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

Chikungunya virus-induced autophagy delays caspase-dependent cell death

Autophagy is an important survival pathway and can participate in the host response to infection. Studying Chikungunya virus (CHIKV), the causative agent of a major epidemic in India, Southeast Asia, and southern Europe, we reveal a novel mechanism by which autophagy limits cell death and mortality after infection. We use biochemical studies and single cell multispectral assays to demonstrate that direct infection triggers both apoptosis and autophagy. CHIKV-induced autophagy is mediated by the independent induction of endoplasmic reticulum and oxidative stress pathways. These cellular responses delay apoptotic cell death by inducing the IRE1α–XBP-1 pathway in conjunction with ROS-mediated mTOR inhibition. Silencing of autophagy genes resulted in enhanced intrinsic and extrinsic apoptosis, favoring viral propagation in cultured cells. Providing in vivo evidence for the relevance of our findings, Atg16L(HM) mice, which display reduced levels of autophagy, exhibited increased lethality and showed a higher sensitivity to CHIKV-induced apoptosis. Based on kinetic studies and the observation that features of apoptosis and autophagy were mutually exclusive, we conclude that autophagy inhibits caspase-dependent cell death but is ultimately overwhelmed by viral replication. Our study suggests that inducers of autophagy may limit the pathogenesis of acute Chikungunya disease

Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study

peer reviewedBackground: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI –∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8–27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI −0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17–0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33–2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16–0·47] and 0·21 [0·13–0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health—Programme Hospitalier de Recherche Clinique 2010

Fiction et réalités dans les lettres de rémission du duc de Lorraine au début du xviie siècle

« […] estans arrivez proche dud[ict] exposant, led[ict] Waultrin l’abordant de furie luy auroit dict en ses terme : Ha vérité Dieu, ton pistollet te seroit bon à cest heure ! Et de faict, s’estant mis en posture po[ur] le charger de sa hache […] led[ict] exposant se seroit aussy tost saisy dud[ict] pistollet sur lequel il estoit assis et en monstra le bout aud[ict] Gaultier, non à desseing de le charger, ains plustot pour luy donner terreur et le desmouvoir d’exécuter son audace et menace ; s..

Aerosol particles scavenging by a droplet: Microphysical modeling in the Greenfield gap

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Actes des 8èmes Journées Scientifiques du GDR 3544 Sciences du Bois: L'apport des Sciences du Bois à la société et au monde industriel

International audienceLe Groupement de Recherche en Sciences du bois (GDR3544 Sciences du Bois) a été créé en 2012 par le CNRS et renouvelé en 2016 pour 5 ans. La mission de ce groupement est : (1) de structurer la recherche sur le bois en France pour lui donner une visibilité nationale, (2) de contribuer au développement de la formation en sciences du bois et (3) de servir de relai aux réseaux internationaux de sciences du bois. Afin de répondre à ces objectifs, des journées scientifiques sont organisées ; elles doivent permettre de partager une culture commune, de promouvoir les travaux des laboratoires membres du GDR Bois, d’échanger sur des enjeux transversaux (relations internationales, formation, partage des ressources). Les trois journées sont ouvertes à tous les chercheurs intéressés par les sciences du bois, français comme étrangers, l'objectif étant d'accueillir un maximum de participants des laboratoires partenaires du GDR Bois et de favoriser la participation des jeunes chercheurs (doctorants ou post-doctorants). Dans l’esprit du GDR Bois, nous souhaitons que tous les chercheurs assistent à l’ensemble des journées annuelles car l’objectif n’est surtout pas de cloisonner les thématiques mais bien au contraire de développer une culture commune en espérant stimuler l’interdisciplinarité et les transferts de savoir-faire et d’outils entre thématiques. Les 7èmes journées annuelles du GDR Bois ont été organisées à Epinal, à l’Ecole Nationale des Technologies et Industries du Bois (ENSTIB) du 18 au 20 novembre 2019, avec le soutien du Laboratoire d’Etudes et de Recherche sur le Matériau Bois (LERMaB) auquel sont rattachés la plupart des personnels de recherche du site. Cette rencontre annuelle a rassemblé 172 membres provenant de 60 organismes. Elle a permis, au travers des exposés des conférenciers invités, d’évoquer les enjeux actuels de la filière forêt-bois autant que d’illustrer les diverses manières d’aborder l’étude du bois. Les participants ont pu échanger sur leurs travaux grâce aux présentations "flash" appuyées par des posters dont certains ont été primés par le biais d’un vote en ligne. Les actes de ces journées rassemblent les résumés des conférenciers invités (exposés) et ceux des contributions volontaires (posters). Cette année une session supplémentaire intitulée « participants distants » rassemble quelques contributions de participants étrangers n’ayant pu, au dernier moment, se rendre aux Journées du fait de la non-obtention d’un soutien espéré de l’AUF. Les actes sont diffusés sur la plateforme HAL, sous forme de collection « Sciences du bois » qui est destinée à diffuser les travaux des membres du GDR Bois. Des créneaux pour des réunions de groupes de travail (GT) ont été aménagés. Ces GT sont mis en place par les participants aux journées et certains, devenus récurrents, donnent lieu à des réunions thématiques en dehors de ces rencontres annuelles. Cette fois-ci, des ateliers de formation ont également été organisés en parallèle. Des visites d’entreprises ont aussi été proposées

Optimization of Acid Pretreatment in order to Increase the Phenolic Content of Picea abies Bark by Surface Response Methodology

International audienceThe purpose of this work was to determine the main factors influencing the phenolic content of bark during acid hydrolysis. The optimization of polysaccharides hydrolysis was done by response surface methodology. The hydrolysis was performed under atmospheric pressure in an aqueous solution of sulfuric acid. An experimental design was applied to analyze the effects of the reaction time (5 to 24 hours), acid concentration (3 to 20%), and solid/liquid ratio (1/10 to 1/5) on the weight loss, lignin content, holocellulose content, and sugar yield for the hydrolysis. The pretreated bark had a high lignin content of 60% resulting from hemicelluloses hydrolysis and phenolic compound condensation

Improving the scavenging kernel of aerosol particles by small water drops

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