In addition to having its effect on transcription, Tat has been shown to be involved in splicing. In this study, we demonstrate that Tat interacts with

cyclin-dependent kinase 13 (CDK13) both in AZD3965 clinical trial vivo and in vitro. We also found that CDK13 increases HIV-1 mRNA splicing and favors the production of the doubly spliced protein Nef. In addition, we demonstrate that CDK13 acts as a possible restriction factor, in that its overexpression decreases the production of the viral proteins Gag and Env and subsequently suppresses virus production. Using small interfering RNA against CDK13, we show that silencing of CDK13 leads to a significant increase in virus production. Finally, we demonstrate that CDK13 mediates its effect on splicing through the phosphorylation of ASF/SF2.”
“The present study investigates the effects of divalent and trivalent

manganese (Mn(2+)/Mn(3+)) mixture inhalation on mice to obtain a novel animal model of Parkinson disease (PD) inducing bilateral and progressive cell death in the substantia nigra compacta (SNc) and correlating these alterations with motor disturbances. CD-1 male mice inhaled a mixture of 0.04 M manganese chloride (MnCl(2)) and manganese acetate (Mn(OAc)(3)), 1 h twice a week for 5 months. Before Mn exposure, animals were trained Tubastatin A manufacturer to perform motor function tests and were evaluated each week after the exposure. By doing this, overall behavior was assessed by ratings and by videotaped analyses; by the end of Mn HAS1 exposure period, animals were killed. The mesencephalon was processed for tyrosine hydroxylase (TH) immunocytochemistry. After 5 months of Mn mixture inhalation,

mice developed evident deficits in their motor performance manifested as akinesia, postural instability and action tremor. SNc of the Mn-exposed animals showed an important decrease (67.58%) in the number of TH-immunopositive neurons. Our data provide evidence that MnCl(2) and Mn(OAc)(3) mixture inhalation produces similar morphological and behavioral alterations to those observed in PD providing a useful experimental model for the study of this neurodegenerative disease. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“In contrast to Old World monkeys, most New World monkeys (NWMs) are not susceptible to poliovirus (PV), regardless of the route of infection. We have investigated the molecular basis of restricted PV pathogenesis of NWMs with two kidney cell lines of NWMs, TMX (tamarin) and NZP-60 (marmoset), and characterized their PV receptor homologues. TMX cells were susceptible to infection by PV1 (Mahoney) and PV3 (Leon) but not by PV2 (Lansing). Binding studies to TMX cells indicated that the formation of PV/receptor complexes increased when measured first at 4 degrees C and then at 25 degrees C, whereas PV2 did not significantly bind to TMX cells at either temperature.