Ezrin enhances line tension along transcellular tunnel edges via NMIIa driven actomyosin cable formation

Transendothelial cell macroaperture (TEM) tunnels control endothelium barrier function and are triggered by several toxins from pathogenic bacteria that provoke vascular leakage. Cellular dewetting theory predicted that a line tension of uncharacterized origin works at TEM boundaries to limit their widening. Here, by conducting high-resolution microscopy approaches we unveil the presence of an actomyosin cable encircling TEMs. We develop a theoretical cellular dewetting framework to interpret TEM physical parameters that are quantitatively determined by laser ablation experiments. This establishes the critical role of ezrin and non-muscle myosin II (NMII) in the progressive implementation of line tension. Mechanistically, fluorescence-recovery-after-photobleaching experiments point for the upstream role of ezrin in stabilizing actin filaments at the edges of TEMs, thereby favouring their crosslinking by NMIIa. Collectively, our findings ascribe to ezrin and NMIIa a critical function of enhancing line tension at the cell boundary surrounding the TEMs by promoting the formation of an actomyosin ring.Peer reviewe

Slc20a2, Encoding the Phosphate Transporter PiT2, Is an Important Genetic Determinant of Bone Quality and Strength.

Osteoporosis is characterized by low bone mineral density (BMD) and fragility fracture and affects over 200 million people worldwide. Bone quality describes the material properties that contribute to strength independently of BMD, and its quantitative analysis is a major priority in osteoporosis research. Tissue mineralization is a fundamental process requiring calcium and phosphate transporters. Here we identify impaired bone quality and strength in Slc20a2-/- mice lacking the phosphate transporter SLC20A2. Juveniles had abnormal endochondral and intramembranous ossification, decreased mineral accrual, and short stature. Adults exhibited only small reductions in bone mass and mineralization but a profound impairment of bone strength. Bone quality was severely impaired in Slc20a2-/- mice: yield load (-2.3 SD), maximum load (-1.7 SD), and stiffness (-2.7 SD) were all below values predicted from their bone mineral content as determined in a cohort of 320 wild-type controls. These studies identify Slc20a2 as a physiological regulator of tissue mineralization and highlight its critical role in the determination of bone quality and strength. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc

Abcès du foie en transplantation hépatique

L’abcès hépatique (AH) est une complication grave et peu décrite en transplantation hépatique (TH). Cette étude rétrospective monocentrique rassemble tous les cas d’AH survenus chez des patients avec TH (AH-TH) de 2009 à 2014. Chaque patient présentant un AH-TH a été comparé à 3 patients avec AH sans TH (AH-C). Quatorze AH-TH et 42 AH-C ont été analysés. Les caractéristiques cliniques et radiologiques étaient comparables entre les 2 groupes. Les AH-TH n’avaient pas d’hyperleucocytose au diagnostic (taux de leucocytes moyen = 9 G/L ; p=0,016). Les facteurs de risque d’AH retrouvés chez les AH-TH étaient la cholangite ischémique sur thrombose de l’artère hépatique (80% ; p0,05), la fistule biliaire (36% ; p=0,008), et la sténose de l’anastomose bilio-biliaire (29%, p>0,05). Les AH-C présentaient une néoplasie hépato-biliaire obstructive dans 40,5% des cas (p=0,005). Les données microbiologiques étaient comparables entre AH-TH et AH-C. Chez les AH-TH, les germes les plus représentés étaient les entérobactéries (64%) les entérocoques (29%), et les bactéries anaérobies (21%) ; 28% étaient documentés à des germes complexes : 1 AH à BGN non fermentant ERV et Candida, 1 AH à SARM, et 2 AH à BLSE. Les AH-TH étaient traités plus longuement par antibiotiques (9 semaines en moyenne ; p=0,02), mais les proportions d’AH-TH ayant eu un drainage de l’AH (79%), ou un drainage biliaire (74%), étaient comparables aux AH-C. Les AH-TH avaient deux fois plus souvent un traitement chirurgical associé (50%, p>0,05), et 36% étaient retransplantés. Les taux de mortalité (28%), et de récidive (57%) des AH-TH étaient similaires à ceux des AH-C

La gestion du parc de véhicules d'un répartiteur pharmaceutique

En tant que société de service, la CERP Rouen livre ses sociétaires trois fois par jour et cela six jours sur sept. Pour cela, elle possède une flotte de presque 600 véhicules. Dans un premier temps, cette étude montre comment est géré, au sein du groupe cette importante flotte. Après un certain nombre de constatations, nous décrirons les différentes offres de gestion de parcs qu'offre le marché. Puis, en fonction des besoins de l'entreprise, une solution, qui semble la mieux adaptée va être mise en test afin de déterminer les réels bénéfices d'un tel investissement.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Tiring job and work related injury road crashes in the GAZEL cohort.

International audienceThe objective was to describe at-work and commuting crashes occurring in a cohort of French employees and to investigate occupational risk factors. The subjects were employees of the French national electricity and gas companies, Electricit?e France and Gaz de France (EDF-GDF), who volunteered to join a research cohort (the GAZEL cohort which included 20,625 participants in 1989). Only crashes with injuries were considered. Crashes for the periods 1989-2001 were recorded together with the type of journey (commuting, work, private), the type of road-user, self-estimated responsibility, and injuries sustained by the subject. Annual incidences for gender/age groups and socio-occupational groups were computed for each of the two types of work related crashes. Occupational risk factor analyses were conducted using a Cox proportional hazards regression model with time-dependent covariates adjusting for the main confounders. A total of 146,285 person years at work were observed. Two indicators of self-reported work fatigue were associated with the occurrence of at-work crashes: "nervously tiring work" for males (RR=1.6, 95% CI [1.1; 2.3]), sustained standing for females (RR=3.0, 95% CI [1.0; 8.4]), adjusting for health status, location of residence, type of family, transport mode and mileage. As regards crashes while commuting, a self-reported uncomfortable position at work was a risk factor among women (RR=1.9, 95% CI [1.1; 3.3]). On the other hand, these occupational factors were not linked to road crashes in private trips. Work related road crashes seem then to be a matter for a specific prevention. Preventing employees from becoming exhausted should be considered as the first way to initiate such a prevention