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“Impulsivity and serotonergic neurotransmission have previously been shown to be linked to the intensity dependence of auditory evoked potentials. The present study investigates whether impulsivity in normal healthy subjects has a similar influence on the neuronal correlates of the coding of sound intensity using functional magnetic resonance imaging (fMRI). Forty-four participants completed Cloninger’s Tridimensional Personality Questionnaire (TPQ). The dependence of fMRI activation on sound intensity was examined using continuous pink noise with varying intensity

as acoustic stimuli. Imaging data were analyzed for the volume of activation sensitive to sound intensity. Impulsivity has a significant effect on the volume of activation sensitive to sound intensity. Persons with Proteases inhibitor high impulsivity scores on the TPQ scale show approximately CH5183284 order twice the volume of activation when compared with persons with low impulsivity scores. The neuronal correlate of impulsivity as revealed by fMRI gives strong evidence of a link between impulsive behavior and neural activity

evoked by auditory stimulation. This link may prove useful for measuring central serotonergic neurotransmission in a clinical setting. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“The replication of the hepatitis C viral (HCV) genome is accomplished by the NS5B RNA-dependent RNA polymerase (RdRp), for which mechanistic understanding and structure-guided drug design efforts have been hampered by its propensity to crystallize in a closed, polymerization-incompetent state. The removal of an autoinhibitory beta-hairpin loop from genotype 2a HCV NS5B increases learn more de novo RNA synthesis by >100-fold, promotes RNA binding, and facilitated the determination of the first crystallographic

structures of HCV polymerase in complex with RNA primer-template pairs. These crystal structures demonstrate the structural realignment required for primer-template recognition and elongation, provide new insights into HCV RNA synthesis at the molecular level, and may prove useful in the structure-based design of novel antiviral compounds. Additionally, our approach for obtaining the RNA primer-template-bound structure of HCV polymerase may be generally applicable to solving RNA-bound complexes for other viral RdRps that contain similar regulatory beta-hairpin loops, including bovine viral diarrhea virus, dengue virus, and West Nile virus.”
“The abuse of psychoactive ‘bath salts’ containing cathinones such as 3,4-methylenedioxypyrovalerone (MDPV) is a growing public health concern, yet little is known about their pharmacology. Here, we evaluated the effects of MDPV and related drugs using molecular, cellular, and whole-animal methods. In vitro transporter assays were performed in rat brain synaptosomes and in cells expressing human transporters, while clearance of endogenous dopamine was measured by fast-scan cyclic voltammetry in mouse striatal slices.