374 research outputs found

    Reward-related attentional capture and cognitive inflexibility interact to determine greater severity of compulsivity-related problems.

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    BACKGROUND AND OBJECTIVES: Neurocognitive processes are key drivers of addictive and compulsive disorders. The current study examined whether reward-related attentional capture and cognitive inflexibility are associated with impulsive and/or compulsive personality traits, and whether these cognitive characteristics interact to predict greater compulsivity-related problems across obsessive-compulsive and drinking behaviors. METHODS: One-hundred and seventy-three participants (mean age = 34.5 years, S.D = 8.4, 42% female) completed an online visual search task to measure reward-related attentional capture and its persistence following reversal of stimulus-reward contingencies. Participants also completed questionnaires to assess trait impulsivity, compulsivity, alcohol use, and obsessive-compulsive behaviors. RESULTS: Greater reward-related attentional capture was associated with trait compulsivity, over and above all impulsivity dimensions, while greater cognitive inflexibility was associated with higher negative urgency (distress-elicited impulsivity). Reward-related attentional capture and cognitive inflexibility interacted to predict greater compulsivity-related problems among participants who reported obsessive-compulsive behaviors in the past month (n = 57) as well as current drinkers (n = 88). Follow-up analyses showed that, for OCD behaviors, this interaction was driven by an association between higher reward-related attentional capture and more problematic behaviors among cognitively inflexible participants only. For drinking, the same pattern was seen, albeit at trend level. LIMITATIONS: This study includes a non-clinical, online sample and is cross-sectional, thus its findings need to be interpreted with these limitations in mind. CONCLUSIONS: Reward-related attentional capture and cognitive flexibility are related to trait compulsivity and impulsivity (negative urgency) respectively, and interact to determine more problematic behaviors

    Interplay between REST and nucleolin transcription factors: a key mechanism in the overexpression of genes upon increased phosphorylation

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    Non-malignant cells can be transformed via the activation of kinases that control degradation of neural-restrictive silencer factor (REST). Here, we identify a mechanism that contributes to the activation of genes, expression of which is controlled by responsive elements containing overlapping binding sites for REST and nucleolin. We demonstrate that both phosphorylated and non-phosphorylated nucleolin-bound DNA; however, only phosphorylated nucleolin successfully competed with either full-length REST or a REST-derived DNA-binding peptide, REST68, for binding to the overlapping binding sites. We show that this interplay between the two transcription factors regulates the activation of cell survival and immunomodulatory genes in tumors and non-malignant cells with activated protein kinase C, which is accompanied with alterations in cell proliferation and apoptosis. We propose a model for the regulation of these genes, which brings a new insight into the molecular mechanisms that control cellular transformation driven by activation of protein kinases

    Evolutionary Diversification of SPANX-N Sperm Protein Gene Structure and Expression

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    The sperm protein associated with nucleus in the X chromosome (SPANX) genes cluster at Xq27 in two subfamilies, SPANX-A/D and SPANX-N. SPANX-A/D is specific for hominoids and is fairly well characterized. The SPANX-N gave rise to SPANX-A/D in the hominoid lineage ∌7 MYA. Given the proposed role of SPANX genes in spermatogenesis, we have extended studies to SPANX-N gene evolution, variation, regulation of expression, and intra-sperm localization. By immunofluorescence analysis, SPANX-N proteins are localized in post-meiotic spermatids exclusively, like SPANX-A/D. But in contrast to SPANX-A/D, SPANX-N are found in all ejaculated spermatozoa rather than only in a subpopulation, are localized in the acrosome rather than in the nuclear envelope, and are expressed at a low level in several nongametogenic adult tissues as well as many cancers. Presence of a binding site for CTCF and its testis-specific paralogue BORIS in the SPANX promoters suggests, by analogy to MAGE-A1 and NY-ESO-1, that their activation in spermatogenesis is mediated by the programmed replacement of CTCF by BORIS. Based on the relative density of CpG, the more extended expression of SPANX-N compared to SPANX-A/D in nongametogenic tissues is likely attributed to differences in promoter methylation. Our findings suggest that the recent duplication of SPANX genes in hominoids was accompanied by different localization of SPANX-N proteins in post-meiotic sperm and additional expression in several nongonadal tissues. This suggests a corresponding functional diversification of SPANX gene families in hominoids. SPANX proteins thus provide unique targets to investigate their roles in the function of spermatozoa, selected malignancies, and for SPANX-N, in other tissues as well

    Strong atmospheric chemistry feedback to climate warming from Arctic methane emissions

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    Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 25 (2011): GB2002, doi:10.1029/2010GB003845.The magnitude and feedbacks of future methane release from the Arctic region are unknown. Despite limited documentation of potential future releases associated with thawing permafrost and degassing methane hydrates, the large potential for future methane releases calls for improved understanding of the interaction of a changing climate with processes in the Arctic and chemical feedbacks in the atmosphere. Here we apply a “state of the art” atmospheric chemistry transport model to show that large emissions of CH 4 would likely have an unexpectedly large impact on the chemical composition of the atmosphere and on radiative forcing (RF). The indirect contribution to RF of additional methane emission is particularly important. It is shown that if global methane emissions were to increase by factors of 2.5 and 5.2 above current emissions, the indirect contributions to RF would be about 250% and 400%, respectively, of the RF that can be attributed to directly emitted methane alone. Assuming several hypothetical scenarios of CH 4 release associated with permafrost thaw, shallow marine hydrate degassing, and submarine landslides, we find a strong positive feedback on RF through atmospheric chemistry. In particular, the impact of CH 4 is enhanced through increase of its lifetime, and of atmospheric abundances of ozone, stratospheric water vapor, and CO 2 as a result of atmospheric chemical processes. Despite uncertainties in emission scenarios, our results provide a better understanding of the feedbacks in the atmospheric chemistry that would amplify climate warming

    Gas and seismicity within the Istanbul seismic gap

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    Understanding micro-seismicity is a critical question for earthquake hazard assessment. Since the devastating earthquakes of Izmit and Duzce in 1999, the seismicity along the submerged section of North Anatolian Fault within the Sea of Marmara (comprising the “Istanbul seismic gap”) has been extensively studied in order to infer its mechanical behaviour (creeping vs locked). So far, the seismicity has been interpreted only in terms of being tectonic-driven, although the Main Marmara Fault (MMF) is known to strike across multiple hydrocarbon gas sources. Here, we show that a large number of the aftershocks that followed the M 5.1 earthquake of July, 25th 2011 in the western Sea of Marmara, occurred within a zone of gas overpressuring in the 1.5–5 km depth range, from where pressurized gas is expected to migrate along the MMF, up to the surface sediment layers. Hence, gas-related processes should also be considered for a complete interpretation of the micro-seismicity (~M < 3) within the Istanbul offshore domain

    A Consensus Genetic Map for Pinus taeda and Pinus elliottii and Extent of Linkage Disequilibrium in Two Genotype-Phenotype Discovery Populations of Pinus taeda

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    A consensus genetic map for Pinus taeda (loblolly pine) and Pinus elliottii (slash pine) was constructed by merging three previously published P. taeda maps with a map from a pseudo-backcross between P. elliottii and P. taeda. The consensus map positioned 3856 markers via genotyping of 1251 individuals from four pedigrees. It is the densest linkage map for a conifer to date. Average marker spacing was 0.6 cM and total map length was 2305 cM. Functional predictions of mapped genes were improved by aligning expressed sequence tags used for marker discovery to full-length P. taeda transcripts. Alignments to the P. taeda genome mapped 3305 scaffold sequences onto 12 linkage groups. The consensus genetic map was used to compare the genome-wide linkage disequilibrium in a population of distantly related P. taeda individuals (ADEPT2) used for association genetic studies and a multiple-family pedigree used for genomic selection (CCLONES). The prevalence and extent of LD was greater in CCLONES as compared to ADEPT2; however, extended LD with LGs or between LGs was rare in both populations. The average squared correlations, r2, between SNP alleles less than 1 cM apart were less than 0.05 in both populations and r2 did not decay substantially with genetic distance. The consensus map and analysis of linkage disequilibrium establish a foundation for comparative association mapping and genomic selection in P. taeda and P. elliottii.J.W.W. was supported by a USDA CSREES Food and Agricultural Sciences National Needs Graduate Fellowship. V.E.C. was supported by USDA NIFA Award #2011-68002-30185 (PINEMAP) and the USDA Forest Service. L.S.W. was supported by the National Science Foundation under grant no. ABI-1062432 to Indiana University. P.M.G., D.N., and K.M. were supported in part by USDA NIFA Award #2011-67009-30030 (PineRefSeq) to University of California, Davis.Peer reviewe

    A realist evaluation of the role of communities of practice in changing healthcare practice

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    <p>Abstract</p> <p>Background</p> <p>Healthcare organisations seeking to manage knowledge and improve organisational performance are increasingly investing in communities of practice (CoPs). Such investments are being made in the absence of empirical evidence demonstrating the impact of CoPs in improving the delivery of healthcare. A realist evaluation is proposed to address this knowledge gap. Underpinned by the principle that outcomes are determined by the context in which an intervention is implemented, a realist evaluation is well suited to understand the role of CoPs in improving healthcare practice. By applying a realist approach, this study will explore the following questions: What outcomes do CoPs achieve in healthcare? Do these outcomes translate into improved practice in healthcare? What are the contexts and mechanisms by which CoPs improve healthcare?</p> <p>Methods</p> <p>The realist evaluation will be conducted by developing, testing, and refining theories on how, why, and when CoPs improve healthcare practice. When collecting data, context will be defined as the setting in which the CoP operates; mechanisms will be the factors and resources that the community offers to influence a change in behaviour or action; and outcomes will be defined as a change in behaviour or work practice that occurs as a result of accessing resources provided by the CoP.</p> <p>Discussion</p> <p>Realist evaluation is being used increasingly to study social interventions where context plays an important role in determining outcomes. This study further enhances the value of realist evaluations by incorporating a social network analysis component to quantify the structural context associated with CoPs. By identifying key mechanisms and contexts that optimise the effectiveness of CoPs, this study will contribute to creating a framework that will guide future establishment and evaluation of CoPs in healthcare.</p
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