Z-disc protein CHAPb induces cardiomyopathy and contractile dysfunction in the postnatal heart

The Z-disc is a crucial structure of the sarcomere and is implicated in mechanosensation/transduction. Dysregulation of Z-disc proteins often result in cardiomyopathy. We have previously shown that the Z-disc protein Cytoskeletal Heart-enriched Actin-associated Protein (CHAP) is essential for cardiac and skeletal muscle development. Furthermore, the CHAP gene has been associated with atrial fibrillation in humans. Here, we studied the misregulated expression of CHAP isoforms in heart disease. Mice that underwent transverse aortic constriction and calcineurin transgenic (Tg) mice, both models of experimental heart failure, displayed a significant increase in cardiac expression of fetal isoform CHAPb. To investigate whether increased expression of CHAPb postnatally is sufficient to induce cardiomyopathy, we generated CHAPb Tg mice under the control of the cardiac-specific αMHC promoter. CHAPb Tg mice displayed cardiac hypertrophy, interstitial fibrosis and enlargement of the left atrium at three months, which was more pronounced at the age of six months. Hypertrophy and fibrosis were confirmed by evidence of activation of the hypertrophic gene program (Nppa, Nppb, Myh7) and increased collagen expression, respectively. Connexin40 and 43 were downregulated in the left atrium, which was associated with delayed atrioventricular conduction. Tg hearts displayed both systolic and diastolic dysfunction partly caused by impaired sarcomere function evident from a reduced force generating capacity of single cardiomyocytes. This co-incided with activation of the actin signalling pathway leading to the formation of stress fibers. This study demonstrated that the fetal isoform CHAPb initiates progression towards cardiac hypertrophy, which is accompanied by delayed atrioventricular conduction and diastolic dysfunction. Moreover, CHAP may be a novel therapeutic target or candidate gene for screening in cardiomyopathies and atrial fibrillatio

Harmful Elements in Estuarine and Coastal Systems

Estuaries and coastal zones are dynamic transitional systems which provide many economic and ecological benefits to humans, but also are an ideal habitat for other organisms as well. These areas are becoming contaminated by various anthropogenic activities due to a quick economic growth and urbanization. This chapter explores the sources, chemical speciation, sediment accumulation and removal mechanisms of the harmful elements in estuarine and coastal seawaters. It also describes the effects of toxic elements on aquatic flora and fauna. Finally, the toxic element pollution of the Venice Lagoon, a transitional water body located in the northeastern part of Italy, is discussed as a case study, by presenting the procedures adopted to measure the extent of the pollution, the impacts on organisms and the restoration activities

Etude cinématique de la rupture sismique en champ lointain (méthodes et résolution)

Cette thèse décrit la cinématique de la source sismique, principalement à partir de données lointaines. Nous combinons l'usage des ondes de volumes et de surface et considérons à la fois une modélisation déterministe de la propagation (à partir des modèles de Terre) et une modélisation empirique (fournie par un véritable séisme, "fonction de Green empirique"). Deux situations sont alors envisagées: soit l'on s'intéresse à un séisme précis (1), soit l'on recherche des méthodes quasi-automatiques pour étudier la séismicité mondiale (2). L'approche (1) est appliquée au séisme d'El Salvador (13/01/2001, Mw=7.7). L'approche (2) nous conduit à décrire la faille sismique comme un ensemble fini de zones de glissement. La pertinence de cette méthode est illustrée au travers des séismes d'Izmit (Turquie, 1999) et de Jalisco (Mexique, 1955). Une nouvelle technique d'analyse par fonction de Green empirique est développée et plus spécifiquement appliquée au séisme du Pérou du 23/06/2001 (Mw=8.4).GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Observation of Long Supershear Rupture During the Magnitude 8.1 Kunlunshan Earthquake

International audienceThe 2001 Kunlunshan earthquake was an extraordinary event that produced a 400-km-long surface rupture. Regional broadband recordings of this event provide an opportunity to accurately observe the speed at which a fault ruptures during an earthquake, which has important implications for seismic risk and for understanding earthquake physics. We determined that rupture propagated on the 400-km-long fault at an average speed of 3.7 to 3.9 km/s, which exceeds the shear velocity of the brittle part of the crust. Rupture started at sub–Rayleigh wave velocity and became supershear, probably approaching 5 km/s, after about 100 km of propagation

Conception d'un outil de débogage formel pour systèmes logiciels et matériels selon l'approche "Debug as Design"

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF