Sequence similarity between the erythrocyte binding domain 1 of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals binding residues for the Duffy Antigen Receptor for Chemokines

<p>Abstract</p> <p>Background</p> <p>The surface glycoprotein (SU, gp120) of the human immunodeficiency virus (HIV) must bind to a chemokine receptor, CCR5 or CXCR4, to invade CD4+ cells. <it>Plasmodium vivax </it>uses the Duffy Binding Protein (DBP) to bind the Duffy Antigen Receptor for Chemokines (DARC) and invade reticulocytes.</p> <p>Results</p> <p>Variable loop 3 (V3) of HIV-1 SU and domain 1 of the <it>Plasmodium vivax </it>DBP share a sequence similarity. The site of amino acid sequence similarity was necessary, but not sufficient, for DARC binding and contained a consensus heparin binding site essential for DARC binding. Both HIV-1 and <it>P. vivax </it>can be blocked from binding to their chemokine receptors by the chemokine, RANTES and its analog AOP-RANTES. Site directed mutagenesis of the heparin binding motif in members of the DBP family, the <it>P. knowlesi </it>alpha, beta and gamma proteins abrogated their binding to erythrocytes. Positively charged residues within domain 1 are required for binding of <it>P. vivax </it>and <it>P. knowlesi </it>erythrocyte binding proteins.</p> <p>Conclusion</p> <p>A heparin binding site motif in members of the DBP family may form part of a conserved erythrocyte receptor binding pocket.</p

Sequence similarity between the erythrocyte binding domain of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals a functional heparin binding motif involved in binding to the Duffy antigen receptor for chemokines

<p>Abstract</p> <p>Background</p> <p>The HIV surface glycoprotein gp120 (SU, gp120) and the <it>Plasmodium vivax </it>Duffy binding protein (PvDBP) bind to chemokine receptors during infection and have a site of amino acid sequence similarity in their binding domains that often includes a heparin binding motif (HBM). Infection by either pathogen has been found to be inhibited by polyanions.</p> <p>Results</p> <p>Specific polyanions that inhibit HIV infection and bind to the V3 loop of X4 strains also inhibited DBP-mediated infection of erythrocytes and DBP binding to the Duffy Antigen Receptor for Chemokines (DARC). A peptide including the HBM of PvDBP had similar affinity for heparin as RANTES and V3 loop peptides, and could be specifically inhibited from heparin binding by the same polyanions that inhibit DBP binding to DARC. However, some V3 peptides can competitively inhibit RANTES binding to heparin, but not the PvDBP HBM peptide. Three other members of the DBP family have an HBM sequence that is necessary for erythrocyte binding, however only the protein which binds to DARC, the <it>P. knowlesi </it>alpha protein, is inhibited by heparin from binding to erythrocytes. Heparitinase digestion does not affect the binding of DBP to erythrocytes.</p> <p>Conclusion</p> <p>The HBMs of DBPs that bind to DARC have similar heparin binding affinities as some V3 loop peptides and chemokines, are responsible for specific sulfated polysaccharide inhibition of parasite binding and invasion of red blood cells, and are more likely to bind to negative charges on the receptor than cell surface glycosaminoglycans.</p

ESTIMATING RETURNS FROM PAST INVESTMENTS INTO BEEF CATTLE GENETICS RD&E IN AUSTRALIA

This study aimed at estimating the costs and benefits of all beef cattle genetic improvement activity, across Australia, over the period 1970 to the present. The total cumulative Present Value (PV) of investments by industry, government and other agencies into selection, crossbreeding and grading up since 1963, and of imported genetics, was estimated to be $340m (in$2001 at a 7% discount rate). Using a suite of genetic evaluation models, farming systems models and an industry-level model, the cumulative PV of industry returns were estimated. Within-breed selection generated $944m; crossbreeding in southern Australia$255m; changing breed composition in southern Australia $62m; and changing breed composition in northern Australia$8.1bn. The benefit/cost ratio for this investment was 28:1 over the last 30 years.Livestock Production/Industries, Research and Development/Tech Change/Emerging Technologies,

Estimating the Returns from Past Investment into Beef Cattle Genetic Technologies in Australia

Research and Development/Tech Change/Emerging Technologies,

Statistical Computations with AstroGrid and the Grid

We outline our first steps towards marrying two new and emerging technologies; the Virtual Observatory (e.g, AstroGrid) and the computational grid. We discuss the construction of VOTechBroker, which is a modular software tool designed to abstract the tasks of submission and management of a large number of computational jobs to a distributed computer system. The broker will also interact with the AstroGrid workflow and MySpace environments. We present our planned usage of the VOTechBroker in computing a huge number of n-point correlation functions from the SDSS, as well as fitting over a million CMBfast models to the WMAP data.Comment: Invited talk to appear in "Proceedings of PHYSTAT05: Statistical Problems in Particle Physics, Astrophysics and Cosmology

Why do doctored images distort memory?

Doctored images can cause people to believe in and remember experiences that never occurred, yet the underlying mechanism(s) responsible are not well understood. How does compelling false evidence distort autobiographical memory? Subjects were filmed observing and copying a Research Assistant performing simple actions, then they returned 2 days later for a memory test. Before taking the test, subjects viewed video-clips of simple actions, including actions that they neither observed nor performed earlier. We varied the format of the video-clips between-subjects to tap into the source-monitoring mechanisms responsible for the ‘doctored-evidence effect.’ The distribution of belief and memory distortions across conditions suggests that at least two mechanisms are involved: doctored images create an illusion of familiarity, and also enhance the perceived credibility of false suggestions. These findings offer insight into how external evidence influences source-monitoring

Down-regulation of cell surface CXCR4 by HIV-1

<p>Abstract</p> <p>Background</p> <p>CXC chemokine receptor 4 (CXCR4), a member of the G-protein-coupled chemokine receptor family, can serve as a co-receptor along with CD4 for entry into the cell of T-cell tropic X4 human immunodeficiency virus type 1 (HIV-1) strains. Productive infection of T-lymphoblastoid cells by X4 HIV-1 markedly reduces cell-surface expression of CD4, but whether or not the co-receptor CXCR4 is down-regulated has not been conclusively determined.</p> <p>Results</p> <p>Infection of human T-lymphoblastoid cell line RH9 with HIV-1 resulted in down-regulation of cell surface CXCR4 expression. Down-regulation of surface CXCR4 correlated temporally with the increase in HIV-1 protein expression. CXCR4 was concentrated in intracellular compartments in H9 cells after HIV-1 infection. Immunofluorescence microscopy studies showed that CXCR4 and HIV-1 glycoproteins were co-localized in HIV infected cells. Inducible expression of HIV-1 envelope glycoproteins also resulted in down-regulation of CXCR4 from the cell surface.</p> <p>Conclusion</p> <p>These results indicated that cell surface CXCR4 was reduced in HIV-1 infected cells, whereas expression of another membrane antigen, CD3, was unaffected. CXCR4 down-regulation may be due to intracellular sequestering of HIV glycoprotein/CXCR4 complexes.</p

Gut inflammation provides a respiratory electron acceptor for Salmonella.

Salmonella enterica serotype Typhimurium (S. Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S. Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen

On the (non)persuasive power of a brain image

Abstract The persuasive power of brain images has captivated scholars in many disciplines. Like others, we too were intrigued by the finding that a brain image makes accompanying information more credible (McCabe &amp; Castel in Cognition 107:343-352, 2008). But when our attempts to build on this effect failed, we instead ran a series of systematic replications of the original study-comprising 10 experiments and nearly 2,000 subjects. When we combined the original data with ours in a meta-analysis, we arrived at a more precise estimate of the effect, determining that a brain image exerted little to no influence. The persistent meme of the influential brain image should be viewed with a critical eye