Evolution respiratoire des grands prématurés issus de grossesses simples et multiples

La dysplasie broncho-pulmonaire (BPD) représente la complication pulmonaire principale des nouveau-nés prématurés. Il s'agit d'une pathologie chronique dont les causes sont multiples, mais souvent liées à la ventilation et l'oxygénothérapie dans les premiers jours de vie [1, 2, 3]. Elle peut toutefois apparaître chez des enfants présentant initialement relativement peu de difficultés respiratoires [4]. L'amélioration de la prise en charge des nouveau-nés prématurés au cours des dernières années a amené à une meilleure survie des grands prématurés de moins de 32 semaines d'âge gestationnel (very preterm (VP)) et de très petit poids de naissance de moins de 1.5 kg (very low birth weight (VLBW)) [2]. Malgré une mortalité à la baisse, l'incidence de la BPD est restée plus ou moins constante même si les complications graves chez les survivants sont à la baisse [5]. L'incidence de la BPD chez les nouveau-nés VP et VLBW est inversement proportionnelle à l'âge gestationnel et au poids de naissance ; elle était de 13% en Suisse en l'an 2000 [6]. Le nombre de grossesses gémellaires (GG) est en augmentation constante au vu de l'âge croissant des mères et le recours de plus en plus fréquent à la procréation médicalement assistée (PMA). Les GG représentent un facteur de risque important pour une naissance prématurée et un petit poids de naissance. La gémellarité peut alors également être considérée comme un facteur de risque pour la BPD et présente un intérêt tout à fait particulier dans l'étude de cette dernière. En effet, des jumeaux au sein d'une fratrie auront été exposés au même environnement et partageront un génome similaire, voire identique lors de grossesses monozygotiques. Il sera donc intéressant de voir si les enfants au sein d'une même fratrie auront un risque similaire ou non de développer une BPD

Paracrine crosstalk between endothelial cells and cardiomyocytes during inflammation

Endothelial cells (EC) release paracrine factors which can modulate the survival, morphology, and function of neighbouring cardiomyocytes (CM), e.g. contraction and relaxation. In multiple cardiomyopathies, as well as in heart failure, EC dysfunction correlates strongly with severity and prognosis, and moreover, endothelial inflammation is thought to precede this dysfunction. While it is known that EC functions are modified by inflammation, the paracrine effects of this response on neighbouring CM are poorly understood and too often confused with those of endothelial dysfunction. I hypothesised that calcium handling and contractile properties of CM were differently regulated by inflamed EC. To investigate this, a co-culture system was first validated as a model of the paracrine EC-CM crosstalk. A pro-inflammatory cocktail of TNFα, IL-1β and hIL-6 (“Cytomix”) was then validated as a pre-conditioning treatment for cardiac microvascular EC. Adult ventricular CM were co-cultured with untreated or Cytomix-treated EC. Calcium transients were then analysed in CM using Fluo-4 and Fura-2. Cell contractility and relaxation were also studied using an automated CytoCypher™ system. Finally, living rat myocardial slices were used to investigate the effects of Cytomix in a more complex heterocellular model. Co-culture with Cytomix-treated EC induced a significant shortening of calcium transients in CM compared to untreated EC (thus validating the hypothesis). This was due to an increase in SERCA activity. However, the cell shortening amplitude and rate of relaxation were unaffected by co-culture or Cytomix treatment, while data also suggests that the myofilament sensitivity to calcium was unchanged. In cultured myocardial slices, Cytomix treatment increased force but not the passive tension, although this was limited to high levels of stretch and kinetics were unchanged compared to untreated slices. Further work is required to better define and understand these mechanisms. This could help determine the therapeutic potential of controlling EC function in inflammatory heart diseases.Open Acces

Marché du travail, formation et fabrique de la tradition chez les compagnons tailleurs de pierre

L’Association Ouvrière des Compagnons du Devoir qui fédère diverses corporations, ne cesse de rationaliser la formation compagnonnique et d’organiser les formes et les structures du « tour de France ». Etant reconnue d’utilité publique et recevant des subventions de l’Etat, elle s’adapte aux contraintes de formation imposées par la législation française et aux évolutions connues dans le monde du travail. Les responsables de cette société compagnonnique ont mis en place de nouveaux projets de formation afin de promouvoir les métiers dits manuels et de perpétuer le compagnonnage. Ces projets génèrent des tensions et des conflits entre le conseil du compagnonnage et certains compagnons tailleurs de pierre. Cette situation conflictuelle peut permettre de lire la reconfiguration des hiérarchies compagnonniques ainsi que la hiérarchisation des valeurs construite par les compagnons tailleurs de pierre. Elle amène à réfléchir sur les interprétations, les usages et la fabrication de la tradition compagnonnique.The Craftsmen's Trade Guild (Association Ouvrière des Compagnons du Devoir) which federates various professions, constantly rationalizes guild training and organises the form and structure of the « tour de France ». Being state-approved and receiving State grants, the Guild has to adapt itself to the training restrictions imposed by French legislation and to developments in the professional world. Those in charge of this trade guild community have set up new training projects in order to promote what are known as manual occupations and to perpetuate the trade guild. These projects have created tensions and conflicts between the guild council and certain craftsmen stone-cutters. This conflictual situation enables us to perceive the reshaping of the guild environment as well as the organising into a hierarchy of the values built up by the craftsmen stone-cutters. It leads us to reflect upon the interpretations, the customs and the making of the guild tradition

Surface science and catalysis studies of the structure and reactivity of model catalysts

In this thesis, the structure and reactivity of palladium on titania has been studied on high surface area powdered materials and on low surface area models. Mathematical models have been established which relate the particle radius to various parameters such as particle surface area, density of particles, interparticle distance and coverage. The sintering process is studied through STM imaging and particle size distribution (PSD) calculation on two models. The technique resulting in PSD consists in the calculation of the particle density as a function of 4 parameters: perimeter, area, height and volume of the particle. This is done through the analysing of STM images using a build-in-house software. It is found that Cu followed the Ostwald ripening process while Pd followed the coalescence sintering. From the analysis of the Auger spectra, the growth mode of Cu and Pd were found to follow the Volmer -Weber mode consisting of 3D particle growth. The structure of the Pd/Ti02 system is investigated via STM and LEED analysis. It is shown that Pd nanoparticles supported TiC>2 reconstructed upon annealing into hexagonal, wagonwheel, star shape and zigzag superstructures. These various structures have unit cell dimensions varying from 9.5A to 25A and consist of mixed layer of titanium and palladium in their ground state. The possible structures are modelled and it is concluded that the Ti or Pd adatoms can be situated in atop, 2- or 3-fold sites. TPR results shows that CO uptake capacity is lost when the catalyst is reduced to high temperature. However, the CO oxidation reaction is enhanced. It is shown that encapsulation of Pd by TiOx species is responsible for the loss of CO adsorption but also for the improvement of the CO oxidation. Weakly bound forms of CO and new active centres, as a result of the reconstruction, can improve the activity of the CO oxidation reaction

Functional microvascularization of human myocardium in vitro

In this study, we report static and perfused models of human myocardial-microvascular interaction. In static culture, we observe distinct regulation of electrophysiology of human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) in co-culture with human cardiac microvascular endothelial cells (hCMVECs) and human left ventricular fibroblasts (hLVFBs), including modification of beating rate, action potential, calcium handling, and pro-arrhythmic substrate. Within a heart-on-a-chip model, we subject this three-dimensional (3D) co-culture to microfluidic perfusion and vasculogenic growth factors to induce spontaneous assembly of perfusable myocardial microvasculature. Live imaging of red blood cells within myocardial microvasculature reveals pulsatile flow generated by beating hiPSC-CMs. This study therefore demonstrates a functionally vascularized in vitro model of human myocardium with widespread potential applications in basic and translational research

Does the Integration of Haptic and Visual Cues Reduce the Effect of a Biased Visual Reference Frame on the Subjective Head Orientation?

The selection of appropriate frames of reference (FOR) is a key factor in the elaboration of spatial perception and the production of robust interaction with our environment. The extent to which we perceive the head axis orientation (subjective head orientation, SHO) with both accuracy and precision likely contributes to the efficiency of these spatial interactions. A first goal of this study was to investigate the relative contribution of both the visual and egocentric FOR (centre-of-mass) in the SHO processing. A second goal was to investigate humans' ability to process SHO in various sensory response modalities (visual, haptic and visuo-haptic), and the way they modify the reliance to either the visual or egocentric FORs. A third goal was to question whether subjects combined visual and haptic cues optimally to increase SHO certainty and to decrease the FORs disruption effect.Thirteen subjects were asked to indicate their SHO while the visual and/or egocentric FORs were deviated. Four results emerged from our study. First, visual rod settings to SHO were altered by the tilted visual frame but not by the egocentric FOR alteration, whereas no haptic settings alteration was observed whether due to the egocentric FOR alteration or the tilted visual frame. These results are modulated by individual analysis. Second, visual and egocentric FOR dependency appear to be negatively correlated. Third, the response modality enrichment appears to improve SHO. Fourth, several combination rules of the visuo-haptic cues such as the Maximum Likelihood Estimation (MLE), Winner-Take-All (WTA) or Unweighted Mean (UWM) rule seem to account for SHO improvements. However, the UWM rule seems to best account for the improvement of visuo-haptic estimates, especially in situations with high FOR incongruence. Finally, the data also indicated that FOR reliance resulted from the application of UWM rule. This was observed more particularly, in the visual dependent subject. Conclusions: Taken together, these findings emphasize the importance of identifying individual spatial FOR preferences to assess the efficiency of our interaction with the environment whilst performing spatial tasks

Identification of Keratinocyte Growth Factor as a Target of microRNA-155 in Lung Fibroblasts: Implication in Epithelial-Mesenchymal Interactions

International audienceBACKGROUND: Epithelial-mesenchymal interactions are critical in regulating many aspects of vertebrate embryo development, and for the maintenance of homeostatic equilibrium in adult tissues. The interactions between epithelium and mesenchyme are believed to be mediated by paracrine signals such as cytokines and extracellular matrix components secreted from fibroblasts that affect adjacent epithelia. In this study, we sought to identify the repertoire of microRNAs (miRNAs) in normal lung human fibroblasts and their potential regulation by the cytokines TNF-alpha, IL-1beta and TGF-beta. METHODOLOGY/PRINCIPAL FINDINGS: MiR-155 was significantly induced by inflammatory cytokines TNF-alpha and IL-1beta while it was down-regulated by TGF-beta. Ectopic expression of miR-155 in human fibroblasts induced modulation of a large set of genes related to "cell to cell signalling", "cell morphology" and "cellular movement". This was consistent with an induction of caspase-3 activity and with an increase in cell migration in fibroblasts tranfected with miR-155. Using different miRNA bioinformatic target prediction tools, we found a specific enrichment for miR-155 predicted targets among the population of down-regulated transcripts. Among fibroblast-selective targets, one interesting hit was keratinocyte growth factor (KGF, FGF-7), a member of the fibroblast growth factor (FGF) family, which owns two potential binding sites for miR-155 in its 3'-UTR. Luciferase assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Site-directed mutagenesis revealed that only one out of the 2 potential sites was truly functional. Functional in vitro assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Furthermore, in vivo experiments using a mouse model of lung fibrosis showed that miR-155 expression level was correlated with the degree of lung fibrosis. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest a physiological function of miR-155 in lung fibroblasts. Altogether, this study implicates this miRNA in the regulation by mesenchymal cells of surrounding lung epithelium, making it a potential key player during tissue injury