(C) 2008 Elsevier Ltd. All rights reserved.”
“Nuclear pore complex (NPC) proteins are known for their critical roles in regulating nucleocytoplasmic traffic of macromolecules across the nuclear envelope. However, recent findings suggest that some nucleoporins (Nups), including Nup98, have additional functions in developmental gene regulation. Nup98, which exhibits transcription-dependent mobility at the NPC but can also bind chromatin away from the nuclear envelope, is frequently

involved in chromosomal translocations in a subset of patients suffering from acute myeloid leukemia (AML). A common paradigm suggests that Nup98 translocations cause aberrant transcription when they are recuited to aberrant genomic loci. Importantly, this model fails to account for the potential loss of wild type (WT) Nup98 function in the presence of Nup98 translocation mutants. Here we examine

how the cell might regulate Nup98 nucleoplasmic protein Selleckchem NVP-BSK805 levels to control transcription in healthy cells. In addition, we discuss the possibility that dominant negative Nup98 fusion proteins disrupt the transcriptional activity of WT Nup98 in the nucleoplasm to drive AML.”
“The replication of dengue virus (DENV) RNA requires at least two viral non-structural selleck chemical (NS) proteins, NS3 and NS5. To facilitate the study of the DENV replication complex, human monoclonal IgG that are specific for NS proteins have been generated and characterised. Carteolol HCl The anti-NS3 IgG,3F8, binds a conserved epitope (aa526-531) in the NS3 helicase domain, and cross-reacts with NS3 from all four DENV serotypes and the related yellow fever virus. The anti-NS2B IgG, 3F10, binds aa49-66 of NS2B (CF18), which forms part of the 47 aa hydrophilic cofactor region required for NS3 protease activity. The specificity of the

IgG for their respective non-structural proteins has been demonstrated by immunofluorescence of cells infected with DENV and Western blotting. 3F8 is able to co-immunoprecipitate NS3 and NS5 from BHK-21 cells infected with DENV2, and 3F10 is able to detect an interaction between recombinant NS2B(CF18)NS3 full-length protein and the NS5 RNA-dependent RNA polymerase (RdRp) domain in an ELISA-based binding assay. The assay is specific and highly reproducible, with a clear binding curve seen when RdRp is incubated with increasing amounts of full-length NS3, but not the NS3 protease domain. The NS3 helicase domain competes with NS3 full-length for NS5 RdRp binding, with a K-d of 2.5 mu M. Since NS3 and NS5 are required for DENV replication, this fascile assay could be used to screen for non-nucleoside, allosteric inhibitors that disrupt the interaction between the two proteins. (C) 2011 Elsevier B.V. All rights reserved.”
“A profound rise in secretary activity in the early morning hours hallmarks the circadian regulation of the hypothalamic-pituitary adrenal (HPA) stress axis.