Enjeux, difficultés et modalités de l’expression sur le travail : point de vue de la clinique médicale du travail de Philippe Davezies« Les dilemmes d’un débat centré sur l’activité »

Introduction à la discussion À partir de sa démarche de médecin du travail, d’ergonome et d’universitaire enclin à ouvrir son savoir au milieu syndical, Philippe Davezies nous amène à renouveler notre prise en charge des questions de conditions de travail. Avec d’autres chercheurs, il nous conduit à envisager qu’au-delà des « conditions de travail », ce sont les « conditions d’accomplissement de soi dans le travail » qu’il importe désormais de saisir si l’on veut contrer Le nouvel esprit du c..

Enjeux, difficultés et modalités de l’expression sur le travail : point de vue de la clinique médicale du travail de Philippe Davezies« Les dilemmes d’un débat centré sur l’activité »

Introduction à la discussion À partir de sa démarche de médecin du travail, d’ergonome et d’universitaire enclin à ouvrir son savoir au milieu syndical, Philippe Davezies nous amène à renouveler notre prise en charge des questions de conditions de travail. Avec d’autres chercheurs, il nous conduit à envisager qu’au-delà des « conditions de travail », ce sont les « conditions d’accomplissement de soi dans le travail » qu’il importe désormais de saisir si l’on veut contrer Le nouvel esprit du c..

When voluntary paracetamol overdose requires a drug challenge

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When voluntary paracetamol overdose requires a drug challenge

International audienceno abstrac

Inhibition of HIV-1 replication by cell-penetrating peptides binding rev

International audienceNew therapeutic agents able to block HIV-1 replication are eagerly sought after to increase the possibilities of treatment of resistant viral strains. In this report, we describe a rational strategy to identify small peptide sequences owning the dual property of penetrating within lymphocytes and of binding to a protein target. Such sequences were identified for two important HIV-1 regulatory proteins, Tat and Rev. Their association to a stabilizing domain consisting of human small ubiquitin-related modifier-1 (SUMO-1) allowed the generation of small proteins named SUMO-1 heptapeptide protein transduction domain for binding Tat (SHPT) and SUMO-1 heptapeptide protein transduction domain for binding Rev (SHPR), which are stable and efficiently penetrate within primary lymphocytes. Analysis of the antiviral activity of these proteins showed that one SHPR is active in both primary lymphocytes and macrophages, whereas one SHPT is active only in the latter cells. These proteins may represent prototypes of new therapeutic agents targeting the crucial functions exerted by both viral regulatory factors

Human bronchial epithelium orchestrates dendritic cell activation in severe asthma

International audienceThe innate immune response is impaired in asthma, with increased epithelial release of C-X-C motif chemokine ligand (CXCL) 8, interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP). We hypothesised that dendritic cells might modulate the hyperresponsive epithelium in severe asthma. For this purpose, we investigated epithelial-dendritic crosstalk in normal and diseased conditions, and because ultrafine particulate matter may affect asthmatic airways, we investigated its impact on this crosstalk. Air-liquid interface cultures of human bronchial epithelial cells (HBEC) of control subjects (cHBEC) or severe asthma patients (saHBEC) were co-cultured with monocyte-derived dendritic cells (moDC). Increased release of CXCL8, TSLP and IL-33 from saHBEC contrasted with cHBEC producing CXCL10 and CCL2. Regarding moDC activation, saHBEC co-cultures induced only upregulation of CD86 expression, while cHBEC yielded full moDC maturation with HLA-DR, CD80, CD86 and CD40 upregulation. Particulate matter stimulation of HBEC had no effect on cHBEC but stimulated CXCL8 and IL-33 release in saHBEC. Particulate matter impaired epithelium signalling (TSLP, IL-33 and CXCL8) in saHBEC co-cultures despite C-C chemokine ligand 2 induction. Crosstalk between HBEC and moDC can be established in vitro, driving a T1-type response with cHBEC and a T2-type response with saHBEC. Normal or asthmatic status of HBEC differentially shapes the epithelial-dendritic responses. We conclude that control moDC cannot rescue the hyperresponsive airway epithelium of severe asthmatics

Streamlining basophil activation testing to enable assay miniaturization and automation of sample preparation

Background: Numerous studies have demonstrated the capabilities of the basophil activation test (BAT) but various parameters such as a lack of standardization and a time consuming and labor intensive workflow continue to hinder the field to fully leverage the capabilities of this technique. When pediatric patients have to be considered, an additional limitation is related to blood volume consumption. Objectives: This work aimed at developing and characterizing a simplified and standardized whole-blood based BAT prototype procedure and at further assessing the feasibility of automating and miniaturizing the developed assay into a 96 well plate format. Methods: A dry and room temperature stable reagent technology was used to simplify and standardize BAT. Under optimized conditions, EDTA anticoagulated whole blood samples of non-allergic and allergic donors ( < 24 h old) together with calcium containing buffer were added to ready-to-use dry reagent tubes or 96 well plates (negative controls, positive controls and allergen tests) containing a 5 color compensation-free antibody panel (CD45-KrO/CD3-PC7/CRTH2-A647/CD203c-PE/CD63-PB). Upon mixing and incubation at 37 degrees C for 15 min, erythrocytes were lysed and samples were analyzed by flow cytometry without further washing steps. While it is important to precisely control the incubation time to minimize the assay variability, herein, a 15 min incubation time was chosen as it provides a suitable compromise for both the magnitude of basophil activation and the quality of the staining. A Biomek NXP robotic platform (Beckman Coulter) was used for automation and both CD203c and CD63 levels were monitored to characterize basophil reactivity. Results: This streamlined BAT protocol is no-wash, compensation free and only requires 4 pipetting steps to be completed. The assessment of assay performance characteristics showed wide applicability, satisfactory repeatability and a high degree of standardization as demonstrated by very low infra-assay and inter-operator variabilities (CVs < 10%). Leveraging these technical foundations, it was then proven that this new BAT procedure can easily be transposed into the 96 well plate format, thereby benefiting from a miniaturized format and full automation capabilities. When considering 8 dilution points to characterize the ex vivo basophil reactivity of a given whole blood sample, we found that as little as 51.1.L of blood per point could be used. Conclusions: A whole blood based and simplified procedure for BAT is proposed. It relies on a dry antibody formulation technology and requires only a few manual steps to be completed. This procedure can also be transposed in a 96 well plate format, fully automated and miniaturized, when sample volume reduction, throughput increase or unattended sample preparation is required

Responses of microbial degradation patterns of soil organic matter to a gradient of anthropogenic pressure on agrosystems

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