1,501 research outputs found

    Cell-to-cell transmission and intrinsic mechanisms that influence human immunodeficiency virus infection

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    Early in the course of human immunodeficiency virus (HIV) infection a population of latently infected cells is established which persists despite long-term anti-retroviral treatment. This latent reservoir of HIV-infected cells, which reflects mechanisms of transcriptional repression, is the major barrier to cure. Efforts to target the latent reservoir have been inefficient, indicating a need for a more complete understanding of how HIV transcription is regulated. The molecular networks involved in the regulation of HIV transcription remain incompletely defined. I hypothesized that utilization of a high throughput enhanced yeast one-hybrid assay would reveal novel host transcription factor-long terminal repeat (LTR) interactions and transcriptional networks that regulate HIV. The screen identified 42 human transcription factors and 85 total protein-DNA interactions with HIV LTRs. I investigated a subset of these factors for transcriptional activity in cell-based models of infection. Krüppel-like factors 2 and 3 (KLF2 and KLF3) are repressors of HIV-1 and HIV-2 transcription whereas PLAG1-like zinc finger 1 (PLAGL1) is an activator of HIV-2 transcription. These factors regulate HIV expression through direct protein-DNA interactions and correlate with epigenetic modifications of the HIV LTR. Multiple signals converging from the cellular environment and cell-cell interactions converge at the HIV LTR to determine HIV replication and transcription. Previous work in our lab has shown that strong signaling through the T cell receptor (TCR) was required to support HIV expression and the establishment of an inducible latent infection, whereas weak TCR signaling was insufficient for these outcomes. I hypothesized that dendritic cells-CD4+ T cell interactions provide signals that compensate for weak TCR signaling, supporting HIV-1 expression and generation of inducible latent infection. I used CD4+ T cells that express chimeric antigen receptors in a dendritic cell coculture model to deliver differential signals to CD4+ T cells during cell-to-cell transmission of HIV. I found that signals from dendritic cells compensate for weak TCR signaling, facilitating cell activation, HIV expression and establishment of an inducible infection

    Vascularization predicts overall survival and risk of transformation in follicular lymphoma

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    STP-53912) and by the Fundacao para a Ciencia e Tecnologia (FCT BD13230/2003), Portugal.Follicular lymphoma patients display heterogeneous overall survival and variable risk of transformation. Recent studies have highlighted the role of the microenvironment. The contribution of microvessel density to follicular lymphoma survival remains controversial. We used a quantitative tumor mapping approach to determine whether the degree of vascularization correlated with outcome in a uniformly treated cohort. Whole-tissue sections of diagnostic biopsies from 84 cases were stained for CD34 and tumor-to-vessel-distance that encompassed 90% of the tumor (TVD90) was determined using image analysis. Twenty-one cases with lower TVD90 showed inferior overall survival (P=0.0001) and high risk of transformation (P=0.01). These cases significantly correlated with increased Lymphoma-Associated Macrophages (x(2)=0.025). In multivariate analysis macrophages content, IPI and TVD90 were independent predictors of overall survival (P=0.05, P=0.001 and P=0.01, respectively) and IPI and TVD90 predicted risk of transformation (P=0.008 and P=0.08, respectively). Increased angiogenesis is an independent marker of inferior survival and may promote transformation.publishersversionpublishe

    Dissecting the difference in tree species richness between Africa and South America

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    peer reviewedSignificanceOur full-scale comparison of Africa and South America's lowland tropical tree floras shows that both Africa and South America's moist and dry tree floras are organized similarly: plant families that are rich in tree species on one continent are also rich in tree species on the other continent, and these patterns hold across moist and dry environments. Moreover, we confirm that there is an important difference in tree species richness between the two continents, which is linked to a few families that are exceptionally diverse in South American moist forests, although dry formations also contribute to this difference. Plant families only present on one of the two continents do not contribute substantially to differences in tree species richness

    Evidence for Color Dichotomy in the Primordial Neptunian Trojan Population

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    In the current model of early Solar System evolution, the stable members of the Jovian and Neptunian Trojan populations were captured into resonance from the leftover reservoir of planetesimals during the outward migration of the giant planets. As a result, both Jovian and Neptunian Trojans share a common origin with the primordial disk population, whose other surviving members constitute today's trans-Neptunian object (TNO) populations. The cold classical TNOs are ultra-red, while the dynamically excited "hot" population of TNOs contains a mixture of ultra-red and blue objects. In contrast, Jovian and Neptunian Trojans are observed to be blue. While the absence of ultra-red Jovian Trojans can be readily explained by the sublimation of volatile material from their surfaces due to the high flux of solar radiation at 5AU, the lack of ultra-red Neptunian Trojans presents both a puzzle and a challenge to formation models. In this work we report the discovery by the Dark Energy Survey (DES) of two new dynamically stable L4 Neptunian Trojans,2013 VX30 and 2014 UU240, both with inclinations i >30 degrees, making them the highest-inclination known stable Neptunian Trojans. We have measured the colors of these and three other dynamically stable Neptunian Trojans previously observed by DES, and find that 2013 VX30 is ultra-red, the first such Neptunian Trojan in its class. As such, 2013 VX30 may be a "missing link" between the Trojan and TNO populations. Using a simulation of the DES TNO detection efficiency, we find that there are 162 +/- 73 Trojans with Hr < 10 at the L4 Lagrange point of Neptune. Moreover, the blue-to-red Neptunian Trojan population ratio should be higher than 17:1. Based on this result, we discuss the possible origin of the ultra-red Neptunian Trojan population and its implications for the formation history of Neptunian Trojans

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

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    The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

    The circumpolar impacts of climate change and anthropogenic stressors on Arctic cod (Boreogadus saida) and its ecosystem

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    Arctic cod biomass are predicted. In most Arctic seas, the relative abundance of Arctic cod within the fish community will likely fluctuate in accordance with cold and warm periods. A reduced abundance of Arctic cod will negatively affect the abundance, distribution, and physiological condition of certain predators, whereas some predators will successfully adapt to a more boreal diet. Regional management measures that recognize thecritical roleof Arcticcod arerequiredtoensure that increased anthropogenic activities do not exacerbate the impacts of climate change on Arctic marine ecosystems. Ultimately, the mitigation of habitat loss for Arctic cod will only be achieved through a global reduction in carbon emissions
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