The Src Homology and Collagen A (ShcA) adaptor protein is required for the spatial organization of the costamere/Z-disk network during heart development

ShcA (Src Homology and Collagen A) is an adaptor protein that binds to tyrosine kinase receptors. Its germ line deletion is embryonic lethal with abnormal cardiovascular system formation, and its role in cardiovascular development is unknown. To investigate its functional role in cardiovascular development in mice, ShcA was deleted in cardiomyocytes and vascular smooth muscle cells by crossing ShcA flox mice with SM22a-Cre transgenic mice. Conditional mutant mice developed signs of severe dilated cardiomyopathy, myocardial infarctions, and premature death. No evidence of a vascular contribution to the phenotype was observed. Histological analysis of the heart revealed aberrant sarcomeric Z-disk and M-band structures, and misalignments of T-tubules with Z-disks. We find that not only the ErbB3/Neuregulin signaling pathway but also the baroreceptor reflex response, which have been functionally associated, are altered in the mutant mice. We further demonstrate that ShcA interacts with Caveolin-1 and the costameric protein plasma membrane Ca2+/calmodulin-dependent ATPase (PMCA), and that its deletion leads to abnormal dystrophin signaling. Collectively, these results demonstrate that ShcA interacts with crucial proteins and pathways that link Z-disk and costamere

Role of Lipids in Spheroidal High Density Lipoproteins

We study the structure and dynamics of spherical high density lipoprotein (HDL) particles through coarse-grained multi-microsecond molecular dynamics simulations. We simulate both a lipid droplet without the apolipoprotein A-I (apoA-I) and the full HDL particle including two apoA-I molecules surrounding the lipid compartment. The present models are the first ones among computational studies where the size and lipid composition of HDL are realistic, corresponding to human serum HDL. We focus on the role of lipids in HDL structure and dynamics. Particular attention is paid to the assembly of lipids and the influence of lipid-protein interactions on HDL properties. We find that the properties of lipids depend significantly on their location in the particle (core, intermediate region, surface). Unlike the hydrophobic core, the intermediate and surface regions are characterized by prominent conformational lipid order. Yet, not only the conformations but also the dynamics of lipids are found to be distinctly different in the different regions of HDL, highlighting the importance of dynamics in considering the functionalization of HDL. The structure of the lipid droplet close to the HDL-water interface is altered by the presence of apoA-Is, with most prominent changes being observed for cholesterol and polar lipids. For cholesterol, slow trafficking between the surface layer and the regimes underneath is observed. The lipid-protein interactions are strongest for cholesterol, in particular its interaction with hydrophobic residues of apoA-I. Our results reveal that not only hydrophobicity but also conformational entropy of the molecules are the driving forces in the formation of HDL structure. The results provide the first detailed structural model for HDL and its dynamics with and without apoA-I, and indicate how the interplay and competition between entropy and detailed interactions may be used in nanoparticle and drug design through self-assembly

Mesure selective des temps de relaxation T2 des lipides intra et extramyocytaires chez le rat Zucker a 7 teslas

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Alveolar oxygen partial pressure and O2 depletion rate mapping in rats using 3He ventilation imaging

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Role of Exercise-Induced Oxidative Stress in Sickle Cell Trait and Disease

International audienceSickle cell disease is a class of hemoglobinopathy in humans, which is the most common inherited disease in the world. Although complications of sickle cell disease start from polymerization of red blood cells during its deoxygenating phase, the oxidative stress resulting from the biological processes associated with this disease (ischaemic and hypoxic injuries, hemolysis and inflammation) has been shown to contribute to its pathophysiology. It is widely known that chronic exercise reduces oxidative stress in healthy people, mainly via improvement of antioxidant enzyme efficiency. In addition, recent studies in other diseases, as well as in sickle cell trait carriers and in a mouse model of sickle cell disease, have shown that regular physical activity could decrease oxidative stress. The purpose of this review is to summarize the role of oxidative stress in sickle cell disease and the effects of acute and chronic exercise on the pro-oxidant/antioxidant balance in sickle cell trait and sickle cell disease

Retrospective Cine 3He ventilation imaging under spontaneous breathing conditions: a non invasive imaging protocol for small animal lung function imaging

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Modified EKG-triggered black-blood turbo spin-echo technique to improve T1-weighting in contrast-enhanced MRI of atherosclerotic carotid arteries

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Retrospective Cine ventilation imaging under spontaneous breathing conditions: a non invasive imaging protocol for rat lung function assessment

International audienc

Retrospective Cine 3He ventilation imaging under spontaneous breathing conditions: a non-invasive protocol for small animal lung function imaging

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In vivo quantification of regional myocardial blood flow: Validity of the fast exchange approximation for intravascular T1 contrast agent and long inversion time

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