1D and 3D heterogeneous

virtual tissues are constructed, with detailed tissue architecture (anisotropy and orthotropy, due to fibre orientation and sheet structure) of the left ventricular wall wedge extracted from a diffusion tensor imaging data set. The models are used to study the effects of tissue heterogeneity and class III drugs on transmural propagation LEE011 and tissue vulnerability to re-entry.\n\nWe have determined relationships between the transmural dispersion of action potential duration (APD) and the vulnerable window in the 1D virtual ventricular wall, and demonstrated how changes in the transmural heterogeneity, and hence tissue vulnerability, can lead to generation selleck chemical of re-entry in the 3D ventricular wedge. Two class III drugs with opposite qualitative effects on transmural APD heterogeneity are considered: d-sotalol that increases transmural APD dispersion, and amiodarone that decreases it. Simulations with the 1D virtual ventricular wall show that under d-sotalol conditions the vulnerable window is substantially wider compared to amiodarone

conditions, primarily in the epicardial region where unidirectional conduction block persists until the adjacent M cells are fully repolarised.\n\nFurther simulations with the 3D ventricular wedge have shown that ectopic stimulation of the epicardial region results in generation of sustained re-entry under d-sotalol conditions, but learn more not under amiodarone conditions or in control. Again, APD increase in M cells was

identified as the major contributor to tissue vulnerability-re-en try was initiated primarily due to ectopic excitation propagating around the unidirectional conduction block in the M cell region. This suggests an electrophysiological mechanism for the anti- and proarrhythmic effects of the class III drugs: the relative safety of amiodarone in comparison to d-sotalol can be explained by relatively low transmural APD dispersion, and hence, a narrow vulnerable window and low probability of re-entry in the tissue. (C) 2007 Elsevier Ltd. All rights reserved.”
“The nonstructural protein NS5A has emerged as a new drug target in antiviral therapies for Hepatitis C Virus (HCV) infection. NS5A is critically involved in viral RNA replication that takes place at newly formed membranes within the endoplasmic reticulum (membranous web) and assists viral assembly in the close vicinity of lipid droplets (LDs). To identify host proteins that interact with NS5A, we performed a yeast two-hybrid screen with the N-terminus of NS5A (amino acids 1-31), a well-studied alpha-helical domain important for the membrane tethering of NS5A. Our studies identified the LD-associated host protein, Tail-Interacting Protein 47 (TIP47) as a novel NS5A interaction partner.