Macrophage-matrix interactions: orchestrating the fibrotic response?

Even though years of research have advanced our understanding of idiopathic pulmonary fibrosis (IPF), the expanded knowledge on risk factors and mechanisms has not yet resulted in effective treatments to control or cure this disease. In patients with IPF, an aberrant wound healing response results in an extracellular matrix (ECM) with altered biochemical and biophysical properties. As key regulators of the wound healing response, macrophages should be able to prevent or resolve fibrosis by regulating the production and degradation of ECM proteins. However, the impact of direct interactions between (fibrotic) matrix and macrophages on the macrophages’ ability to orchestrate the wound healing response is still unclear, and therefore the focus of this thesis. A collagen type I-based in vitro model was developed to study the response of alveolar-like macrophages to collagen layers with varying morphology and stiffness. Macrophages were found to change their shape, behavior, and marker expression depending on the morphology of the collagen they were cultured on. To connect the in vitro effect of different collagen morphologies with the in vivo situation, the amount of structurally disrupted collagen was visualized in lung tissue from patients with IPF and controls. Higher levels of structurally disrupted collagen were found in patients with IPF, indicating that extensive collagen remodeling is taking place. Furthermore, to improve our understanding of macrophage polarization, an optical tweezers-based system was used to study macrophage activation upon a single biochemical stimulus on a single-cell level with very high spatiotemporal resolution. In conclusion, it is without doubt that macrophages are able to sense changes in their microenvironment and subsequently change their phenotype. However, a better understanding of fibrosis-related ECM changes and functional macrophage polarization is required to clarify the exact role of macrophage-matrix interactions in orchestrating the fibrotic response

Mauvais sang : le corps effusif dans le cinéma de Patrice Chéreau

Nul n’ignore que l’intimité constitue le cœur du cinéma de Patrice Chéreau. Mais c’est un cœur qui bat à se rompre dès qu’il s’expose à l’état de symptôme. Chez lui, l’intimité est ce qui relève de l’extériorisation subversive du négatif, elle n’est filmable que dans l’expression d’un débordement des limites corporelles. C’est par l’excès qu’elle se manifeste. Il n’est donc pas rare de voir couler le sang pour la mettre en alerte et la faire jaillir au contact du monde extérieur, jusqu’à soumettre celui-ci à sa temporalité et à sa force. Patrice Chéreau fait du sang la marque la plus aiguë de la littéralité somatique, le moment où le corps se déchire sous la pression trop forte d’une intimité trahie par le retour souvent malveillant du dehors. À chaque fois qu’un corps saigne, il figure à l’extrême une émotivité à proportion d’un réel qui, après avoir été mis à distance, revient s’immiscer dans les veines tel un poison.Everybody knows that intimacy is the heart of Patrice Chéreau’s cinema. But this heart is beating wildly whenever it is exposed as a symptom. For him, intimacy is the subversive exteriorisation of the negative, it can only be shot with the overflowing of corporal limits. Excess is its form of expression. Therefore blood is often flowing so intimacy can be in a state of alert and arise at the contact of the outside world until the outside world is submitted to its temporality and to its strength. To Patrice Chéreau, blood is the sharpest sign of the somatic literality: the body is torn under the pressure of a betrayed intimacy, betrayed because of the – often evil – element coming back from the outside. Whenever a body bleeds, an extreme emotivity is represented to the proportion of a reality which, after having been kept in the distance, returns like a poison that runs through the veins

Contempler sauve

Voilà, cher Socrate, dit L’Étrangère de Mantinée, quel est le point de la vie où, autant qu’en aucun autre imaginable, il vaut pour un homme la peine de vivre : quand il contemple la beauté en elle-même.Platon, Le Banquet. Le cinéma de Jean-Claude Brisseau se mérite à hauteur de la lutte qu’il emporte obstinément. Tout en effet n’y est que lutte : des classes, du maître et de l’ignorant, de l’obscurité et de la lumière, de l’esprit et de..

Une table à l’Élysée

Le projet du Pouvoir (2013), documentaire réalisé par Patrick Rotman, jouit en apparence d’un privilège exceptionnel : obtenir l’accord de filmer à l’intérieur du Palais de l’Élysée pendant les huit premiers mois du quinquennat de François Hollande. Sous le contrôle de son auguste hôte, l’objectif du réalisateur n’est évidemment pas d’approcher les arcanes du pouvoir dans toute leur complexité mais bien de faire en sorte que cette proximité autorisée se confonde avec la familiarité de son lieu, que cette hospitalité inédite serve idéalement l’image d’un président autoproclamé « normal ». En suivant de près le comportement au quotidien du chef de l’État dans ses salons et bureaux, Rotman ne livre que des bouts de réalité du pouvoir à défaut d’en percer la vérité. Il ne filme alors qu’à travers le privilège qui lui a été fait d’assister aux privilèges immuables des dirigeants. Sans doute à son corps défendant, le film apporte sa contribution à la volonté de transparence revendiquée par François Hollande tout au long de sa campagne électorale. Mais tout voir signifie-t-il forcément tout comprendre ?Patrick Rotman’s documentary project for Le Pouvoir (Power) (2013) apparently benefited from a unique opportunity – the director-producer was allowed to film inside the Élysée Palace during the first eight months of François Hollande’s five-year term. Being under the supervision of his august host, the director’s objective was obviously not to tackle the mysteries of power in all their complexity but more to blend this authorised intimacy with the familiarity of the surroundings; this unusual hospitality being ideal to promote the image of a self-proclaimed “normal” President. Rotman, closely following the Head of State as he goes about his daily business in drawing-rooms, state-rooms and offices, only reveals titbits of the reality of power instead of getting to the “real truth”. He thus only films through the filter of the privilege given to him to witness the unchanging privileges of the rulers. Probably through no will of its maker, the documentary may have contributed to the call for transparency expressed by François Hollande throughout his election campaign. But does seeing everything necessarily mean understanding everything

Alain Badiou, Pierre Bourdieu, Judith Butler, Georges Didi-Huberman, Sadri Khiari, Jacques Rancière, Qu’est-ce qu’un peuple ?

En ces temps où diverses crises entrent en corrélation (crise économique, crise de sa gestion par l’État, crise de confiance dans l’action politique), cette récente livraison des éditions La Fabrique se propose de faire le point sur la notion polysémique de « peuple » et de ses dérivés (« populaire », « populisme », etc.). En six textes-fleuves signés de quelques auteurs « maison », l’ouvrage cherche clairement à extraire le mot « peuple » de sa réduction a..

Avant-propos

Cet avant-propos rappelle l’origine scientifique de la présente publication sur les liens tissés entre les grands auteurs de la Nouvelle Vague française des années 1960 et la lettre sous toutes ses formes (manuelle, transitionnelle, critique, littéraire, etc.). Constituée autour d’un cycle de journées d’études et d’un colloque organisés entre 2014 et 2021 à l’université de Caen Normandie par le laboratoire de recherche Laslar, cette origine met en lumière le projet d’aborder en une série d’approches variées (historique, esthétique, biographique, etc.), les différentes natures et projections de l’écrit dans l’inspiration et la pratique même des films de la Nouvelle Vague.This foreword recalls the scientific origin of the present publication on the links woven between the great authors of the French New Wave of the 1960s and the letter in all its forms (manual, transitional, critical, literary, etc.). Constituted around a cycle of study days and a colloquium organized between 2014 and 2021 at the University of Caen Normandie by the Laslar research laboratory, this origin highlights the project to address in a series of varied approaches (historical, aesthetic, biographical, etc.), the different natures and projections of the written word in the inspiration and the very practice of New Wave films

Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules

Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDA-MB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM of NaPa). As cell invasiveness is greatly influenced by the expression of urokinase (u-PA) and its cell surface receptor (u-PAR) as well as the secretion of matrix metalloproteinases (MMP), we tested the effect of NaPa on these parameters. An 18-hour incubation with NaPa did not modify u-PA expression, either on MDA-MB-231 or on MCF-7 and MCF-7 ras cell lines, and induced a small u-PA decrease after 3 days of treatment of MDA-MB-321 with NaPa. In contrast, an 18 h incubation of MDA-MB-231 increased the expression of u-PAR and the secretion of MMP-9. As u-PAR is a ligand for vitronectin, a composant of the extracellular matrix, these data could explain the increased adhesion of MDA-MB-231 to vitronectin, while cell adhesivity of MCF-7 and MCF-7 ras was unmodified by NaPa treatment. NaPa induced also an increased expression of both Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1), which was obvious from 18 hour incubation with NaPa for the MDA-MB-231 cells, but was delayed (3 days) for MCF-7 and MCF-7 ras. Only neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells. Therefore we can conclude that the strong inhibition of MDA-MB-231 invasiveness is not due to a decrease in proteases involved in cell migration (u-PA and MMP) but could be related both to the modification of cell structure and an increased expression of adhesion molecules such as u-PAR and LFA-1. © 2001 Cancer Research Campaign http://www.bjcancer.co

What Role for Angiogenesis in Childhood Acute Lymphoblastic Leukaemia?

The role of angiogenesis in acute leukaemia has been discussed since the cloning of the gene of vascular endothelial growth factor (VEGF) from the acute myelogenous leukemia cell line (HL60) and, thereafter, when the first studies reported increased bone marrow vascularity and elevation of angiogenic cytokines in acute lymphoblastic leukaemia (ALL). VEGF and basic fibroblast growth factor (bFGF) are the major proangiogenic cytokines that have been studied, and evaluation of their prognostic impact in childhood ALL has been reported in several studies, though with controversial results. The antiangiogenic response, contributing to the angiogenic balance, has scarcely been reported. The origin of the factors, their prognostic value, and their relevance as good markers of what really happens in the bone marrow are discussed in this paper. The place of antiangiogenic drugs in ALL has to be defined in the global treatment strategy

Avant-propos

Représentation et pouvoir sont de même nature. Que dit-on lorsque l’on dit pouvoir ? Pouvoir, c’est d’abord être en état d’exercer une action sur quelque chose ou quelqu’un ; non pas agir ou faire, mais en avoir la puissance, avoir cette force de faire ou d’agir. Puissance, le pouvoir est également et de surcroît valorisation de cette puissance comme contrainte obligatoire, génératrice de devoirs comme loi. En ce sens, pouvoir, c’est instituer ..

Plant Carbohydrate Scavenging through TonB-Dependent Receptors: A Feature Shared by Phytopathogenic and Aquatic Bacteria

TonB-dependent receptors (TBDRs) are outer membrane proteins mainly known for the active transport of iron siderophore complexes in Gram-negative bacteria. Analysis of the genome of the phytopathogenic bacterium Xanthomonas campestris pv. campestris (Xcc), predicts 72 TBDRs. Such an overrepresentation is common in Xanthomonas species but is limited to only a small number of bacteria. Here, we show that one Xcc TBDR transports sucrose with a very high affinity, suggesting that it might be a sucrose scavenger. This TBDR acts with an inner membrane transporter, an amylosucrase and a regulator to utilize sucrose, thus defining a new type of carbohydrate utilization locus, named CUT locus, involving a TBDR for the transport of substrate across the outer membrane. This sucrose CUT locus is required for full pathogenicity on Arabidopsis, showing its importance for the adaptation to host plants. A systematic analysis of Xcc TBDR genes and a genome context survey suggested that several Xcc TBDRs belong to other CUT loci involved in the utilization of various plant carbohydrates. Interestingly, several Xcc TBDRs and CUT loci are conserved in aquatic bacteria such as Caulobacter crescentus, Colwellia psychrerythraea, Saccharophagus degradans, Shewanella spp., Sphingomonas spp. or Pseudoalteromonas spp., which share the ability to degrade a wide variety of complex carbohydrates and display TBDR overrepresentation. We therefore propose that TBDR overrepresentation and the presence of CUT loci designate the ability to scavenge carbohydrates. Thus CUT loci, which seem to participate to the adaptation of phytopathogenic bacteria to their host plants, might also play a very important role in the biogeochemical cycling of plant-derived nutrients in marine environments. Moreover, the TBDRs and CUT loci identified in this study are clearly different from those characterized in the human gut symbiont Bacteroides thetaiotaomicron, which allow glycan foraging, suggesting a convergent evolution of TBDRs in Proteobacteria and Bacteroidetes