264 research outputs found

    Stressor reflections, sleep, and psychological well-being: A pre-registered experimental test of self-distanced versus self-immersed reflections

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    This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: All data and analysis code are publicly available via our OSF project (https://osf.io/ue9jm/). We pre-registered the design and analysis plan for this experiment via the OSF (https://osf.io/jyf69). Deviations from our registered protocol are reported in the manuscript in the section ‘Deviations from Pre-Registered Protocol’.Evidence supports the effectiveness of cuing people to analyse negative autobiographical experiences from self-distanced rather than self-immersed perspectives. However, the evidence on which this expectation resides is limited largely to static snapshots of mean levels of cognitive and emotional factors. Via a pre-registered, randomised controlled trial (N = 257), we examined the differential effectiveness of self-distanced relative to self-immersed reflections on mean levels and within-person variability of sleep duration and quality as well as psychological well-being over a 5-day working week. Except for sleep quality, we found that reflecting from a psychologically distanced perspective, overall, was no more effective for mean levels and within-person variability of sleep duration, well-being, and stress-related factors than when the current self is fully immersed in the experiential reality of the event. We consider several substantive and methodological considerations (e.g., dosage, salience of stressor event) that require interrogation in future research via experimental and longitudinal observational methods

    Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

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    Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

    Integration of Women Veterans into VA Quality Improvement Research Efforts: What Researchers Need to Know

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    The Department of Veterans Affairs (VA) and other federal agencies require funded researchers to include women in their studies. Historically, many researchers have indicated they will include women in proportion to their VA representation or pointed to their numerical minority as justification for exclusion. However, women’s participation in the military—currently 14% of active military—is rapidly changing veteran demographics, with women among the fastest growing segments of new VA users. These changes will require researchers to meet the challenge of finding ways to adequately represent women veterans for meaningful analysis. We describe women veterans’ health and health-care use, note how VA care is organized to meet their needs, report gender differences in quality, highlight national plans for women veterans’ quality improvement, and discuss VA women’s health research. We then discuss challenges and potential solutions for increasing representation of women veterans in VA research, including steps for implementation research

    Farmer-Scientist Knowledge Exchange

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    The last 25 years has seen a paradigm shift in the understanding of the nature of knowledge and how it is exchanged in the agricultural context. A changing backdrop, with the move towards multi-functional land management, persistent environmental problems and the search for sustainable agricultural approaches, has brought new challenges. At the same time the research agenda on knowledge has changed as an era of positivism, during which science and scientific experts were given unrivalled authority, was challenged by social studies of science that began to question the superiority of scientific knowledge, and value alternative forms of knowledge such as those held by farmers. Theory and practice of knowledge exchange in agriculture has evolved in line with this, shifting from a linear model of knowledge transfer to a perspective that integrates knowledge from multiple actors through facilitation and participation and emphasises learning in a social context

    Rgs2 Mediates Pro-Angiogenic Function of Myeloid Derived Suppressor Cells in the Tumor Microenvironment via Upregulation of MCP-1

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    Tumor growth is intimately linked with stromal interactions. Myeloid derived suppressor cells (MDSCs) are dramatically elevated in cancer patients and tumor bearing mice. MDSCs modulate the tumor microenvironment through attenuating host immune response and increasing vascularization.In searching for molecular mediators responsible for pro-tumor functions, we found that regulator of G protein signaling-2 (Rgs2) is highly increased in tumor-derived MDSCs compared to control MDSCs. We further demonstrate that hypoxia, a common feature associated with solid tumors, upregulates the gene expression. Genetic deletion of Rgs2 in mice resulted in a significant retardation of tumor growth, and the tumors exhibit decreased vascular density and increased cell death. Interestingly, deletion of Rgs2 in MDSCs completely abolished their tumor promoting function, suggesting that Rgs2 signaling in MDSCs is responsible for the tumor promoting function. Cytokine array profiling identified that Rgs2-/- tumor MDSCs produce less MCP-1, leading to decreased angiogenesis, which could be restored with addition of recombinant MCP-1.Our data reveal Rgs2 as a critical regulator of the pro-angiogenic function of MDSCs in the tumor microenvironment, through regulating MCP-1 production

    Recent evolution of the NF-κB and inflammasome regulating protein POP2 in primates

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    <p>Abstract</p> <p>Background</p> <p>Pyrin-only protein 2 (POP2) is a small human protein comprised solely of a pyrin domain that inhibits NF-κB p65/RelA and blocks the formation of functional IL-1β processing inflammasomes. Pyrin proteins are abundant in mammals and several, like POP2, have been linked to activation or regulation of inflammatory processes. Because <it>POP2 </it>knockout mice would help probe the biological role of inflammatory regulation, we thus considered whether <it>POP2 </it>is common in the mammalian lineage.</p> <p>Results</p> <p>BLAST searches revealed that <it>POP2 </it>is absent from the available genomes of not only mice and rats, but those of other domestic mammals and New World monkeys as well. <it>POP2 </it>is however present in the genome of the primate species most closely related to humans including <it>Pan troglodytes </it>(chimpanzees), <it>Macaca mulatta </it>(rhesus macaques) and others. Interestingly, chimpanzee POP2 is identical to human POP2 (huPOP2) at both the DNA and protein level. Macaque POP2 (mqPOP2), although highly conserved is not identical to the human sequence; however, both functions of the human protein are retained. Further, <it>POP2 </it>appears to have arisen in the mammalian genome relatively recently (~25 mya) and likely derived from retrogene insertion of <it>NLRP2</it>.</p> <p>Conclusion</p> <p>Our findings support the hypothesis that the NLR loci of mammals, encoding proteins involved in innate and adaptive immunity as well as mammalian development, have been subject to recent and strong selective pressures. Since POP2 is capable of regulating signaling events and processes linked to innate immunity and inflammation, its presence in the genomes of hominids and Old World primates further suggests that additional regulation of these signals is important in these species.</p

    Nutrients cause grassland biomass to outpace herbivory

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    Human activities are transforming grassland biomass via changing climate, elemental nutrients, and herbivory. Theory predicts that food-limited herbivores will consume any additional biomass stimulated by nutrient inputs ('consumer-controlled'). Alternatively, nutrient supply is predicted to increase biomass where herbivores alter community composition or are limited by factors other than food ('resource-controlled'). Using an experiment replicated in 58 grasslands spanning six continents, we show that nutrient addition and vertebrate herbivore exclusion each caused sustained increases in aboveground live biomass over a decade, but consumer control was weak. However, at sites with high vertebrate grazing intensity or domestic livestock, herbivores consumed the additional fertilization-induced biomass, supporting the consumer-controlled prediction. Herbivores most effectively reduced the additional live biomass at sites with low precipitation or high ambient soil nitrogen. Overall, these experimental results suggest that grassland biomass will outstrip wild herbivore control as human activities increase elemental nutrient supply, with widespread consequences for grazing and fire risk
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