Genetic consequences of climate change for northern plants

Climate change will lead to loss of range for many species, and thus to loss of genetic diversity crucial for their long-term persistence. We analysed range-wide genetic diversity (amplified fragment length polymorphisms) in 9581 samples from 1200 populations of 27 northern plant species, to assess genetic consequences of range reduction and potential association with species traits. We used species distribution modelling (SDM, eight techniques, two global circulation models and two emission scenarios) to predict loss of range and genetic diversity by 2080. Loss of genetic diversity varied considerably among species, and this variation could be explained by dispersal adaptation (up to 57%) and by genetic differentiation among populations (FST; up to 61%). Herbs lacking adaptations for long-distance dispersal were estimated to lose genetic diversity at higher rate than dwarf shrubs adapted to long-distance dispersal. The expected range reduction in these 27 northern species was larger than reported for temperate plants, and all were predicted to lose genetic diversity according to at least one scenario. SDM combined with FST estimates and/or with species trait information thus allows the prediction of species' vulnerability to climate change, aiding rational prioritization of conservation efforts

Up-regulation of the ATP-binding cassette transporter A1 inhibits hepatitis C virus infection.

International audienceHepatitis C virus (HCV) establishes infection using host lipid metabolism pathways that are thus considered potential targets for indirect anti-HCV strategies. HCV enters the cell via clathrin-dependent endocytosis, interacting with several receptors, and virus-cell fusion, which depends on acidic pH and the integrity of cholesterol-rich domains of the hepatocyte membrane. The ATP-binding Cassette Transporter A1 (ABCA1) mediates cholesterol efflux from hepatocytes to extracellular Apolipoprotein A1 and moves cholesterol within cell membranes. Furthermore, it generates high-density lipoprotein (HDL) particles. HDL protects against arteriosclerosis and cardiovascular disease. We show that the up-regulation of ABCA1 gene expression and its cholesterol efflux function in Huh7.5 hepatoma cells, using the liver X receptor (LXR) agonist GW3965, impairs HCV infection and decreases levels of virus produced. ABCA1-stimulation inhibited HCV cell entry, acting on virus-host cell fusion, but had no impact on virus attachment, replication, or assembly/secretion. It did not affect infectivity or properties of virus particles produced. Silencing of the ABCA1 gene and reduction of the specific cholesterol efflux function counteracted the inhibitory effect of the GW3965 on HCV infection, providing evidence for a key role of ABCA1 in this process. Impaired virus-cell entry correlated with the reorganisation of cholesterol-rich membrane microdomains (lipid rafts). The inhibitory effect could be reversed by an exogenous cholesterol supply, indicating that restriction of HCV infection was induced by changes of cholesterol content/distribution in membrane regions essential for virus-cell fusion. Stimulation of ABCA1 expression by GW3965 inhibited HCV infection of both human primary hepatocytes and isolated human liver slices. This study reveals that pharmacological stimulation of the ABCA1-dependent cholesterol efflux pathway disrupts membrane cholesterol homeostasis, leading to the inhibition of virus-cell fusion and thus HCV cell entry. Therefore besides other beneficial roles, ABCA1 might represent a potential target for HCV therapy

HIV-1 Efficient Entry in Inner Foreskin Is Mediated by Elevated CCL5/RANTES that Recruits T Cells and Fuels Conjugate Formation with Langerhans Cells

Male circumcision reduces acquisition of HIV-1 by 60%. Hence, the foreskin is an HIV-1 entry portal during sexual transmission. We recently reported that efficient HIV-1 transmission occurs following 1 h of polarized exposure of the inner, but not outer, foreskin to HIV-1-infected cells, but not to cell-free virus. At this early time point, Langerhans cells (LCs) and T-cells within the inner foreskin epidermis are the first cells targeted by the virus. To gain in-depth insight into the molecular mechanisms governing inner foreskin HIV-1 entry, foreskin explants were inoculated with HIV-1-infeceted cells for 4 h. The chemokine/cytokine milieu secreted by the foreskin tissue, and resulting modifications in density and spatial distribution of T-cells and LCs, were then investigated. Our studies show that in the inner foreskin, inoculation with HIV-1-infected cells induces increased CCL5/RANTES (1.63-fold) and decreased CCL20/MIP-3-alpha (0.62-fold) secretion. Elevated CCL5/RANTES mediates recruitment of T-cells from the dermis into the epidermis, which is blocked by a neutralizing CCL5/RANTES Ab. In parallel, HIV-1-infected cells mediate a bi-phasic modification in the spatial distribution of epidermal LCs: attraction to the apical surface at 1 h, followed by migration back towards the basement membrane later on at 4 h, in correlation with reduced CCL20/MIP-3-alpha at this time point. T-cell recruitment fuels the continuous formation of LC-T-cell conjugates, permitting the transfer of HIV-1 captured by LCs. Together, these results reveal that HIV-1 induces a dynamic process of immune cells relocation in the inner foreskin that is associated with specific chemokines secretion, which favors efficient HIV-1 entry at this site

HIV-1 co-receptor usage:influence on mother-to-child transmission and pediatric infection

Viral CCR5 usage is not a predictive marker of mother to child transmission (MTCT) of HIV-1. CXCR4-using viral variants are little represented in pregnant women, have an increased although not significant risk of transmission and can be eventually also detected in the neonates. Genetic polymorphisms are more frequently of relevance in the child than in the mother. However, specific tissues as the placenta or the intestine, which are involved in the prevalent routes of infection in MTCT, may play an important role of selective barriers

Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model.

International audienc

Hepatitis C virus: Morphogenesis, infection and therapy

Hepatitis C virus (HCV) is a major cause of liver diseases including liver cirrhosis and hepatocellular carcinoma. Approximately 3% of the world population is infected with HCV. Thus, HCV infection is considered a public healthy challenge. It is worth mentioning, that the HCV prevalence is dependent on the countries with infection rates around 20% in high endemic countries. The review summarizes recent data on HCV molecular biology, the physiopathology of infection (immune-mediated liver damage, liver fibrosis and lipid metabolism), virus diagnostic and treatment. In addition, currently available in vitro, ex vivo and animal models to study the virus life cycle, virus pathogenesis and therapy are described. Understanding of both host and viral factors may in the future lead to creation of new approaches in generation of an efficient therapeutic vaccine

Caracterisation a l'aide d'anticorps humains autoimmuns de deux antigenes apparentes au facteur TFIIIA et d'un antigene nucleaire lie au cycle cellulaire

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model.

International audienc

The remarkable history of the hepatitis C virus

International audienc

Rôle de l'omnipraticien dans la prévention et la prise en charge des dysfonctions oro-faciales chez le jeune enfant

La dysfonction consiste en l exercice incorrect d une ou plusieurs fonctions naturelles. Ventilation, déglutition, succion, mastication et phonation sont les principales fonctions oro-faciales de l Homme. Ces fonctions sont pour certaines anciennes à l échelle de l évolution, d autres très récentes. Elles apparaissent précocement, au cours de la vie intra-utérine et dans les premières années de l enfant, et évoluent en interactions avec les structures anatomiques en cours de développement. Leur maturation est également influencée par le développement psychologique et émotionnel de l individu. Prévenir l apparition d une dysfonction, c est d abord connaître les facteurs qui l influencent, éviter les habitudes et les attitudes néfastes, et donner à l enfant toutes les chances de jouir d une croissance harmonieuse en adoptant des conduites favorisant l exercice fonctionnel et sa maturation. L omnipraticien va endosser dans ce but un rôle d interlocuteur et de conseiller. Il est également l acteur de santé privilégié qui est à même de dépister précocement un verrou fonctionnel, et d adopter, personnellement, ou en adressant le jeune patient à ses confrères, la stratégie thérapeutique adéquate.Malfunction consist in a incorrect exercise of natual fonction. The humain main oro-facial functions are ventilation, deglutition, suction, mastication and phonation. Some of these functions appeared early in the human evolution process, others more recently. All of them appear in the early stage of the in-utero development and during the forst years of a child s life, all the while evolving and interacting with anatomical structures. Their maturation is equally influenced by the psychologic and emotional individual development. Preventing malfunction appearance begins with understanding factors that might influence it, avoiding bad habits and harmful postures, and giving the child the opportunity to develop gracefully by encouraging behaviors favoring the function exercice and its proper maturation. The practitioner will endorse a conselor and interlocutor role in this endeavour. As a main healthcare professional, he is able to detect functional deadlocks at an early stage and to put into practice, either personally, or by referinf the young patient to a colleague, the appropriate therapeutic strategy.BORDEAUX2-BU Sci.Homme/Odontol. (330632102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF