We used reverse-transfected cell microarrays (RTCM) as an unbiase

We used reverse-transfected cell microarrays (RTCM) as an unbiased systems biology approach to systematically analyze the effects of HHV-8 genes on the NF-kappa B signaling

pathway. All HHV-8 genes individually (n = 86) and, additionally, all K and latent genes in pairwise combinations (n = 231) were investigated. Statistical analyses of more than 14,000 transfections identified ORF75 as a novel and confirmed K13 as a known HHV-8 activator of NF-kappa B. K13 and ORF75 showed cooperative NF-kappa B activation. Small interfering RNA-mediated knockdown of ORF75 expression demonstrated that this gene contributes significantly to NF-kappa B activation in HHV-8-infected Selleckchem SB431542 cells. Furthermore, our approach confirmed K10.5 as an NF-kappa B inhibitor and newly identified K1 as

an inhibitor of both K13- and ORF75-mediated NF-kappa B activation. All results obtained with RTCM were confirmed with classical transfection experiments. Our work describes the first successful application of RTCM for the systematic analysis of pathofunctions of genes of an infectious agent. With this approach, ORF75 and K1 were identified as novel HHV-8 regulatory molecules on the NF-kappa B signal transduction pathway. The genes identified may be involved in fine-tuning of the balance between latency and lytic replication, since this depends critically on the state of NF-kappa B activity.”
“Mechanosensitivity is a crucial but poorly understood property of the sensory nervous system. Transient selleck screening library receptor potential (TRP) channels, MEK162 datasheet which have been found to be responsible for the detection of other sensory stimuli such as temperature and pungent chemicals, have been suggested to also recognize stretch or pressure to cell membranes. TRPC1 is one candidate from studies in oocytes but evidence in native sensory neurons has been lacking. Therefore,

we have measured an increase in intracellular Ca(2+) levels upon mechanical activation of native mouse dorsal root ganglion (DRG) neurons in culture using hypoosmolar buffer. Our results show that down regulation of TRPC1 with short hairpin RNA results in a 65% reduction of neurons with stretch activated responses. These results implicate a direct or indirect involvement of TRPC1 in the mechanosensitivity of DRG neurons. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Human immunodeficiency virus type 1 R5 viruses vary extensively in phenotype. Thus, R5 envelopes (env) in the brain tissue of individuals with neurological complications are frequently highly macrophage-tropic. Macrophage tropism correlates with the capacity of the envelope to exploit low CD4 levels for infection. In addition, the presence of an asparagine at residue 283 within the CD4 binding site has been associated with brain-derived envelopes, increased env-CD4 affinity, and enhanced macrophage tropism.

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