BACKGROUND The negative factor (Nef) of human and simian immunodeficiency viruses (HIV-1, HIV-2 and SIV) is required for high levels of viremia and progression to AIDS. Additionally, Nef leads to cellular activation, increased viral infectivity and decreased expression of CD4 on the cell surface. Previously, we and others demonstrated that Nef associates with a cellular serine kinase (NAK) acti...

Previous genetic studies of intersegmental nerve b development have identified several cell-surface proteins required for correct axon guidance to appropriate target muscles. Here we provide evidence that the small GTPase Drac1 also plays a key role in this guidance process. Neuronal expression of the dominant negative mutation Drac1(N17) causes axons to bypass and extend beyond normal synaptic...

Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder that can be characterized by the presence of protein inclusions containing mutant huntingtin within a subset of neurons in the brain. Since their discovery, the relevance of inclusions to disease pathology has been controversial. We show using super-resolution fluorescence imaging and Förster resonance energy transfe...

The branching ratios of the measured decay KL → ππee and of the still unmeasured decay K → ππee are calculated to next-to-leading order in Chiral Perturbation Theory (CHPT). Recent experimental results are used to determine two possible values of the combination (N r 16 −N17) of weak lowenergy couplings (LECs) from the O(p4) chiral Lagrangian. The obtained values are compared to the predictions...

Interfering with cellular signal transduction pathways is a common strategy used by many viruses to create a propitious intracellular environment for an efficient replication. Our group has been studying cellular signalling pathways activated by the orthopoxviruses Vaccinia (VACV) and Cowpox (CPXV) and their significance to viral replication. In the present study our aim was to investigate whet...

The genome of Salmonella enterica subsp. enterica serotype Senftenberg N17-509, a strain isolated from desiccated coconut, was sequenced using single-molecule real-time sequencing. It consists of a 5.1-Mbp chromosome and a 29-kb linear plasmid.

The c-Jun N-terminal kinases (JNKs) are activated strongly by inflammatory cytokines and environmental stresses, but only weakly by growth factors. Here we show that platelet-derived growth factor (PDGF) strongly potentiates activation of JNK by interleukin 1 (IL-1) in human fibroblasts and a pig aortic endothelial (PAE) cell line. This synergistic activation of JNK by IL-1 and PDGF was unaffec...

The ability of signaling via the JNK (c-Jun NH2-terminal kinase)/stress-activated protein kinase cascade to stimulate or inhibit DNA synthesis in primary cultures of adult rat hepatocytes was examined. Treatment of hepatocytes with media containing hyperosmotic glucose (75 mM final), tumor necrosis factor alpha (TNFalpha, 1 ng/ml final), and hepatocyte growth factor (HGF, 1 ng/ml final) caused ...

BACKGROUND In insulin-sensitive cells, such as adipocytes and skeletal muscle, the activation of phosphoinositide 3-kinase (PI 3-kinase) is thought to be critical in allowing insulin to stimulate both the uptake of glucose and the translocation of a specialized glucose transporter, GLUT4, to the plasma membrane. However, the downstream mediators that couple PI 3-kinase to GLUT4 translocation ar...