The human gene encoding uPAR (PLAUR) has been shown recently to be associated with the risk of autism. The uPAR(-/-) mouse exhibits a regionally-selective reduction in GABAergic interneurons in frontal and parietal regions of the cerebral cortex as well as in the CA1 and dentate gyrus subfields of the hippocampus. Behaviorally, these mice exhibit increased sensitivity to pharmacologically-induced seizures, heightened anxiety, and atypical

social behavior. Here, we explore find more potential alterations in GABAergic circuitry that may occur in the context of altered intemeuron development. Analysis of gene expression for 13 GABA(A) receptor subunits using quantitative real-time polymerase chain reaction (PCR) indicates seven subunit mRNAs (alpha(1), alpha(2), alpha(3), beta(2), beta(3), gamma(2S) and gamma(2L)) of interest. Semi-quantitative in situ hybridization analysis focusing selleck chemical on these subunit mRNAs reveals a complex pattern of potential gene regulatory adaptations. The levels of alpha(2) subunit mRNAs increase in frontal cortex, CA1 and CA3, while those of alpha(3) decrease in frontal cortex and CA1. In contrast, alpha(1) subunit mRNAs are unaltered in any region examined. beta(2) subunit mRNAs are increased in frontal cortex whereas beta(3) subunit mRNAs are decreased in parietal

cortex. Finally, gamma(2S) subunit mRNAs are increased in parietal cortex

while gamma(2L) subunit mRNAs are increased in the dentate gyrus, potentially altering the gamma(2S):gamma(2L) ratio in these two regions. For all subunits, no changes were observed in forebrain Prexasertib regions where GABAergic interneuron numbers are normal. We propose that disrupted differentiation of GABAergic neurons specifically in frontal and parietal cortices leads to regionally-selective alterations in local circuitry and subsequent adaptive changes in receptor subunit composition. Future electrophysiological studies will be useful in determining how alterations in network activity in the cortex and hippocampus relate to the observed behavioral phenotype. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Hepatitis C virus (HCV) is a liver-tropic pathogen with severe health consequences for infected individuals. Chronic HCV infection can progress to cirrhosis and hepatocellular carcinoma and is a leading indicator for liver transplantation. The HCV core protein is an essential component of the infectious virus particle, but many aspects of its role remain undefined. The C-terminal region of the core protein acts as a signal sequence for the E1 glycoprotein and undergoes dual processing events during infectious virus assembly. The exact C terminus of the mature, virion-associated core protein is not known.