69 research outputs found

    Analysis of the Macaca mulatta transcriptome and the sequence divergence between Macaca and human

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    We report the initial sequencing and comparative analysis of the Macaca mulatta transcriptome. Cloned sequences from 11 tissues, nine animals, and three species (M. mulatta, M. fascicularis, and M. nemestrina) were sampled, resulting in the generation of 48,642 sequence reads. These data represent an initial sampling of the putative rhesus orthologs for 6,216 human genes. Mean nucleotide diversity within M. mulatta and sequence divergence among M. fascicularis, M. nemestrina, and M. mulatta are also reported

    Adaptations in a hierarchical food web of southeastern Lake Michigan

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    Two issues in ecological network theory are: (1) how to construct an ecological network model and (2) how do entire networks (as opposed to individual species) adapt to changing conditions? We present a novel method for constructing an ecological network model for the food web of southeastern Lake Michigan (USA) and we identify changes in key system properties that are large relative to their uncertainty as this ecological network adapts fromone time point to a second time point in response to multiple perturbations. To construct our foodweb for southeastern Lake Michigan,we followed the list of seven recommendations outlined in Cohen et al. [Cohen, J.E., et al., 1993.Improving foodwebs. Ecology 74, 252–258] for improving food webs. We explored two inter-related extensions of hierarchical system theory with our food web; the first one was that subsystems react to perturbations independently in the short-term and the second onewas that a system’s properties change at a slower rate than its subsystems’ properties. We used Shannon’s equations to provide quantitative versions of the basic food web properties: number of prey, number of predators, number of feeding links, and connectance (or density).We then compared these properties between the two time-periods by developing distributions of each property for each time period that took uncertainty about the property into account.We compared these distributions, and concluded that non-overlapping distributions indicated changes in these properties that were large relative to their uncertainty. Two subsystems were identified within our food web system structure (p \u3c 0.001). One subsystem had more non-overlapping distributions in food web properties between Time 1 and Time 2 than the other subsystem. The overall system had all overlapping distributions in food web properties between Time 1 and Time 2. These results supported both extensions of hierarchical systems theory. Interestingly, the subsystemwithmore non-overlapping distributions in foodweb propertieswas the subsystemthat contained primarily benthic taxa, contrary to expectations that the identifiedmajor perturbations (lower phosphorous inputs and invasive species) would more greatly affect the subsystem containing primarily pelagic taxa. Future food-web research shouldemploy rigorous statistical analysis and incorporate uncertainty in food web properties for a better understanding of how ecological networks adapt

    The Interferon Response Inhibits HIV Particle Production by Induction of TRIM22

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    Treatment of human cells with Type 1 interferons restricts HIV replication. Here we report that the tripartite motif protein TRIM22 is a key mediator. We used transcriptional profiling to identify cellular genes that were induced by interferon treatment and identified TRIM22 as one of the most strongly up-regulated genes. We confirmed, as in previous studies, that TRIM22 over-expression inhibited HIV replication. To assess the role of TRIM22 expressed under natural inducing conditions, we compared the effects of interferon in cells depleted for TRIM22 using RNAi and found that HIV particle release was significantly increased in the knockdown, implying that TRIM22 acts as a natural antiviral effector. Further studies showed that TRIM22 inhibited budding of virus-like particles containing Gag only, indicating that Gag was the target of TRIM22. TRIM22 did not block the release of MLV or EIAV Gag particles. Inhibition was associated with diffuse cytoplasmic staining of HIV Gag rather than accumulation at the plasma membrane, suggesting TRIM22 disrupts proper trafficking. Mutational analyses of TRIM22 showed that the catalytic amino acids Cys15 and Cys18 of the RING domain are required for TRIM22 antiviral activity. These data disclose a pathway by which Type 1 interferons obstruct HIV replication

    Can Non-lytic CD8+T Cells Drive HIV-1 Escape?

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    The CD8+ T cell effector mechanisms that mediate control of HIV-1 and SIV infections remain poorly understood. Recent work suggests that the mechanism may be primarily non-lytic. This is in apparent conflict with the observation that SIV and HIV-1 variants that escape CD8+ T cell surveillance are frequently selected. Whilst it is clear that a variant that has escaped a lytic response can have a fitness advantage compared to the wild-type, it is less obvious that this holds in the face of non-lytic control where both wild-type and variant infected cells would be affected by soluble factors. In particular, the high motility of T cells in lymphoid tissue would be expected to rapidly destroy local effects making selection of escape variants by non-lytic responses unlikely. The observation of frequent HIV-1 and SIV escape poses a number of questions. Most importantly, is the consistent observation of viral escape proof that HIV-1- and SIV-specific CD8+ T cells lyse infected cells or can this also be the result of non-lytic control? Additionally, the rate at which a variant strain escapes a lytic CD8+ T cell response is related to the strength of the response. Is the same relationship true for a non-lytic response? Finally, the potential anti-viral control mediated by non-lytic mechanisms compared to lytic mechanisms is unknown. These questions cannot be addressed with current experimental techniques nor with the standard mathematical models. Instead we have developed a 3D cellular automaton model of HIV-1 which captures spatial and temporal dynamics. The model reproduces in vivo HIV-1 dynamics at the cellular and population level. Using this model we demonstrate that non-lytic effector mechanisms can select for escape variants but that outgrowth of the variant is slower and less frequent than from a lytic response so that non-lytic responses can potentially offer more durable control

    Measurement of D+- and D0 production in deep inelastic scattering using a lifetime tag at HERA

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    The production of D-+/-- and D-0-mesons has been measured with the ZEUS detector at HERA using an integrated luminosity of 133.6 pb(-1). The measurements cover the kinematic range 5 < Q(2) < 1000 GeV2, 0.02 < y < 0.7, 1.5 < p(T)(D) < 15 GeV and |eta(D)| < 1.6. Combinatorial background to the D-meson signals is reduced by using the ZEUS microvertex detector to reconstruct displaced secondary vertices. Production cross sections are compared with the predictions of next-to-leading-order QCD, which is found to describe the data well. Measurements are extrapolated to the full kinematic phase space in order to obtain the open-charm contribution, F-2(c (c) over bar), to the proton structure function, F-2
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