Here, we sought to identify the cleavage/packaging signals of human cytomegalovirus. Our results show that a previously proposed pac2-like poly(A) tract is dispensable for cleavage/packaging function and suggest that human cytomegalovirus may utilize a cryptic pac2 motif that lacks a poly(A) tract characteristic of pac2 motifs in other herpesviruses. Additional distal sequences 47 to 100 bp from the point of cleavage were found to enhance
cleavage efficiency. These results should facilitate the identification of trans-acting factors that bind to these cis elements and elucidation of their functions. Such information will be critical for understanding the molecular basis of this complex PKC412 process.”
“Thalamic and extrathalamic nicotinic alpha 4 beta 2 receptors found in the brain have been implicated in Alzheimer’s disease, Parkinson’s disease, substance abuse and other disorders. We report here the development of 3-(2-(S)-azetidinylmethoxy)-5-(3′-fluoropropyl)pyridine www.selleckchem.com/products/ml323.html (nifzetidine) as a new putative high-affinity antagonist for nicotinic alpha 4 beta 2 receptors. Nifzetidine in rat brain homogenate assays containing alpha 4 beta 2 sites labeled with H-3-cytisine exhibited a binding affinity: Ki=0.67 nM. The fluorine-18 analog, 3-(2-(5)-azetidinylmethoxy)-5-(3′-F-18-fluoropropyl)pyridine (F-18-nifzetidine), was synthesized in 20%-40% yield, and apparent specific activity was estimated to be above 2 Ci/mu mol. Rat brain slices
indicated selective binding of F-18-nifzetidine to thalamus, subiculum, striata, cortex and other regions consistent with alpha 4 beta 2 receptor distribution. This selective binding buy GDC-0973 was displaced >85% by 150 mu M nicotine. Positron emission tomography (PET) imaging studies of F-18-nifzetidine in anesthetized rhesus
monkey showed slow uptake in the various brain regions. Retention of (1)8(F)-nifzetidine was maximal in the thalamus and lateral geniculate followed by regions of the temporal and frontal cortex. Cerebellum showed the least uptake. Thalamus to cerebellum ratio was about 2.3 at 180 min postinjection and continued to rise. F-18-Nifzetidine shows promise as a new PET imaging agent for alpha 4 beta 2 nAChR. However, the slow kinetics suggests a need for >3-h PET scans for quantitative studies of the alpha 4 beta 2 nAChRs. (C) 2011 Elsevier Inc. All rights reserved.”
“Nodaviruses are small nonenveloped spherical viruses with a bipartite genome of RNAs. In nodaviruses, subgenomic RNA3 (sgRNA3) plays a critical role in viral replication and survival, as it coordinates the replication of two viral genomic RNAs (RNA1 and RNA2) and encodes protein B2, which is a potent RNA-silencing inhibitor. Despite its importance, the molecular mechanism of nodaviral sgRNA3 synthesis is still poorly understood. Here, we propose that sgRNA3 of Wuhan nodavirus (WhNV) is internally initiated from a promoter on the negative template of genomic RNA1.