France (5) Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA (6) Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China (7) University Paris-Saclay, Inserm U1015, Gustave Roussy Cancer Center, Villejuif, France (8) Singapore Immunology Network, A*STAR, Singapore, Singapore (9) Centre for Inflammation Biology and Cancer Immunology, Cancer Research UK King's Health Partners Centre, School of Immunology and Microbial Sciences, King's College London, London SE1 1UL, UK (10) Lead contact The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of tissue-resident MM in viral infection. MHC-II� MM were abundant neonatally, whereas MHC-II+ MM appeared over time. These barrier macrophages differentially responded to in vivo peripheral challenges such as LPS, SARS-CoV-2, and lymphocytic choriomeningitis virus (LCMV). Peripheral LCMV infection, which was asymptomatic, led to a transient infection and activation of the meninges. Mice lacking macrophages but conserving brain microglia, or mice bearing macrophage-specific deletion of Stat1 or Ifnar, exhibited extensive viral spread into the CNS. Transcranial pharmacological depletion strategies targeting MM locally resulted in several areas of the meninges becoming infected and fatal meningitis. Low numbers of MHC-II+ MM, which is seen upon LPS challenge or in neonates, corelated with higher viral load upon infection. Thus, MMs protect against viral infection and may present targets for therapeutic manipulation.

AbstractThe increased resolution of single-cell RNA-sequencing technologies has led to major breakthroughs and improved our understanding of the normal and pathologic conditions of multiple tissues and organs. In the study of parenchymal lung disease, single-cell RNA-sequencing has better delineated known cell populations and identified novel cells and changes in cellular phenotypes and gene expression patterns associated with disease. In this review, we aim to highlight the advances and insights that have been made possible by applying these technologies to two seemingly very different lung diseases: fibrotic interstitial lung diseases, a group of relentlessly progressive lung diseases leading to pulmonary fibrosis, and COVID-19 pneumonia, an acute viral disease with life-threatening complications, including pulmonary fibrosis. We discuss changes in cell populations and gene expression, highlighting potential common features, such as alveolar cell epithelial injury and aberrant repair and monocyte-derived macrophage populations, as well as relevance and implications to mechanisms of disease and future directions.

International audience; The year 2020 was characterised by a worldwide pandemic crisis due to dissemination of a Coronavirus, the SARS-CoV-2 also named COVID-19. Many economic and social domains were impacted by adaptions or restrictions by the objective to limit local dispersion and more global flow of the virus. Without describing all human health effects of this virus, one characteristic is temporary anosmia. In this paper, firstly the physiological impact is synthetized to explain the anosmia. Secondly, because olfactometry need human smell, adaptations of sensorial methods are described. These adapted methods were proposed by laboratories/companies in charge of olfactometry or odour measurement and mainly concern how the distance guarantees between panellists were proposed.