1,632 research outputs found

    Disruption of Histone Modification and CARM1 Recruitment by Arsenic Represses Transcription at Glucocorticoid Receptor-Regulated Promoters

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    Chronic exposure to inorganic arsenic (iAs) found in the environment is one of the most significant and widespread environmental health risks in the U.S. and throughout the world. It is associated with a broad range of health effects from cancer to diabetes as well as reproductive and developmental anomalies. This diversity of diseases can also result from disruption of metabolic and other cellular processes regulated by steroid hormone receptors via aberrant transcriptional regulation. Significantly, exposure to iAs inhibits steroid hormone-mediated gene activation. iAs exposure is associated with disease, but is also used therapeutically to treat specific cancers complicating an understanding of iAs action. Transcriptional activation by steroid hormone receptors is accompanied by changes in histone and non-histone protein post-translational modification (PTM) that result from the enzymatic activity of coactivator and corepressor proteins such as GRIP1 and CARM1. This study addresses how iAs represses steroid receptor-regulated gene transcription. PTMs on histones H3 and H4 at the glucocorticoid receptor (GR)-activated mouse mammary tumor virus (MMTV) promoter were identified by chromatin immunoprecipitation analysis following exposure to steroid hormone 6 iAs. Histone H3K18 and H3R17 amino acid residues had significantly different patterns of PTMs after treatment with iAs. Promoter interaction of the coactivator CARM1 was disrupted, but the interaction of GRIP1, a p160 coactivator through which CARM1 interacts with a promoter, was intact. Over-expression of CARM1 was able to fully restore and GRIP1 partially restored iAs-repressed transcription indicating that these coactivators are functionally associated with iAs-mediated transcriptional repression. Both are essential for robust transcription at steroid hormone regulated genes and both are associated with disease when inappropriately expressed. We postulate that iAs effects on CARM1 and GRIP1 may underlie some of its therapeutic effects and as well be associated with its toxic effects

    A Description of the Development, Capabilities, and Operational Status of the Test SLATE Data Acquisition System at the National Transonic Facility

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    The paper will present a brief background of the previous data acquisition system at the National Transonic Facility (NTF) and the reasoning and goals behind the upgrade to the current Test SLATE (Test Software Laboratory and Automated Testing Environments) data acquisition system. The components, performance characteristics, and layout of the Test SLATE system within the NTF control room will be discussed. The development, testing, and integration of Test SLATE within NTF operations will be detailed. The operational capabilities of the system will be outlined including: test setup, instrumentation calibration, automatic test sequencer setup, data recording, communication between data and facility control systems, real time display monitoring, and data reduction. The current operational status of the Test SLATE system and its performance during recent NTF testing will be highlighted including high-speed, frame-by-frame data acquisition with conditional sampling post-processing applied. The paper concludes with current development work on the system including the capability for real-time conditional sampling during data acquisition and further efficiency enhancements to the wind tunnel testing process

    Viability and Application of Mounting Personal PID VOC Sensors to Small Unmanned Aircraft Systems

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    Using a UAS-mounted sensor to allow for a rapid response to areas that may be difficult to reach or potentially dangerous to human health can increase the situational awareness of first responders of an aircraft crash site through the remote detection, identification, and quantification of airborne hazardous materials. The primary purpose of this research was to evaluate the remote sensing viability and application of integrating existing commercial-off-the-shelf (COTS) sensors with small unmanned aircraft system (UAS) technology to detect potentially hazardous airborne contaminants in emergency leak or spill response situations. By mounting the personal photoionization detector (PID) with volatile organic compound VOC sensor technology on UAS platforms, the needed information may be obtained at an optimum range and resolution without needlessly exposing a human to possible adverse conditions

    Sorption of metals by extracellular polymers from the cyanobacterium Microcystis aeruginosa fo. flos-aquae strain C3-40

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    The sorption of cadmium (II), copper (II), lead (II),manganese (II), and zinc (II) by purified capsularpolysaccharide from the cyanobacterium Microcystis aeruginosafo. flos-aquae strainC3-40 was examined by four methods: equilibriumdialysis, metal removal from solution as detected byvoltammetry, metal accumulation by capsule-containingalginate beads, and calorimetry. The polysaccharide's saturation binding capacities for these metals rangedfrom 1.2 to 4 mmol of metal g-1 of capsule, whichcorresponds to 1 metal equivalent per 2 to 4saccharide subunits of the polymer. Competitionbetween paired metals was tested with simultaneous andsequential additions of metal. Cadmium (II) andlead (II), as well as lead (II) and zinc (II), competedrelatively equally and reciprocally for polymerbinding sites. In contrast, manganese (II) stronglyinhibited the binding of cadmium (II) and lead (II), butitself was not substantially inhibited by either theprior or simultaneous adsorption of cadmium (II) or lead (II).The data are interpreted with respect to overlap ofbinding sites and possibilities of altered polymerconformation or solvation. Calorimetric studies oflead (II) and cadmium (II) association reactions withthe polysaccharide suggest that the enthalpies aresmall and that the reactions may be driven by entropy

    An Initiative to Improve Cultural Competence among GYN/OB Providers

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    Healthcare cultural competence is defined as a process of delivering care by meeting the social, cultural, and linguistic needs of diverse populations, and should be optimized at all organizational levels to reduce racial disparities and poor patient outcomes. The American College of Obstetrics and Gynecology (ACOG) recognizes the importance of cultural competence and states that research should be conducted to identify and combat barriers that impede equitable care. In this prospective, pre- and post-intervention study design, we used the Healthcare Provider Cultural Competence Instrument (HPCCI) to measure five dimensions of cultural competence within the Department of Gynecology and Obstetrics in a large academic medical center. The intervention was a single Grand Rounds educational presentation on cultural diversity. Baseline survey response rate was 64%. Post-intervention survey response rate was 30%. Post-intervention survey results showed that cultural competence increased by statistically significant amounts across all five dimensions. Our results show an effective and feasible method to assess baseline cultural competency in a large interprofessional clinical department. Our results also indicate that a single intervention may have some positive impact on levels of cultural competence for a diverse interprofessional health care team

    Initial Observations of Lunar Impact Melts and Ejecta Flows with the Mini-RF Radar

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    The Mini-RF radar on the Lunar Reconnaissance Orbiter's spacecraft has revealed a great variety of crater ejecta flow and impact melt deposits, some of which were not observed in prior radar imaging. The craters Tycho and Glushko have long melt flows that exhibit variations in radar backscatter and circular polarization ratio along the flow. Comparison with optical imaging reveals that these changes are caused by features commonly seen in terrestrial lava flows, such as rafted plates, pressure ridges, and ponding. Small (less than 20 km) sized craters also show a large variety of features, including melt flows and ponds. Two craters have flow features that may be ejecta flows caused by entrained debris flowing across the surface rather than by melted rock. The circular polarization ratios (CPRs) of the impact melt flows are typically very high; even ponded areas have CPR values between 0.7-1.0. This high CPR suggests that deposits that appear smooth in optical imagery may be rough at centimeter- and decimeter- scales. In some places, ponds and flows are visible with no easily discernable source crater. These melt deposits may have come from oblique impacts that are capable of ejecting melted material farther downrange. They may also be associated with older, nearby craters that no longer have a radar-bright proximal ejecta blanket. The observed morphology of the lunar crater flows has implications for similar features observed on Venus. In particular, changes in backscatter along many of the ejecta flows are probably caused by features typical of lava flows

    Mitotic stress is an integral part of the oncogene-induced senescence program that promotes multinucleation and cell cycle arrest

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    Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signaling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here, we show that multinucleate OIS cells originate mostly from failed mitosis. Prior to senescence, mutant H-RasV12 activation in primary human fibroblasts compromised mitosis, concordant with abnormal expression of mitotic genes functionally linked to the observed mitotic spindle and chromatin defects. Simultaneously, H-RasV12 activation enhanced survival of cells with damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional upregulation of Mcl1 was, at least in part, responsible for enhanced survival and slippage of cells with mitotic defects. Importantly, mitotic slippage and oncogene signaling cooperatively induced senescence and key senescence effectors p21 and p16. In summary, activated Ras coordinately triggers mitotic disruption and enhanced cell survival to promote formation of multinucleate senescent cells
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