Crystallographic analysis of rock grain orientation at meso- and microscale levels

This paper studies the results of electron backscatter diffraction analysis of naturally deformedpolycrystalline olivine. It also defines the dependence of lattice-preferred orientations of grains on their microstructural position and size. The authors detect the basic mechanisms, consequence and thermal dynamic modes of deformation. They also show that the development of a polycrystalline structure is determined by the following consecutive activation of sliding systems (010)[100] → {0kl}[100] → (100)[010] → {100}[001] → {110}[001], when dislocation sliding and diffusion creep change under the temperature decrease from 1000°C to 650°C

Multiple Potential Molecular Contributors to Atrial Hypocontractility Caused by Atrial Tachycardia Remodeling in Dogs

Background-Atrial fibrillation impairs atrial contractility, inducing atrial stunning that promotes thromboembolic stroke. Action potential (AP)-prolonging drugs are reported to normalize atrial hypocontractility caused by atrial tachycardia remodeling (ATR). Here, we addressed the role of AP duration (APD) changes in ATR-induced hypocontractility. Methods and Results-ATR (7-day tachypacing) decreased APD (perforated patch recording) by approximate to 50%, atrial contractility (echocardiography, cardiomyocyte video edge detection), and [Ca2+](i) transients. ATR AP waveforms suppressed [Ca2+](i) transients and cell shortening of control cardiomyocytes; whereas control AP waveforms improved [Ca2+](i) transients and cell shortening in ATR cells. However, ATR cardiomyocytes clamped with the same control AP waveform had approximate to 60% smaller [Ca2+](i) transients and cell shortening than control cells. We therefore sought additional mechanisms of contractile impairment. Whole-cell voltage clamp revealed reduced I-CaL; I-CaL inhibition superimposed on ATR APs further suppressed [Ca2+](i) transients in control cells. Confocal microscopy indicated ATR-impaired propagation of the Ca2+ release signal to the cell center in association with loss of t-tubular structures. Myofilament function studies in skinned permeabilized cardiomyocytes showed altered Ca2+ sensitivity and force redevelopment in ATR, possibly due to hypophosphorylation of myosin-binding protein C and myosin light-chain protein 2a (immunoblot). Hypophosphorylation was related to multiple phosphorylation system abnormalities where protein kinase A regulatory subunits were downregulated, whereas autophosphorylation and expression of Ca2+-calmodulin-dependent protein kinase II delta and protein phosphatase 1 activity were enhanced. Recovery of [Ca2+](i) transients and cell shortening occurred in parallel after ATR cessation. Conclusions-Shortening of APD contributes to hypocontractility induced by 1-week ATR but accounts for it only partially. Additional contractility-suppressing mechanisms include I-CaL current reduction, impaired subcellular Ca2+ signal transmission, and altered myofilament function associated with abnormal myosin and myosin-associated protein phosphorylation. The complex mechanistic basis of the atrial hypocontractility associated with AF argues for upstream therapeutic targeting rather than interventions directed toward specific downstream pathophysiological derangements. (Circ Arrhythm Electrophysiol. 2010;3:530-541.

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Calciumkanaldichte in humanem ischämischen und reperfundierten, rechtsatrialen Myokardgewebe

Intracellular calcium overload is one of the major pathophysiological mechanisms contributing to myocardial ischemic injury. Two important calcium handling proteins responsible for the maintenance of an intracellular calcium homeostasis are the sarcolemmal voltage-gated L-type calcium channel (DHPR) and the sarcoplasmic reticulum calcium release channel (CRC). This study evaluated the density of both channels in human myocardium subjected to ischemia and reperfusion during cardia surgery. Biopsies of human right atria were collected during cardiac surgery: 1) before aortic cross-clamping (serving as controls, 2) during ischemia and 3) after reperfusion. DHPR and CRC densities were studied using radioligand binding. A 25% reduction in CRC density was found during ischemia and reperfusion. The calcium sensitivity of ryanodine binding to CRC was unchanged. DHPR density was unaltered during ischemia and reperfusion. A downregulation of CRC may lead to a defective release of Ca2+ from the sarcoplasmic reticulum which may lead to excitation-contraction uncoupling ultimately contributing to postischemic contractile dysfunction