MouR controls the expression of the Listeria monocytogenes Agr system and mediates virulence

The foodborne pathogen Listeria monocytogenes (Lm) causes invasive infection in susceptible ani- mals and humans. To survive and proliferate within hosts, this facultative intracellular pathogen tightly coordinates the expression of a complex regulatory network that controls the expression of virulence fac- tors. Here, we identified and characterized MouR, a novel virulence regulator of Lm. Through RNA-seq transcriptomic analysis, we determined the MouR regulon and demonstrated how MouR positively con- trols the expression of the Agr quorum sensing sys- tem (agrBDCA) of Lm. The MouR three-dimensional structure revealed a dimeric DNA-binding transcrip- tion factor belonging to the VanR class of the GntR superfamily of regulatory proteins. We also showed that by directly binding to the agr promoter region, MouR ultimately modulates chitinase activity and biofilm formation. Importantly, we demonstrated by in vitro cell invasion assays and in vivo mice infec- tions the role of MouR in Lm virulence.Peer reviewe

Ovarian thrombosis and uterine synechiae after arterial embolization for a late postpartum haemorrhage

International audienc

Supplémenter le repas en leucine permet de corriger le défaut d'anabolisme protéique musculaire postprandial du rat âgé

National audienc

EPURE Transplant (Eplerenone in Patients Undergoing Renal Transplant) study: study protocol for a randomized controlled trial

Abstract Background Despite advances in immunosuppressive therapy, kidney graft survival has failed to improve during the last decades. Ischemia/reperfusion injury (IRI) is one of the main pathophysiological mechanisms underlying delayed graft function, which is associated with poor long-term graft survival. Due to organ shortage, the proportion of grafts from expanded criteria donors (ECDs) is ever growing. These grafts may particularly benefit from IRI prevention. In preclinical models, mineralocorticoid receptor antagonists (MRAs) have been shown to efficiently prevent IRI. This study aims to assess the effect of MRA administration in the early phase of kidney transplantation (KT) among recipients of ECD grafts on mid-term graft function. Methods/design This is a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients on hemodialysis and undergoing a single or a dual KT from an ECD will be eligible for inclusion. We plan to randomize 132 patients. Included patients will be randomized (1:1) to receive either eplerenone 25 mg every 12 h during 4 days (the first dose being administered just prior to KT) or placebo. The primary outcome is graft function at 3 months, assessed by glomerular filtration rate (GFR, in mL/min/1.73m2) measured using iohexol clearance. Secondary outcomes include (1) proportion of patients with either dialysis dependency or a GFR < 30 mL/min/1.73m2 at 3 months, (2) proportion of patients with immediate, slow, or delayed graft function, (3) proteinuria at 3 months, (4) occurrence of hyperkalemia during the first week following KT, (5) length of hospital stay for the KT, and (6) occurrence of biopsy-proven acute rejection in the first 3 months following KT. Estimated GFR, graft, and patient survival will also be collected at 1, 3, and 10 years via the national database of organ recipients. Discussion Improvement of ECD grafts is a public health priority, since better ECD outcomes could eventually limit organ shortage. MRA administration in the early phase of KT may prevent IRI and subsequently improve mid-term graft function. The trial will also assess the safety of MRA administration in this population, primarily the absence of threatening hyperkalemia. Trial registration ClinicalTrials.gov, NCT02490904. Registered on 1 July 2015

Enseignement Scientifique 1re Manuel élève 2019

National audienceUn ou plusieurs des objectifs généraux du programme abordés dans chaque chapitre : la compréhension du mode de fonctionnement de la science, les interactions science-société, l'histoire des idées en sciences. Les enjeux et débats associés à chaque thème systématiquement traités dans les chapitres du thème. De nombreux outils proposés pour le projet expérimental et numérique. De nombreuses propositions d'activités pratiques... très faciles à mettre en uvre : expérimentations, modélisations, utilisations de systèmes d'information géopgraphique (SIG). Des doubles pages de documents avec des activités de type varié : tâches complexes, projets, questionnement guidés. Des développements mathématiques soigneusement présentés et expliqués Une dizaine d'exercices par chapitre pour s'entraîner pour le bac sur les trois types de savoir-faire : calcul, synthèse et description écrite, analyse documentaire

Azacitidine for patients with Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome (VEXAS) and myelodysplastic syndrome: data from the French VEXAS registry

International audienceAzacitidine can be effective in myelodysplastic syndromes (MDS) associated with inflammatory/autoimmune diseases. Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome (VEXAS) is a new monogenic autoinflammatory syndrome caused by somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutation, often associated with MDS, whose treatment is difficult and not yet codified. Based on a French nationwide registry of 116 patients with VEXAS, we report the efficacy and safety of azacitidine treatment in 11 patients with VEXAS with MDS. Clinical response of VEXAS to azacitidine was achieved in five patients (46%), during 6, 8+, 12, 21, 27+ months respectively, suggesting that azacitidine can be effective in selected patients with VEXAS and associated MDS