Site-directed mutagenesis identified two highly conserved arginines, R379 and R389, on the N-terminal side of the V3 stem as critical for the contact between SU and HSPG. Residues K407, K409, K410, and K412 on the C-terminal side of the V3 stem form a second nonconserved domain necessary for HSPG binding, consistent with the observed specificity distinctions with FS FIV. Our findings discriminate structural determinants important for HSPG and CXCR4 binding by FIV SU and thus further define the importance of the V3 loop for virus entry and infection.”
“Edaravone is a novel free radical scavenger

that is clinically employed in patients with acute cerebral infarction. ABT737 However, its effect on stroke-induced subventricular zone (SVZ) neurogenesis is largely unknown. In this study, we investigated the effect and underlying mechanism of edaravone administration on SVZ neurogenesis using a rat model of cerebral ischemia-reperfusion injury. Male Sprague-Dawley rats (200-250 g) were divided into sham operated (n=15), control (n=50), and edaravone-treated (n=50) groups. Rats in the control and edaravone-treated groups underwent 90 min of middle cerebral artery occlusion (MCAO) following reperfusion. Immediately and 12 h after MCAO, the rats received either normal saline (control group) or edaravone (edaravone-treated group) intraperitoneally. 5-bromo-2-deoxyuridine

(BrdU) was used to label proliferating cells. Six, 12, and 24 hours after ischemia, reactive oxygen species (ROS) generation, hypoxia-inducible factor 1 Selleckchem GSK461364 alpha (HIF-1 alpha), and vascular endothelial growth factor (VEGF) protein levels in ischemic ipsilateral SVZ were determined. Immunohistochemistry staining for BrdU and doublecortin (DCX) was performed at 1, 4, and 7 days after ischemia. Treatment with edaravone not only mitigated cerebral infarct size (P<0.05) and neurological defects (P<0.05), but also decreased cell proliferation and neural progenitor cells in the the ischemic ipsilateral SVZ (P<0.05).

Additionally, edaravone reduced effectively ROS generation and HIF-1 alpha as well as VEGF protein levels in the ischemic ipsilateral SVZ (P<0.05). These findings indicate that administration with edaravone, via repressing HIF-1 alpha signaling pathway, inhibits SVZ neurogenesis in rats after cerebral ischemia-reperfusion injury. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Background and purpose The effects of sleep deprivation are a burden in our 24-h society. The use of wake-promoting compounds could improve the performance in situations where sleep cannot be allowed. In this study, the efficacy of the wake-promoting compounds, modafinil and caffeine, in counteracting the effects of 24-h sleep deprivation in the marmoset monkey were tested. As caffeine is habitually used, the efficacy of both compounds after short- and long-term use was investigated.