Les frontières de l'humour, application du sujet en cours de FLE

Ce TFM dresse un tableau de l'humour, de ses apports, ses limites, ses frontières. Dans une première partie, nous retraçons dans les grandes lignes son histoire en France, et nous tentons de définir ce vaste concept. L'humour a cela d’intéressant qu'il est à la fois universel et très marqué par la culture, il trouve donc parfaitement sa place en classe de FLE, car bien que pas toujours évident à traiter ou à transmettre, il aborde l'interculturalité, compétence essentielle dans l'acquisition d'une nouvelle langue. Ce TFM a aussi servi d'occasion pour présenter une personnalité marquante de la culture française, tant sociale qu'humoristique, Coluche. Enfin, nous détaillons les différents supports par lesquels peut s'exprimer l'humour ainsi que quelques recommandations sur son bon usage en cours et ses bénéfices. Ce TFM s'accompagne de quelques propositions d'activités qui mettent en pratique certains aspects évoqués.Este TFM traza un cuadro del humor, de sus aportaciones, sus límites, sus fronteras. En una primera parte, retratamos a grandes rasgos su historia en Francia, y tratamos de definir este vasto concepto. El humor tiene esto interesante que es a la vez universal y muy marcado por la cultura, por lo que encuentra perfectamente su lugar en clase de FLE, porque aunque no siempre es evidente a tratar o transmitir, aborda la interculturalidad, competencia esencial en la adquisición de un nuevo idioma. Este TFM sirvió también de ocasión para presentar una personalidad destacada de la cultura francesa, tanto social como humorística, Coluche. Por último, detallamos los diferentes soportes a través de los cuales se puede expresar el humor, así como algunas recomendaciones sobre su buen uso en clase y sus beneficios. Este TFM conlleva algunas propuestas didácticas que ponen en practica algunos de los aspectos tratados.Departamento de Filología Francesa y AlemanaMáster en Profesor de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idioma

Large scale screening discovers clofoctol as an inhibitor of SARS-CoV-2 replication that reduces COVID-19-like pathology

The fastest way to implement a treatment against a new rapidly emerging viral disease consists in screening the potential antiviral activity of drugs approved for human use. This has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against SARS-CoV-2 with relevant potency. Of the 1,942 compounds tested, 21 exhibited a substantial antiviral activity in Vero-81 cells. Among them, clofoctol, an antibacterial drug used for the treatment of bacterial respiratory tract infections, was further investigated due to its favorable safety profile and its pharmacokinetic properties. Notably, the peak concentration of clofoctol that can be achieved in human lungs is more than 20 times higher than its IC 95 measured against SARS-CoV-2 in human pulmonary cells. Mechanistically, this compound inhibits SARS-CoV-2 at a post-entry step by specifically blocking translation initiation of viral RNA. Lastly, therapeutic treatment of human ACE2 receptor transgenic mice decreased viral load, reduced inflammatory gene expression and improved pulmonary pathology. Altogether, these data strongly support clofoctol as a therapeutic candidate for the treatment of COVID-19 patients

Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice

International audienceDrug repurposing has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against SARS-CoV-2 with relevant potency. Of the 1,942 compounds tested, 21 exhibited a substantial antiviral activity in Vero-81 cells. Among them, clofoctol, an antibacterial drug used for the treatment of bacterial respiratory tract infections, was further investigated due to its favorable safety profile and pharmacokinetic properties. Notably, the peak concentration of clofoctol that can be achieved in human lungs is more than 20 times higher than its IC 50 measured against SARS-CoV-2 in human pulmonary cells. This compound inhibits SARS-CoV-2 at a postentry step. Lastly, therapeutic treatment of human ACE2 receptor transgenic mice decreased viral load, reduced inflammatory gene expression and lowered pulmonary pathology. Altogether, these data strongly support clofoctol as a therapeutic candidate for the treatment of COVID-19 patients

Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma

International audienceCholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC. Here, we hypothesized that PBC might favor CCA immunosurveillance. In preclinical murine models of cholangitis challenged with syngeneic CCA, PBC (but not PSC) reduced the frequency of CCA development and delayed tumor growth kinetics. This PBC-related effect appeared specific to CCA as it was not observed against other cancers, including hepatocellular carcinoma. The protective effect of PBC was relying on type 1 and type 2 T cell responses and, to a lesser extent, on B cells. Single-cell TCR/RNA sequencing revealed the existence of TCR clonotypes shared between the liver and CCA tumor of a PBC host. Altogether, these results evidence a mechanistic overlapping between autoimmunity and cancer immunosurveillance in the biliary tract

Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal deathResearch in context

Summary: Background: We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline. Methods: We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. Findings: We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection. Interpretation: Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups. Funding: European Research Council (ERC) grant agreements No 810331, No 725149, No 804236, the European Union Horizon 2020 research and innovation program No 847941, the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche en Santé (ANRS) No ECTZ200878 Long Covid 2021 ANRS0167 SIGNAL, Agence Nationale de la recherche (ANR) grant agreements No ANR-19-CE16-0021-02, No ANR-11-LABEX-0009, No. ANR-10-LABEX-0046, No. ANR-16-IDEX-0004, Inserm Cross-Cutting Scientific Program HuDeCA, the CHU Lille Bonus H, the UK Medical Research Council (MRC) and National Institute of Health and care Research (NIHR)