NADPH oxidase activity is associated with cardiac osteopontin and pro-collagen type I expression in uremia.

International audienceCardiovascular disease is a frequent complication inducing mortality in chronic kidney disease (CKD) patients, which can be determined by both traditional risk factors and non-traditional risk factors such as malnutrition and oxidative stress. This study aimed to investigate the role of oxidative stress in uremia-induced cardiopathy in an experimental CKD model. CKD was induced in Sprague-Dawley rats by a 4-week diet supplemented in adenine, calcium and phosphorous and depleted in proteins. CKD was associated with a 3-fold increase in superoxide anion production from the NADPH oxidase in the left ventricle, but the maximal activity of mitochondrial respiratory chain complexes was not different. Although manganese mitochondrial SOD activity decreased, total SOD activity was not affected and catalase or GPx activities were increased, strengthening the major role of NADPH oxidase in superoxide anion output. Superoxide anion output was associated with enhanced expression of osteopontin (×7.7) and accumulation of pro-collagen type I (×3.7). To conclude, the increased activity of NADPH oxidase during CKD is associated with protein modifications which could activate a pathway leading to cardiac remodelling

”Dis, comment ça s'allume ?” Découverte de l'électricité à l'école primaire

Cet article présente une expérience pédagogique originale menée dans le cadre de l'année mondiale de la physique. Des étudiants de l'ENS de Cachan et de l'université Paris-Sud 11 Orsay ont fait découvrir les sciences physiques, et plus particulièrement l'électricité, à des élèves d'école primaire. Ce travail a été effectué à l'occasion du TER (travail d'étude et de recherche) de la première année du master IST (Information, Systèmes et Technologie), qui est en habilitation partagée entre l'université Paris-Sud 11 Orsay et l'ENS de Cachan. Au travers de cette communication, nous abordons dans un premier temps l'importance du travail préparatoire nécessaire à la réussite d'un tel projet ainsi que la démarche pédagogique adoptée par les étudiants. Ensuite, pour chaque séance détaillée dans l'article, nous en décrivons succinctement le déroulement afin de montrer les ajustements qui ont été nécessaires. Nous décrivons également la réaction des enfants et des étudiants. L'intérêt porté par les enfants montre qu une telle expérience aide à promouvoir la découverte des sciences dès l'école primaire et contribue à la formation des professeurs des écoles

" Dis, comment ça marche ? " Découverte des sciences à l'école primaire

Cet article présente un bilan des actions pédagogiques menées en école primaire suite à l'expérience proposée en 2005 dans le cadre de l'année mondiale de la physique [" Dis, comment ça s'allume ? " Découverte de l'électricité à l'école primaire, Stéphanie Cassan, Sylvie Galdin-Retailleau, Cécile Durieu, Cetsis 2005, Nancy.]. Depuis, des étudiants de l'ENS Cachan et de l'UFR des Sciences de l'université Paris-Sud 11 continuent à faire découvrir les sciences physiques à des élèves d'école primaire. Ce travail s'effectue dans le cadre de l'unité d'enseignement intitulée Travail d'Étude et de Recherche (TER) de la première année du master IST (Information, Systèmes et Technologie), qui est en habilitation partagée entre l'université Paris-Sud 11 et l'ENS Cachan. Dans cette communication, nous décrivons dans une première partie les interventions effectuées au cours de ces trois dernières années au sein de l'école du Centre d'Orsay. Ceci permet de montrer que de nombreux thèmes de la physique peuvent être traités, pourvu que les notions abordées soient bien préparées et que des expériences appropriées et réalisables par des enfants étayent les propos. Dans une seconde partie, nous faisons part de l'intervention menée cette année dans une école classée en zone d'éducation prioritaire (ZEP) ainsi que des interventions réalisées à partir de notre expérience par des collègues soit en école primaire, soit lors de la formation de professeurs des écoles

Functional evidence for an active role of B-type natriuretic peptide in cardiac remodelling and pro-arrhythmogenicity

International audienc

β-Adrenergic blockade combined with subcutaneous B-type natriuretic peptide: a promising approach to reduce ventricular arrhythmia in heart failure?

International audienc

Rapid Onset of Specific Diaphragm Weakness in a Healthy Murine Model of Ventilator-induced Diaphragmatic Dysfunction

International audienceBackground: Controlled mechanical ventilation is associated with ventilator-induced diaphragmatic dysfunction, which impedes weaning from mechanical ventilation. To design future clinical trials in humans, a better understanding of the molecular mechanisms using knockout models, which exist only in the mouse, is needed. The aims of this study were to ascertain the feasibility of developing a murine model of ventilator-induced diaphragmatic dysfunction and to determine whether atrophy, sarcolemmal injury, and the main proteolysis systems are activated under these conditions. Methods: Healthy adult male C57/BL6 mice were assigned to three groups: (1) mechanical ventilation with end-expiratory positive pressure of 2-4 cm H2O for 6 h (n = 6), (2) spontaneous breathing with continuous positive airway pressure of 2-4 cm H2O for 6 h (n = 6), and (3) controls with no specific intervention (n = 6). Airway pressure and hemodynamic parameters were monitored. Upon euthanasia, arterial blood gases and isometric contractile properties of the diaphragm and extensor digitorum longus were evaluated. Histology and immunoblotting for the main proteolysis pathways were performed. Results: Hemodynamic parameters and arterial blood gases were comparable between groups and within normal physiologic ranges. Diaphragmatic but not extensor digitorum longus force production declined in the mechanical ventilation group (maximal force decreased by approximately 40%) compared with the control and continuous positive airway pressure groups. No histologic difference was found between groups. In opposition with the calpains, caspase 3 was activated in the mechanical ventilation group. Conclusion: Controlled mechanical ventilation for 6 h in the mouse is associated with significant diaphragmatic but not limb muscle weakness without atrophy or sarcolemmal injury and activates proteolysis

Blue light promotes ascorbate synthesis by deactivating the PAS/LOV photoreceptor that inhibits GDP- l -galactose phosphorylase

Abstract Ascorbate (vitamin C) is an essential antioxidant in fresh fruits and vegetables. To gain insight into the regulation of ascorbate metabolism in plants, we studied mutant tomato plants (Solanum lycopersicum) that produce ascorbate-enriched fruits. The causal mutation, identified by a mapping-by-sequencing strategy, corresponded to a knock-out recessive mutation in a class of photoreceptor named PAS/LOV protein (PLP), which acts as a negative regulator of ascorbate biosynthesis. This trait was confirmed by CRISPR/Cas9 gene editing and further found in all plant organs, including fruit that accumulated 2 to 3 times more ascorbate than in the WT. The functional characterization revealed that PLP interacted with the 2 isoforms of GDP-l-galactose phosphorylase (GGP), known as the controlling step of the l-galactose pathway of ascorbate synthesis. The interaction with GGP occurred in the cytoplasm and the nucleus, but was abolished when PLP was truncated. These results were confirmed by a synthetic approach using an animal cell system, which additionally demonstrated that blue light modulated the PLP-GGP interaction. Assays performed in vitro with heterologously expressed GGP and PLP showed that PLP is a noncompetitive inhibitor of GGP that is inactivated after blue light exposure. This discovery provides a greater understanding of the light-dependent regulation of ascorbate metabolism in plants.Centre français de phénomique végétal

High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn’s Disease

International audienceBackground & AimsLittle is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn’s disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn’s perianal disease followed up in the Cancers Et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME) cohort.MethodsWe collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn’s disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex.ResultsAmong the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn’s lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn’s disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03).ConclusionsIn an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn’s disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer