1,859 research outputs found

    Cosmic Histories of Stars, Gas, Heavy Elements, and Dust

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    We present a set of coupled equations that relate the stellar, gaseous, chemical, and radiation constituents of the universe averaged over the whole galaxy population. Using as input the available data from quasar absorption-line surveys, optical imaging and redshift surveys, and the COBE DIRBE and FIRAS extragalactic infrared background measurements, we obtain solutions for the cosmic histories of stars, interstellar gas, heavy elements, dust, and radiation from stars and dust in galaxies. Our solutions reproduce remarkably well a wide variety of observations that were not used as input, including the integrated background light from galaxy counts, the optical and near-infrared emissivities from galaxy surveys, the local infrared emissivities from the IRAS survey, the mean abundance of heavy elements from surveys of damped Lyman-alpha systems, and the global star formation rates from Hα\alpha surveys and submillimeter observations. The solutions presented here suggest that the process of galaxy formation appears to have undergone an early period of substantial inflow to assemble interstellar gas at z3z\gtrsim3, a subsequent period of intense star formation and chemical enrichment at 1z31\lesssim z\lesssim3, and a recent period of rapid decline in the gas content, star formation rate, optical stellar emissivity, and infrared dust emission at z1z\lesssim1. [abridged version]Comment: 29 pages, ApJ in press, 10 Sept 9

    Valence Quark Spin Distribution Functions

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    The hyperfine interactions of the constituent quark model provide a natural explanation for many nucleon properties, including the Delta-N splitting, the charge radius of the neutron, and the observation that the proton's quark distribution function ratio d(x)/u(x)->0 as x->1. The hyperfine-perturbed quark model also makes predictions for the nucleon spin-dependent distribution functions. Precision measurements of the resulting asymmetries A_1^p(x) and A_1^n(x) in the valence region can test this model and thereby the hypothesis that the valence quark spin distributions are "normal".Comment: 16 pages, 2 Postscript figure

    MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens

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    We propose the Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK) method for prioritizing single-guide RNAs, genes and pathways in genome-scale CRISPR/Cas9 knockout screens. MAGeCK demonstrates better performance compared with existing methods, identifies both positively and negatively selected genes simultaneously, and reports robust results across different experimental conditions. Using public datasets, MAGeCK identified novel essential genes and pathways, including EGFR in vemurafenib-treated A375 cells harboring a BRAF mutation. MAGeCK also detected cell type-specific essential genes, including BCR and ABL1, in KBM7 cells bearing a BCR-ABL fusion, and IGF1R in HL-60 cells, which depends on the insulin signaling pathway for proliferation. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0554-4) contains supplementary material, which is available to authorized users

    Orbitally forced ice sheet fluctuations during the Marinoan Snowball Earth glaciation

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    Two global glaciations occurred during the Neoproterozoic. Snowball Earth theory posits that these were terminated after millions of years of frigidity when initial warming from rising atmospheric CO2 concentrations was amplified by the reduction of ice cover and hence a reduction in planetary albedo. This scenario implies that most of the geological record of ice cover was deposited in a brief period of melt-back. However, deposits in low palaeo-latitudes show evidence of glacial–interglacial cycles. Here we analyse the sedimentology and oxygen and sulphur isotopic signatures of Marinoan Snowball glaciation deposits from Svalbard, in the Norwegian High Arctic. The deposits preserve a record of oscillations in glacier extent and hydrologic conditions under uniformly high atmospheric CO2 concentrations. We use simulations from a coupled three-dimensional ice sheet and atmospheric general circulation model to show that such oscillations can be explained by orbital forcing in the late stages of a Snowball glaciation. The simulations suggest that while atmospheric CO2 concentrations were rising, but not yet at the threshold required for complete melt-back, the ice sheets would have been sensitive to orbital forcing. We conclude that a similar dynamic can potentially explain the complex successions observed at other localities

    Chronic Arsenic Exposure and Oxidative Stress: OGG1 Expression and Arsenic Exposure, Nail Selenium, and Skin Hyperkeratosis in Inner Mongolia

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    Arsenic, a human carcinogen, is known to induce oxidative damage to DNA. In this study we investigated oxidative stress and As exposure by determining gene expression of OGG1, which codes for an enzyme, 8-oxoguanine DNA glycosylase, involved in removing 8-oxoguanine in As-exposed individuals. Bayingnormen (Ba Men) residents in Inner Mongolia are chronically exposed to As via drinking water. Water, toenail, and blood samples were collected from 299 Ba Men residents exposed to 0.34–826 μg/L As. RNA was isolated from blood, and mRNA levels of OGG1 were determined using real-time polymerase chain reaction. OGG1 expression levels were linked to As concentrations in drinking water and nails, selenium concentrations in nails, and skin hyperkeratosis. OGG1 expression was strongly associated with water As concentrations (p < 0.0001). Addition of the quadratic term significantly improved the fit compared with the linear model (p = 0.05). The maximal OGG1 response was at the water As concentration of 149 μg/L. OGG1 expression was also significantly associated with toenail As concentrations (p = 0.015) but inversely associated with nail Se concentrations (p = 0.0095). We found no significant differences in the As-induced OGG1 expression due to sex, smoking, or age even though the oldest group showed the strongest OGG1 response (p = 0.0001). OGG1 expression showed a dose-dependent increased risk of skin hyperkeratosis in males (trend analysis, p = 0.02), but the trend was not statistically significant in females. The results from this study provide a linkage between oxidative stress and As exposure in humans. OGG1 expression may be useful as a biomarker for assessing oxidative stress from As exposure

    Lentiviral Vpx Accessory Factor Targets VprBP/DCAF1 Substrate Adaptor for Cullin 4 E3 Ubiquitin Ligase to Enable Macrophage Infection

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    Vpx is a small virion-associated adaptor protein encoded by viruses of the HIV-2/SIVsm lineage of primate lentiviruses that enables these viruses to transduce monocyte-derived cells. This probably reflects the ability of Vpx to overcome an as yet uncharacterized block to an early event in the virus life cycle in these cells, but the underlying mechanism has remained elusive. Using biochemical and proteomic approaches, we have found that Vpx protein of the pathogenic SIVmac 239 strain associates with a ternary protein complex comprising DDB1 and VprBP subunits of Cullin 4–based E3 ubiquitin ligase, and DDA1, which has been implicated in the regulation of E3 catalytic activity, and that Vpx participates in the Cullin 4 E3 complex comprising VprBP. We further demonstrate that the ability of SIVmac as well as HIV-2 Vpx to interact with VprBP and its associated Cullin 4 complex is required for efficient reverse transcription of SIVmac RNA genome in primary macrophages. Strikingly, macrophages in which VprBP levels are depleted by RNA interference resist SIVmac infection. Thus, our observations reveal that Vpx interacts with both catalytic and regulatory components of the ubiquitin proteasome system and demonstrate that these interactions are critical for Vpx ability to enable efficient SIVmac replication in primary macrophages. Furthermore, they identify VprBP/DCAF1 substrate receptor for Cullin 4 E3 ubiquitin ligase and its associated protein complex as immediate downstream effector of Vpx for this function. Together, our findings suggest a model in which Vpx usurps VprBP-associated Cullin 4 ubiquitin ligase to enable efficient reverse transcription and thereby overcome a block to lentivirus replication in monocyte-derived cells, and thus provide novel insights into the underlying molecular mechanism

    Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences

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    Background: Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos. Methods: Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine. Principal Findings: Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype. Conclusions/Significance: Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood
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