Urokinase Plasminogen Activator Inhibits HIV Virion Release from Macrophage-Differentiated Chronically Infected Cells via Activation of RhoA and PKCε

HIV replication in mononuclear phagocytes is a multi-step process regulated by viral and cellular proteins with the peculiar feature of virion budding and accumulation in intra-cytoplasmic vesicles. Interaction of urokinase-type plasminogen activator (uPA) with its cell surface receptor (uPAR) has been shown to favor virion accumulation in such sub-cellular compartment in primary monocyte-derived macrophages and chronically infected promonocytic U1 cells differentiated into macrophage-like cells by stimulation with phorbol myristate acetate (PMA). By adopting this latter model system, we have here investigated which intracellular signaling pathways were triggered by uPA/uPAR interaction leading the redirection of virion accumulation in intra-cytoplasmic vesicles.uPA induced activation of RhoA, PKCδ and PKCε in PMA-differentiated U1 cells. In the same conditions, RhoA, PKCδ and PKCε modulated uPA-induced cell adhesion and polarization, whereas only RhoA and PKCε were also responsible for the redirection of virions in intracellular vesicles. Distribution of G and F actin revealed that uPA reorganized the cytoskeleton in both adherent and polarized cells. The role of G and F actin isoforms was unveiled by the use of cytochalasin D, a cell-permeable fungal toxin that prevents F actin polymerization. Receptor-independent cytoskeleton remodeling by Cytochalasin D resulted in cell adhesion, polarization and intracellular accumulation of HIV virions similar to the effects gained with uPA.These findings illustrate the potential contribution of the uPA/uPAR system in the generation and/or maintenance of intra-cytoplasmic vesicles that actively accumulate virions, thus sustaining the presence of HIV reservoirs of macrophage origin. In addition, our observations also provide evidences that pathways controlling cytoskeleton remodeling and activation of PKCε bear relevance for the design of new antiviral strategies aimed at interfering with the partitioning of virion budding between intra-cytoplasmic vesicles and plasma membrane in infected human macrophages

Parks, people, and conservation: A review of management issues in nepal's protected areas

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43480/1/11111_2005_Article_BF01254607.pd

Evaluation of Evidence for Altered Behavior and Auditory Deficits in Fishes Due to Human-Generated Noise Sources

In this study, we have evaluated peer-reviewed publications and contracted reports to provide an overview of what is known about auditory processing by fishes and the behavioral and physiological effects of various noise stimuli as documented by the best and most appropriate studies. We include reviews of work on both cartilaginous (sharks, skates, and rays) and teleost fishes (modern bony fishes) and provide recommendations for research to address remaining issues. Clear responses to human-generated noise have been documented in several marine species of interest. Sharks may be attracted to low-frequency pulsed sounds, which can change their normal distributions and could increase agonistic interactions between individuals and/or species. However, sharks also learn to ignore sounds that are not associated with food, so that any change in distribution or local density should return to normal levels eventually. There are no studies that show long-term avoidance of an ensonified area, even though a shark may exhibit a startle response at the onset of a sudden loud noise. Teleost fishes also have specific behavioral responses to some human-generated noise, in particular to seismic surveys and ship noise. The responses range from brief interruptions i