Large-scale identification of human genes implicated in epidermal barrier function

Identification of genes expressed in epidermal granular keratinocytes by ORESTES, including a number that are highly specific for these cells

A new classification of HLA-DRB1 alleles differentiates predisposing and protective alleles for autoantibody production in rheumatoid arthritis

The HLA-DRB1 gene was reported to be associated with anticitrullinated protein/peptide autoantibody (ACPA) production in rheumatoid arthritis (RA) patients. A new classification of HLA-DRB1 alleles, reshaping the shared epitope (SE) hypothesis, was recently found relevant in terms of RA susceptibility and structural severity

Un cadre interprétatif pour enrichir la réflexivité : le cas d’une formation à la médiation civile et commerciale

L’interrogation des pratiques professionnelles par les professionnels eux-mêmes en discussion collective leur permet d’améliorer leur compréhension des activités de travail et de développer des compétences à la réflexivité. Dans le champ de l’éducation, un enjeu est de proposer de nouveaux cadres interprétatifs afin que les professionnels perçoivent leur activité sous de nouveaux angles et que les échanges sur les pratiques soient enrichis. Le but de cet article est de proposer un nouveau cadre interprétatif mobilisable pour l’étude des activités professionnelles qui se matérialisent à travers des interactions langagières. Le cadre exploite des modèles, théories, notions, méthodologies issues des sciences du langage et de la psychologie de la communication. L’enjeu de l’article est d’étudier l’apport de ce cadre dans un processus de formation à la médiation civile et commerciale destinée à des avocats et des notaires. Le dispositif de formation exploite la technique du jeu de rôle, les résultats d’analyse des productions émises en jeu de rôle–analyse basée sur le cadre –, une discussion collective consécutive au jeu de rôle et une discussion en allo-confrontation au cours de laquelle les résultats d’analyse mobilisant le cadre sont présentés. De cette étude, il ressort que la restitution des résultats d’analyse du jeu de rôle basée sur ce cadre permet d’éclairer l’activité communicationnelle sous des angles auxquels les formés n’ont pas accès d’emblée, de mettre au jour des dysfonctionnements/phénomènes restés jusque-là inaperçus. Surtout, cette restitution fournit les outils conceptuels à une réflexivité utile, le cas échéant, à l’optimisation des pratiques professionnelles.Reflection on professional practices by professionals themselves in collective discussions allows them to improve their understanding of work activities, and to develop reflexivity skills. In the educational field, one challenge is to offer new interpretive frameworks allowing professionals to perceive their activity in a new light and enhance reflection on practices in collective discussion. The goal of this paper is to present a new interpretive framework that can be used to study professional practices that take place through linguistic interactions. This framework includes models, theories, concepts and methodologies taken from language sciences and the psychology of communication. The issue in this paper is to study how this framework contributes to the process of training lawyers and notaries in civil and commercial mediation. The training system uses: (i) the role-play technique, (ii) the results of the analysis of verbal productions voiced during role-play (analysis based on the framework), (iii) a collective discussion consecutive to the role-play and (iv) a discussion in allo-confrontation, during which the results of the analysis are presented. From this study, we can see that the restitution of the results of the role play analysis based on the framework clarifies the communicational activity from viewpoints that are not immediately accessible to the trainees. It also makes it possible to revise dysfunctions/phenomena that have so far gone unnoticed. Above all, it provides conceptual tools for a reflexivity that might be useful in the optimization of professional practice

Diagnostic value of anti-human citrullinated fibrinogen ELISA and comparison with four other anti-citrullinated protein assays

We studied the diagnostic performance of the anti-human citrullinated fibrinogen antibody (AhFibA) ELISA for rheumatoid arthritis (RA) in a consecutive cohort (population 1) and evaluated the agreement between the AhFibA ELISA and four other assays for anti-citrullinated protein/peptide antibodies (ACPAs) as well as rheumatoid factor in patients with longstanding RA (population 2). Population 1 consisted of 1024 patients with rheumatic symptoms; serum samples from these patients were sent to our laboratory for ACPA testing within the context of a diagnostic investigation for RA. Ninety-two of these patients were classified as having RA according to the American College of Rheumatology criteria and 463 were classified as non-RA patients. Population 2 consisted of 180 patients with longstanding RA and was used to assess agreement and correlations between five ACPA assays: anti-cyclic citrullinated peptide (CCP)1 and anti-CCP2 antibodies were detected using a commercially available ELISA, AhFibA using ELISA, and anti-PepA and anti-PepB antibodies using line immunoassay. Applying previously proposed cut-offs for AhFibA, we obtained a sensitivity of 60.9% and a specificity of 98.7% in population 1. Receiver operating characteristic curve analysis could not detect a significant difference in diagnostic performance between the AhFibA ELISA and anti-CCP2 assay. Performing a hierarchical nearest neighborhood cluster analysis of the five different ACPA assays in population 2, we identified two clusters: a cluster of anti-pepA, anti-pepB and anti-CCP1, and a cluster of AhFibA and anti-CCP2. In conclusion, we found that AhFibA and anti-CCP2 antibodies had similar diagnostic performance. However, disagreement between ACPA tests may occur

Sphingosine Kinase-1 Is Central to Androgen-Regulated Prostate Cancer Growth and Survival

BACKGROUND: Sphingosine kinase-1 (SphK1) is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival. METHODOLOGY/PRINCIPAL FINDINGS: Short-term androgen removal induced a rapid and transient SphK1 inhibition associated with a reduced cell growth in vitro and in vivo, an event that was not observed in the hormono-insensitive PC-3 cells. Supporting the critical role of SphK1 inhibition in the rapid effect of androgen depletion, its overexpression could impair the cell growth decrease. Similarly, the addition of dihydrotestosterone (DHT) to androgen-deprived LNCaP cells re-established cell proliferation, through an androgen receptor/PI3K/Akt dependent stimulation of SphK1, and inhibition of SphK1 could markedly impede the effects of DHT. Conversely, long-term removal of androgen support in LNCaP and C4-2B cells resulted in a progressive increase in SphK1 expression and activity throughout the progression to androgen-independence state, which was characterized by the acquisition of a neuroendocrine (NE)-like cell phenotype. Importantly, inhibition of the PI3K/Akt pathway--by negatively impacting SphK1 activity--could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors. Fascinatingly, the reversability of the NE phenotype by exposure to normal medium was linked with a pronounced inhibition of SphK1 activity. CONCLUSIONS/SIGNIFICANCE: We report the first evidence that androgen deprivation induces a differential effect on SphK1 activity in hormone-sensitive prostate cancer cell models. These results also suggest that SphK1 activation upon chronic androgen deprivation may serve as a compensatory mechanism allowing prostate cancer cells to survive in androgen-depleted environment, giving support to its inhibition as a potential therapeutic strategy to delay/prevent the transition to androgen-independent prostate cancer

MIL-91(Ti), a small pore metal-organic framework which fulfils several criteria : an upscaled green synthesis, excellent water stability, high CO2 selectivity and fast CO2 transport

The research leading to these results has received funding from the European Community Seventh Framework Program (FP7/2007-2013) [grant agreement number 608490] (project M4CO2) and from the ANR ‘CHESDENS’ (ANR-13-SEED-0001-01).A multidisciplinary approach combining advanced experimental and modelling tools was undertaken to characterize the promises of a small-pore type Ti-based metal-organic framework, MIL-91(Ti) for CO2 capture. This material was prepared using two synthesis strategies, i.e. under hydrothermal conditions and under reflux, and its single component adsorption behaviour with respect to CO2, CH4 and N2 was first revealed by gravimetry measurements. This hydrophilic and highly water stable MOF is characterized by a relatively high CO2 adsorption enthalpy. Molecular simulations combined with in situ powder X-ray diffraction evidenced that this is due to the combined interaction of this probe with N-H and P-O groups in the phosphonate linker. High CO2 selectivities in the presence of either N2 or CH4 were also predicted and confirmed by co-adsorption measurements. The possibility to prepare this sample under reflux represents an environmentally friendly route which can easily be upscaled. This green synthesis route, excellent water stability, high selectivities and relatively fast transport kinetics of CO2 are significant points rendering this sample of utmost interest for CO2 capture.PostprintPostprintPeer reviewe

Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis

Antibodies to citrulline-modifi ed proteins have a high diagnostic value in rheumatoid arthritis (RA). However, their biological role in disease development is still unclear. To obtain insight into this question, a panel of mouse monoclonal antibodies was generated against a major triple helical collagen type II (CII) epitope (position 359 – 369; ARGLTGRPGDA) with or without arginines modifi ed by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients ’ synovial fl uid demonstrates that cartilage-derived CII is indeed citrullinated in vivo. The structure determination of a Fab fragment of one of these antibodies in complex with a citrullinated peptide showed a surprising beta -turn conformation of the peptide and provided information on citrulline recognition. Based on these findings, we propose that autoimmunity to CII, leading to the production of antibodies specific for both native and citrullinated CII, is an important pathogenic factor in the development of RA