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“The plus-strand RNA genome of Sindbis virus (SINV) encodes four nonstructural proteins (nsP1 to nsP4) that are involved in the replication of the viral RNA. The similar to 800-amino-acid nsP2 consists of an N-terminal domain with nucleoside triphosphatase and helicase activities and a C-terminal protease domain. Recently, the structure determined for Venezuelan equine encephalitis

virus nsP2 indicated the presence of a previously unrecognized methyltransferase (MTase)-like domain within the C-terminal similar to 200 residues and raised a question about its functional importance. To assess the role of this MTase-like region in viral replication, highly conserved arginine and lysine selleck screening library residues were mutated to alanine. The plaque phenotypes of these mutants ranged from large/wild-type to small plaques with selected

mutations demonstrating temperature sensitive lethality. The proteolytic polyprotein processing activity of nsP2 was unaffected in most of the mutants. Some of the temperature-sensitive mutants showed reduction in the minus-strand RNA synthesis, a function that has not yet been ascribed to nsP2. Mutation GSK621 order of SINV residue R615 rendered the virus noncytopathic and incapable of inhibiting the host cell translation but with no effects on the transcriptional inhibition. This property differentiated the mutation at R615 from previously described noncytopathic mutations. These results implicate Megestrol Acetate nsP2 in regulation of minus-strand synthesis and suggest that different regions of the nsP2 MTase-like domain differentially modulate host defense mechanisms, independent of its role as the viral protease.”
“Objective: To test the hypothesis that emotion recognition and apathy share the same functional circuit involving the subthalamic nucleus (STN).

Methods: A consecutive series of 17 patients

with advanced Parkinson’s disease (PD) was assessed 3 months before (M – 3) and 3 months (M + 3) after STN deep brain stimulation (DBS). Mean (+/- S.D.) age at surgery was 56.9 (8.7) years. Mean disease duration at surgery was 11.8 (2.6) years. Apathy was measured using the Apathy Evaluation Scale (AES) at both M-3 and M3. Patients were also assessed using a computerised paradigm of facial emotion recognition [Ekman, R, & Friesen, W. V. (1976). Pictures of facial affect. Palo Alto: Consulting Psychologist Press] before and after STN DBS. Prior to this, the Benton Facial Recognition Test was used to check that the ability to perceive faces was intact.

Results: Apathy had significantly worsened at M3 (42.5 +/- 8.9, p = 0.006) after STN-DBS, in relation to the preoperative assessment (37.2 +/- 5.5). There was also a significant reduction in recognition percentages for facial expressions of fear (43.1% +/- 22.9 vs. 61.6% +/- 21.4, p = 0.022) and sadness (52.7% +/- 19.1 vs. 67.6% +/- 22.8, p = 0.031) after STN DBS.