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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.

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.

For the last two decades, researchers have placed hopes in a new era in which a combination of reperfusion and neuroprotection would revolutionize the treatment of stroke. Nevertheless, despite the thousands of papers available in the literature showing positive results in preclinical stroke models, randomized clinical trials have failed to show efficacy. It seems clear now that the existing data obtained in preclinical research have depicted an incomplete picture of stroke pathophysiology. In order to ameliorate bench-to-bed translation, in this review we first describe the main actors on stroke inflammatory and immune responses based on the available preclinical data, highlighting the fact that the link between leukocyte infiltration, lesion volume and neurological outcome remains unclear. We then describe what is known on neuroinflammation and immune responses in stroke patients, and summarize the results of the clinical trials on immunomodulatory drugs. In order to understand the gap between clinical trials and preclinical results on stroke, we discuss in detail the experimental results that served as the basis for the summarized clinical trials on immunomodulatory drugs, focusing on (i) experimental stroke models, (ii) the timing and selection of outcome measuring, (iii) alternative entry routes for leukocytes into the ischemic region, and (iv) factors affecting stroke outcome such as gender differences, ageing, comorbidities like hypertension and diabetes, obesity, tobacco, alcohol consumption and previous infections like Covid-19. We can do better for stroke treatment, especially when targeting inflammation following stroke. We need to re-think the design of stroke experimental setups, notably by (i) using clinically relevant models of stroke, (ii) including both radiological and neurological outcomes, (iii) performing long-term follow-up studies, (iv) conducting large-scale preclinical stroke trials, and (v) including stroke comorbidities in preclinical research. Highlights • The different experimental approaches may model different aspects of stroke. • Drugs need to be tested in several clinically relevant experimental stroke models. • Clot composition, type of arterial occlusion and recanalization need to be considered. • Outcomes should include acute but also long-term measurements. • Both infarct volume and behavioral deficits need to be systematically measured. • Including coexisting risk factors in preclinical stroke research is mandatory. • Performing multicenter studies may increase the reliability of preclinical results.

International audience

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.

Bats carry a great diversity of zoonotic viruses with a high-impact on human health and livestock. Since the emergence of new coronaviruses and paramyxoviruses in humans (e.g. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Nipah virus), numerous studies clearly established that bats can maintain some of these viruses. Improving our understanding on the role of bats in the epidemiology of the pathogens they harbour is necessary to prevent cross-species spill over along the wild/domestic/human gradient. In this study, we screened bat faecal samples for the presence of Coronavirus and Paramyxovirus in two caves frequently visited by local people to collect manure and/or to hunt bats in Zimbabwe. We amplified partial RNA-dependent RNA polymerase genes of Alpha and Betacoronavirus together with the partial polymerase gene of Paramyxovirus. Identified coronaviruses were related to pathogenic human strains and the paramyxovirus belonged to the recently described Jeilongvirus genus. Our results highlighted the importance of monitoring virus circulation in wildlife, especially bats, in the context of intense human-wildlife interfaces in order to strengthen prevention measures among local populations and to implement sentinel surveillance in sites with high zoonotic diseases transmission potential. Highlights • Coronavirus and Paramyxovirus circulate in Hipposideros bat species in Zimbabwe. • Importance of widening viral screening in under-investigated countries • Sentinel surveillance in sites with high zoonotic transmission potential

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.

Even though much has been learned about the new pathogen SARS-CoV-2 since the beginning of the COVID-19 pandemic, a lot of uncertainty remains. In this paper we argue that what is important to know under uncertainty is whether harm accelerates and whether health policies achieve deceleration of harm. For this, we need to see cases in relation to diagnostic effort and not to look at indicators based on cases only, such as a number of widely used epidemiological indicators, including the reproduction number, do. To do so overlooks a crucial dimension, namely the fact that the best we can know about cases will depend on some welldefined strategy of diagnostic effort, such as testing in the case of COVID-19. We will present a newly developed indicator to observe harm, the acceleration index, which is essentially an elasticity of cases in relation to tests. We will discuss what efficiency of testing means and propose that the corresponding health policy goal should be to find ever fewer cases with an ever-greater diagnostic effort. Easy and low-threshold testing will also be a means to give back people’s sovereignty to lead their life in an “open” as opposed to “locked-down” society.