Cryosectioning the intestinal crypt-villus axis: An ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells

AbstractThe intestinal epithelium is a particularly attractive biological adult model to study epigenetic mechanisms driving adult stem cell renewal and cell differentiation. Since epigenetic modifications are dynamic, we have developed an original ex vivo approach to study the expression and epigenetic profiles of key genes associated with either intestinal cell pluripotency or differentiation by isolating cryosections of the intestinal crypt-villus axis. Gene expression, DNA methylation and histone modifications were studied by qRT-PCR, methylation-specific PCR and micro-chromatin immunoprecipitation, respectively. Using this approach, it was possible to identify segment-specific methylation and chromatin profiles. We show that (i) expression of intestinal stem cell markers (Lgr5, Ascl2) exclusively in the crypt is associated with active histone marks, (ii) promoters of all pluripotency genes studied and transcription factors involved in intestinal cell fate (Cdx2) harbour a bivalent chromatin pattern in the crypts and (iii) expression of differentiation markers (Muc2, Sox9) along the crypt-villus axis is associated with DNA methylation. Hence, using an original model of cryosectioning along the crypt-villus axis that allows in situ detection of dynamic epigenetic modifications, we demonstrate that regulation of pluripotency and differentiation markers in healthy intestinal mucosa involves different and specific epigenetic mechanisms

Assessment of the real contact area of a multi-contact interface from electrical measurements

The electrical supply of moving trains is provided by a sliding contact between the train's pantographs and the catenary. This electromechanical interface is composed of the pantograph's strips ? made mainly of carbon ? and the catenary contact wire. The temperature rising induces the rising of the carbon strip wear. Moreover, the heating produced at the interface depends on the surface quality. Indeed, the smaller is the surface contact, the greater is the electrical resistance which implies more heat production because of the Joule effect. The problem is multi-physical, there is a coupling between mechanical, electrical and thermal states. The objective is to define the real contact area with a simple electrical measurement. In many practical or fundamental situations involving contacting solids, the relevant notion of the real contact area is a very delicate one and especially its experimental assessment. Based on the Drude's classical transport model and within the linear elasticity approximation, a phenomenological model of a metal/metal contact is built up, offering a simplified interpretation framework of experimental data. The model accounts for the influence of the mechanical state of the contacting zone upon its electrical properties, such as its impedance. Interpreting available data within this framework leads to the assessment of the spots' number. The total contact force works on the spots and on the average contact length. In this model, the interface is treated as a new medium with its own conductivity and mean free time between ionic collisions. There are two types of measurement: - Electrical measurements carried out on two copper sheets with dimensions 50X50X1 mm3 acted upon with an external compression force, allowed to check and validate the model. In agreement with the conditions of the model and to avoid the complexification of the model due to the intricacy between thermal and electrical processes at the contact interface, the measurements were operated in alternative current at low voltages. - Additional measurements of surface states have been realized to join the electrical measure with roughness and the nature of the metal.  In the case of contact between train's pantograph and catenary, this method allows predicting electric transfer's quality to control the heating of the interface. Being sensitive to the spots' mechanical solicitation conditions, properly interpreted, electrical impedance measurements should lead to a better understanding of the complex mechanical responses of these interfaces and their ageing process or even to detect a fatigue and prevent a potential failure

MUC4 dans la résistance aux traitements chimiothérapeutiques et voies de signalisations associées

National audienc

Roles of MUC4 mucin and ErbB2 receptor in pancreatic carcinogenesis and chemoresistance.

International audienc

MUC4 oncomucin and pancreatic carcinogenesis: The NeverEnding Story

International audienc

Analyse des divergences économiques au sein de la zone euro: conséquences pour le futur de la zone monétaire

Le but de ce mémoire est de répondre à la question suivante: les divergences économiques au sein de la zone euro sont-elles telles qu'une séparation de la zone euro est une meilleure issue que le maintien de l'euro? Afin d'y répondre, nous faisons le point sur les bénéfices procurés par la zone euro ainsi que l'évolution de la gouvernance au sein de celle-ci dans un premier temps. Ensuite nous analysons les divergences au sein de la zone à l'aide d'une forme générale de la théorie de la zone monétaire optimale. Dans la troisième partie nous vérifions l'incidence de ces divergences sur l'efficacité de la politique monétaire. Enfin nous formulons nos recommandations pour garantir le futur de la zone euro.Master [120] en sciences économiques, orientation générale, Université catholique de Louvain, 201

Mucins and tumor resistance to chemotherapeutic drugs

International audienceEpithelial cancer patients not considered eligible for surgical resection frequently benefit from chemotherapy. Chemotherapy is the treatment of cancer with one or combination of cytotoxic or cytostatic drugs. Recent advances in chemotherapy allowed a great number of cancer patients to receive treatment with significant results. Unfortunately, resistance to chemotherapeutic drug treatment is a major challenge for clinicians in the majority of epithelial cancers because it is responsible for the inefficiency of therapies. Mucins belong to a heterogeneous group of large O-glycoproteins that can be either secreted or membrane-bound. Implications of mucins have been described in relation to cancer cell behavior and cell signaling pathways associated with epithelial tumorigenesis. Because of the frequent alteration of the pattern of mucin expression in cancers as well as their structural and functional characteristics, mucins are thought to also be involved in response to therapies. In this report, we review the roles of mucins in chemoresistance and the associated underlying molecular mechanisms (physical barrier, resistance to apoptosis, drug metabolism, cell stemness, epithelial-mesenchymal transition) and discuss the therapeutic tools/strategies and/or prognosis biomarkers for personalized chemotherapy that could be proposed from these studies

figure intestin schema.ai

<p>Schematic representation of villus-crypt axis in intestinal epithelium</p

The Membrane-Bound Mucins: How Large O-Glycoproteins Play Key Roles in Epithelial Cancers and Hold Promise as Biological Tools for Gene-Based and Immunotherapies

International audienceMembrane-bound mucins belong to an ever-increasing family of O-glycopro-teins that share a structure conserved throughout evolution. Typically, membrane-bound mu-cins contain a long extracellular domain, a hydrophobic transmembrane domain, and a short cytoplasmic tail. They are modular proteins and have a structural organization containing Pro/ Thr/Ser-rich O-glycosylated domains and EGF-like domains. The biological roles of mucins arise from their structures. MUC1 and MUC4 modulate biological properties of the cell, alter its behavior and modulate cell signaling pathways associated with tumorigenesis. Altered expression and post-translational modifi cations confer an important role to MUC1 and MUC4 in tumor progression, metastasis, and cancer cell chimioresistance. Moreover, increasing knowledge about their animal counterparts has made possible a greater understanding of their pathophysiological role in vivo. Most biological functions attributed to MUC4 are based on the structural homology with its rat homologue. From these results, the development of new biological tools targeting mucins has been increasing and the recent attention given to these complex molecules may bring hope for improved cancer treatments in the future. This review discusses the structure/function of MUC1 and MUC4 membrane-bound mucins in relation to cancer cell behavior and cell signaling pathways associated with tumorigenesis, as well as their potential as biological tools for gene therapy and immunotherapy approaches

Fine-tuning autophagy in pancreatic adenocarcinoma: full blockage is required

International audienc