0 mg/kg, i.p.). In the black and white model, genistein (0.5 y 1.0 mg/kg) and diazepam reduced the latency to enter and increased the time spent into the white compartment; also, significantly increased frequency AZD1208 in vivo and time spent in exploration toward white compartment was seen, as compared with the control group (p < 0.05). In the open field test, genistein and diazepam increased grooming and rearing, without significant changes in locomotor activity, as compared with the control group. In conclusion, phytoestrogen

genistein produces an anxiolytic-like effect in Wistar rats with long-term absence of ovarian hormones in the black and white model, supporting the hypotheses that phytoestrogens could be used to ameliorate

anxiety associated with menopause. (c) 2009 Elsevier Inc. All rights reserved.”
“Human cytomegalovirus infections involve the extensive modification of host cell pathways, including cell cycle control, the regulation of the DNA damage response, and averting promyelocytic FRAX597 order leukemia (PML)-mediated antiviral responses. The UL35 gene from human cytomegalovirus is important for viral gene expression and efficient replication and encodes two proteins, UL35 and UL35a, whose mechanism of action is not well understood. Here, affinity purification coupled with mass spectrometry was used to identify previously unknown human cellular targets of UL35 and UL35a. We demonstrate that both viral proteins interact with the ubiquitin-specific protease USP7, and that UL35 expression can alter USP7 subcellular localization. In addition, UL35 (but not UL35a) was found to associate see more with three components of the Cul4(DCAF1) E3 ubiquitin ligase complex (DCAF1, DDB1, and DDA1) previously shown to be targeted by the HIV-1 Vpr protein. The coimmunoprecipitation and immunofluorescence microscopy of DCAF1 mutants revealed that the C-terminal region of DCAF1 is required for association with UL35 and mediates the dramatic relocalization

of DCAF1 to UL35 nuclear bodies, which also contain conjugated ubiquitin. As previously reported for the Vpr-DCAF1 interaction, UL35 (but not UL35a) expression resulted in the accumulation of cells in the G(2) phase of the cell cycle, which is typical of a DNA damage response, and activated the G(2) checkpoint in a DCAF1-dependent manner. In addition, UL35 (but not UL35a) induced gamma-H2AX and 53BP1 foci, indicating the activation of DNA damage and repair responses. Therefore, the identified interactions suggest that UL35 can contribute to viral replication through the manipulation of host responses.”
“BACKGROUND

Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis.