A selective PIKfyve inhibitor blocks PtdIns(3,5)P2 production and disrupts endomembrane transport and retroviral budding

Phosphoinositides have crucial roles in cellular controls, many of which have been established through the use of small-molecule inhibitors. Here, we describe YM201636, a potent inhibitor of the mammalian class III phosphatidylinositol phosphate kinase PIKfyve, which synthesizes phosphatidylinositol 3,5-bisphosphate. Acute treatment of cells with YM201636 shows that the PIKfyve pathway is involved in the sorting of endosomal transport, with inhibition leading to the accumulation of a late endosomal compartment and blockade of retroviral exit. Inhibitor specificity is shown by the use of short interfering RNA against the target, as well as by rescue with the drug-resistant yeast orthologue Fab1. We concluded that the phosphatidylinositol 3,5-bisphosphate pathway is integral to endosome formation, determining morphology and cargo flux

Les enfants comprennent-ils des phrases décrivant les événements inconnus ?

Bramaud du Boucheron Geneviève, Perez Christine. Les enfants comprennent-ils des phrases décrivant les événements inconnus ?. In: Bulletin de psychologie, tome 32 n°341, 1979. Compréhension du langage. pp. 757-761

Dexamethasone Causes Sustained Expression of Mitogen-Activated Protein Kinase (MAPK) Phosphatase 1 and Phosphatase-Mediated Inhibition of MAPK p38

The stress-activated protein kinase p38 stabilizes a number of mRNAs encoding inflammatory mediators, such as cyclooxygenase 2 (Cox-2). In HeLa cells the anti-inflammatory glucocorticoid dexamethasone destabilizes Cox-2 mRNA by inhibiting p38 function. Here we demonstrate that this effect is phosphatase dependent. Furthermore, in HeLa cells dexamethasone induced the sustained expression of mitogen-activated protein kinase phosphatase 1 (MKP-1), a potent inhibitor of p38 function. The inhibition of p38 and the induction of MKP-1 by dexamethasone occurred with similar dose dependence and kinetics. No other known p38 phosphatases were induced by dexamethasone, and other cell types which failed to express MKP-1 also failed to inhibit p38 in response to dexamethasone. The proinflammatory cytokine interleukin 1 (IL-1) induced MKP-1 expression in a p38-dependent manner and acted synergistically with dexamethasone to induce MKP-1 expression. In HeLa cells treated with IL-1 or IL-1 and dexamethasone, the dynamics of p38 activation mirrored the expression of MKP-1. These observations suggest that MKP-1 participates in a negative-feedback loop which regulates p38 function and that dexamethasone may inhibit proinflammatory gene expression in part by inducing MKP-1 expression

A Single Amino Acid in the DNA Binding Regions of STAT5A and STAT5B Confers Distinct DNA Binding Specificities

International audienceSTAT5A and STAT5B are two highly related transcription factors encoded by two distinct genes. STAT5A and STAT5B are activated by a broad range of cytokines and growth factors. Although they can be differentially activated, the functional difference between these two molecules relative to their structure is not known. Here we demonstrated that STAT5A and STAT5B homodimers have distinct DNA binding preferences. Chimeric STAT5 molecules allowed us to identify a region between amino acid 420 and 545 responsible for the DNA binding specificity. This region is located in the previously characterized DNA binding region of STAT proteins. Sequence comparison between STAT5A and STAT5B from different species showed a difference of 5 amino acids in the region 420-545 between STAT5A and STAT5B. Substitution of these amino acids demonstrated that a glycine residue at position 433 in STAT5B and a glutamic residue at a similar position in STAT5A determined the DNA binding specificity. These data indicate that STAT5A and STAT5B homodimers may have distinct function and probably regulate the expression of common as well as distinct genes

Nathan Wachtel. Histoire et anthropologie

De La Vision des vaincus (1971) aux Mémoires marranes (2011) en passant par Le Retour des ancêtres (1990), l’oeuvre de Nathan Wachtel chemine, un demi-siècle durant, sur les lignes de crête du dialogue – productif souvent, critique parfois – entre l’anthropologie et l’histoire. Du compagnonnage avec l’« anthropologie historique » des Annales à la pratique d’une « histoire régressive » qui se pose en remède aux ethnohistoires les moins réflexives, ce parcours de recherche exemplaire a nourri quantité de débats et de travaux. Surtout, ses modes d’enquête et ses objets de prédilection gardent une stupéfiante actualité. Qu’il s’agisse de marier le compte-rendu ethnographique et les matériaux d’archive sans faire injure à leurs silences respectifs, de scruter le revers « indigène » de la Conquête et de ses mises en récit, d’analyser la fluidité des appartenances confessionnelles aux marches d’un ordre impérial toujours vacillant, ou encore de décrire les fabriques locales de l’histoire et du territoire, les ouvrages de Nathan Wachtel restent tout à la fois des jalons et des sources d’inspiration. Il s’agit ainsi, à l’occasion d’une série de tables-rondes consacrées aux différents aspects de l’œuvre de Nathan Wachtel, non seulement de rendre compte de l’évolution des rapports entre histoire et anthropologie dans le champ académique français depuis les années 1970, mais aussi de voir quel parti les chercheurs d’aujourd’hui tirent de la relecture de ses travaux

Art et pouvoir

« Des images de l’histoire de l’art à celles des médias visuels de masse, des arts visuels à la culture visuelle, l’image poursuit sa marche triomphale. » – Peter Weibel Alliances, résistances, compromissions, les rapports entre l’art et le pouvoir s’imposent dans le monde visuel, du portrait au muralisme, de l’empire au musée, de la propagande à l’iconoclasme. Investissant des objets, des méthodes, des géographies et des temps multiples, l’histoire de l’art réinterroge les pouvoirs de l’image

Unravelling the determinants of human health in French Polynesia: the MATAEA project

BackgroundFrench Polynesia is a French overseas collectivity in the Southeast Pacific, comprising 75 inhabited islands across five archipelagoes. The human settlement of the region corresponds to the last massive migration of humans to empty territories, but its timeline is still debated. Despite their recent population history and geographical isolation, inhabitants of French Polynesia experience health issues similar to those of continental countries. Modern lifestyles and increased longevity have led to a rise in non-communicable diseases (NCDs) such as obesity, diabetes, hypertension, and cardiovascular diseases. Likewise, international trade and people mobility have caused the emergence of communicable diseases (CDs) including mosquito-borne and respiratory diseases. Additionally, chronic pathologies including acute rheumatic fever, liver diseases, and ciguatera, are highly prevalent in French Polynesia. However, data on such diseases are scarce and not representative of the geographic fragmentation of the population. ObjectivesThe MATAEA project aims to estimate the prevalence of several NCDs and CDs in the population of the five archipelagoes, and identify associated risk factors. Moreover, genetic analyses will contribute to determinate the sequence and timings of the peopling history of French Polynesia, and identify causal links between past genetic adaptation to island environments, and present-day susceptibility to certain diseases. MethodsThis cross-sectional survey is based on the random selection of 2,100 adults aged 18-69 years and residing on 18 islands from the five archipelagoes. Each participant answered a questionnaire on a wide range of topics (including demographic characteristics, lifestyle habits and medical history), underwent physical measurements (height, weight, waist circumference, arterial pressure, and skin pigmentation), and provided biological samples (blood, saliva, and stool) for biological, genetic and microbiological analyses. ConclusionFor the first time in French Polynesia, the MATAEA project allows to collect a wide range of data to explore the existence of indicators and/or risk factors for multiple pathologies of public health concern. The results will help health authorities to adapt actions and preventive measures aimed at reducing the incidence of NCDs and CDs. Moreover, the new genomic data generated in this study, combined with anthropological data, will increase our understanding of the peopling history of French Polynesia

Predictive usefulness of RT-PCR testing in different patterns of Covid-19 symptomatology: analysis of a French cohort of 12,810 outpatients

International audienceReverse transcriptase polymerase chain reaction (RT-PCR) is a key tool to diagnose Covid-19. Yet it may not be the most efficient test in all patients. In this paper, we develop a clinical strategy for prescribing RT-PCR to patients based on data from COVIDOM, a French cohort of 54,000 patients with clinically suspected Covid-19, including 12,810 patients tested by RT-PCR. We use a machine-learning algorithm (decision tree) in order to predict RT-PCR results based on the clinical presentation. We show that symptoms alone are sufficient to predict RT-PCR outcome with a mean average precision of 86%. We identify combinations of symptoms that are predictive of RT-PCR positivity (90% for anosmia/ageusia) or negativity (only 30% of RT-PCR+\,for a subgroup with cardiopulmonary symptoms): in both cases, RT-PCR provides little added diagnostic value. We propose a prescribing strategy based on clinical presentation that can improve the global efficiency of RT-PCR testing