Formation of polarized contractile interfaces by self-organized Toll-8/Cirl GPCR asymmetry

International audienc

UFMylation of MRE11 is essential for telomere length maintenance and hematopoietic stem cell survival

International audienc

RESULTATS DE LA PROTHESE BIPOLAR* DANS LE TRAITEMENT DES ARTHROPATHIES DEGENERATIVES A COIFFE DETRUITE (A PROPOS DE 46 CAS)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Quantitative proteomic analysis exploring progression of colorectal cancer: Modulation of the serpin family

International audienceColorectal cancer (CRC) remains a major cause of cancer related-death in developed countries. The mortality risk is correlated with the stage of CRC determined at the primary diagnosis and early diagnosis is associated with enhanced survival rate. Currently, only faecal occult blood tests are used to screen for CRC. Consequently, there is an incentive to identify specific markers of CRC. We used quantitative proteomic analysis of serum samples to characterize protein profiles in adenoma, CRC and healthy control samples. We identified 89 distinct proteins modulated between normal, colorectal adenoma and carcinoma patients. This list emphasizes proteins involved in enzyme regulator activities and in particular the serpin family. In serum samples, protein profiles of three members of the serpin family (SERPINA1, SERPINA3 and SERPINC1) were confirmed by ELISA assays. We obtained sensitivity/specificity values of 95%/95% for both SERPINA1 and SERPINC1, and 95%/55% for SERPINA3. This study supports the idea that serum proteins can discriminate adenoma and CRC patients from unaffected patients and reveals a panel of regulated proteins that might be useful for selecting patients for colonoscopy. By evaluating SERPINA1, SERPINA3 and SERPINC1, we highlight the potential role of the serpin family during the development and progression of CRC

Propriétés interfaciales et moussantes de protéines globulaires laitières étuvées

National audienceEn plus de leurs propriétés nutritionnelles, les protéines laitières ont des propriétés fonctionnelles jouant un rôle essentiel dans l'appétence et la qualité organoleptique des aliments. En particulier, les protéines laitières ont des propriétés moussantes résultant de leur aptitude à s’adsorber rapidement à l’interface eau/air, se déployer à l’interface et former un film interfacial résistant mécaniquement. (1) L’auto-assemblage des protéines globulaires à l’interface et les propriétés mécaniques du film sont sensibles à leur structure. Des modifications structurales de faible ampleur, affectant peu la structure tertiaire, peuvent avoir d’importantes conséquences sur leurs propriétés interfaciales et sur leurs propriétés moussantes. (2) Notre objectif est d’étudier le lien entre la structure des protéines du lactosérum, leurs propriétés interfaciales et leurs propriétés moussantes. Ainsi, après avoir procédé à des modifications structurales de faible ampleur de protéines de lactosérum, nous étudions leurs propriétés moussantes. Nous travaillons sur un produit industriel laitier, un isolat de protéines sériques (WPI) et sur de la β-lactoglobuline purifiée (β-Lg), qui en est le principal constituant. Pour modifier la structure des protéines, nous effectuons un étuvage ou traitement thermique à sec. Ce procédé est connu pour améliorer les propriétés moussantes de protéines globulaires d'autres origines. (2) L’effet de différents paramètres d’étuvage sont étudiés : l’activité de l'eau de la poudre, le pH avant déshydratation et la durée de l’étuvage. Les agrégats solubles et insolubles, éventuellement générés, sont éliminés avant d’effectuer des analyses structurales et d’évaluer les propriétés moussantes. En particulier, du fait de la présence résiduelle de lactose dans le WPI, l'impact sur les propriétés moussantes d'une éventuelle lactosylation non enzymatique des protéines dans les conditions de l'étuvage est évalué, grâce à la comparaison avec la β-Lg purifiée. Les liens entre les modifications des propriétés moussantes et celles du comportement des protéines à l'interface eau-air seront discutés

How foam stability against drainage is affected by conditions of prior whey protein powder storage and dry-heating: A multidimensional experimental approach

International audienceIn the present work, we investigated the effects of powder dry-heating parameters on whey protein foams stability, especially against drainage.To this aim, whey protein isolate solutions were prepared at various pH (3.5, 5.0, 6.5), with or without a prior dialysis step to reduce the lactose content, freeze-dried, adjusted to various levels (0.12, 0.23, 0.52) of powder water activity aw and dry-heated at 70 °C for up to 125 h. Protein solutions were then reconstituted at pH 7.0 and foams prepared by air bubbling.An original approach was followed to study the foam stability against drainage, involving monitoring of the liquid fraction as a function of both height in the foam column and time, and analysing the whole set of time and height liquid fraction profiles using multivariate statistics.The effects of dry-heating parameters were markedly interdependent, resulting in complex effects on foam stability. However, the results suggest that dry-heating at pH 3.5 increased foam stability. Moreover, the aw adjustment step, though consisting in a two-week pre-conditioning at room temperature, also had a significant effect on the foam stability, of the same order of magnitude as dry-heating effects

Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway

The propagation and diversification of signals downstream of the T cell receptor (TCR) involve several adaptor proteins that control the assembly of multimolecular signaling complexes (signalosomes). The global characterization of changes in protein-protein interactions (PPI) following genetic perturbations is critical to understand the resulting phenotypes. Here, by combining genome editing techniques in T cells and interactomics studies based on affinity purification coupled to mass spectrometry (AP-MS) analysis, we determined and quantified the molecular reorganization of the SLP76 interactome resulting from the ablation of each of the three GRB2-family adaptors. Our data showed that the absence of GADS or GRB2 induces a major remodeling of the PPI network associated with SLP76 following TCR engagement. Unexpectedly, this PPI network rewiring minimally affects proximal molecular events of the TCR signaling pathway. Nevertheless, during prolonged TCR stimulation, GRB2- and GADS-deficient cells displayed a reduced level of activation and cytokine secretion capacity. Using the canonical SLP76 signalosome, this analysis highlights the plasticity of PPI networks and their reorganization following specific genetic perturbations

Dermal Fibroblast SLC3A2 Deficiency Leads to Premature Aging and Loss of Epithelial Homeostasis

Skin homeostasis relies on fine-tuning of epidermis-dermis interactions and is affected by aging. While extracellular matrix (ECM) proteins, such as integrins, are involved in aging, the molecular basis of the skin changes needs to be investigated further. Here, we showed that integrin co-receptor, SLC3A2, required for cell proliferation, is expressed at the surface of resting dermal fibroblasts in young patients and is reduced drastically with aging. In vivo SLC3A2 dermal fibroblast deletion induced major skin phenotypes resembling premature aging. Knockout mice (3 months old) presented strong defects in skin elasticity due to altered ECM assembly, which impairs epidermal homeostasis. SLC3A2 dermal fibroblast loss led to an age-associated secretome profile, with 77% of identified proteins belonging to ECM and ECM-associated proteins. ECM not only contributes to skin mechanical properties, but it is also a reservoir of growth factors and bioactive molecules. We demonstrate that dermal fibroblast SLC3A2 is required for ECM to fully exert its structural and reservoir role allowing proper and efficient TGF-beta localization and activation. We identified SLC3A2 as a protective controller of dermal ECM stiffness and quality required to maintain the epidermis to dermis interface as functional and dynamic

Transdermal Alcohol Measurements Using MOX Sensors in Clinical Trials

Human metabolism often results in the emission of many VOCs through the skin. Ethanol is one of volatile compounds which are evaporated by perspiration. The aim of our research consists to develop chemical sensors for monitoring ethanol emission after alcohol consumption. The interest of using chemical sensors is noninvasive measurement and controlling alcohol level in the human body and to make the link between these measurements and that in the blood or in the breath. Recent clinical trials demonstrated the feasibility and relevance of this measurement method. Metal oxide sensors were calibrated in respect of the thermodynamic conditions of the surface of the skin. In this paper we show the first sensor responses by perspiration

Ex vivo CSC assays for personalized testing of drug susceptibility in advanced breast cancer

San Antonio Breast Cancer Symposium, San Antonio, TX, DEC 05-09, 201