821 research outputs found

    Measurement of GEp/GMp in ep -> ep to Q2 = 5.6 GeV2

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    The ratio of the electric and magnetic form factors of the proton, GEp/GMp, was measured at the Thomas Jefferson National Accelerator Facility (JLab) using the recoil polarization technique. The ratio of the form factors is directly proportional to the ratio of the transverse to longitudinal components of the polarization of the recoil proton in the elastic epep\vec ep \to e\vec p reaction. The new data presented in this article span the range 3.5 < Q2 < 5.6 GeV2 and are well described by a linear Q2 fit. Also, the ratio QF2p/F1p reaches a constant value above Q2=2 GeV2.Comment: 6 pages, 4 figures Added two names to the main author lis

    Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

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    Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

    Display of probability densities for data from a continuous distribution

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    Based on cumulative distribution functions, Fourier series expansion and Kolmogorov tests, we present a simple method to display probability densities for data drawn from a continuous distribution. It is often more efficient than using histograms.Comment: 5 pages, 4 figures, presented at Computer Simulation Studies XXIV, Athens, GA, 201

    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

    Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

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    Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified

    The transfer and fate of Pb from sewage sludge amended soil in a multi-trophic food chain: a comparison with the labile elements Cd and Zn

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    The contamination of agroecosystems due to the presence of trace elements in commonly used agricultural materials is a serious issue. The most contaminated material is usually sewage sludge, and the sustainable use of this material within agriculture is a major concern. This study addresses a key issue in this respect, the fate of trace metals applied to soil in food chains. The work particularly addresses the transfer of Pb, which is an understudied element in this respect, and compares the transfer of Pb with two of the most labile metals, Cd and Zn. The transfer of these elements was determined from sludge-amended soils in a food chain consisting of Indian mustard (Brassica juncea), the mustard aphid (Lipaphis erysimi) and a predatory beetle (Coccinella septempunctata). The soil was amended with sludge at rates of 0, 5, 10 and 20 % (w/w). Results showed that Cd was readily transferred through the food chain until the predator trophic level. Zn was the most readily transferred element in the lower trophic levels, but transfer to aphids was effectively restricted by the plant regulating shoot concentration. Pb had the lowest level of transfer from soil to shoot and exhibited particular retention in the roots. Nevertheless, Pb concentrations were significantly increased by sludge amendment in aphids, and Pb was increasingly transferred to ladybirds as levels increased. The potential for Pb to cause secondary toxicity to organisms in higher trophic levels may have therefore been underestimated

    Adherence to Actigraphic Devices in Elementary School-Aged Children:Systematic Review and Meta-Analysis

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    BACKGROUND: Consistent wear is essential for valid and reliable actigraphy data. Adherence to actigraphy may be challenging in primary school children due to developmental and design considerations, yet no quantitative synthesis of adherence in this age group exists.OBJECTIVE: The aim of this study was to provide the first pooled estimate of actigraphy adherence in primary school-aged children and examine the impact of individual, device, and study-specific factors on adherence.METHODS: We searched seven electronic databases for studies reporting adherence to actigraphy in primary school-aged children. Searches were conducted in Embase, MEDLINE, PsycINFO, Social Policy and Practice via OVID, Education Resources Information Center, British Education Index, and CINAHL via EBSCO using database-specific search strategies conducted between January 2018 and January 24, 2023. Forward and backward citation searches were completed on the Web of Science Core Collection and Google Scholar. Gray literature searches were undertaken in PsycEXTRA and Healthcare Management Information Consortium. Empirical studies reporting quantitative data on adherence to community-based actigraphy in children aged 5-11 years (or if ≥50% of the average age fell within this range) were included. Eligible studies were written in English and could be published or unpublished. Risk of bias was assessed using an 8-item checklist adapted from Berger et al's actigraphy reporting standards. All included studies were narratively synthesized, and adherence data were pooled in a proportional meta-analysis. Adherence was calculated as the proportion of children meeting wear-time criteria to be included in the analysis compared to the number of children invited to use the device at baseline. Meta-regression was used to examine the impact of individual, device, and study-specific factors on adherence. Prediction intervals were calculated to estimate the range of adherence expected across future studies.RESULTS: Data were extracted from 235 studies (N=148,161); of these, 135 studies (n=64,541) provided adherence data for proportional meta-analysis. Pooled adherence, measured across 1-140 days, was 81.6% (95% CI 78.7%-84.4%; I2=98.8%). The prediction intervals (42.8%-100%) indicated substantial variability in adherence estimates across studies. Meta-regression suggested that individual characteristics contributed to observed heterogeneity as children with a physical health diagnosis (b=0.236, 95% CI 0.009-0.464; P=.04) and those with neurodevelopmental or mental health diagnosis (b=0.395, 95% CI 0.125-0.665; P=.004) demonstrated higher adherence than undiagnosed children, though these effects were of modest magnitude. No significant effects were found for age, placement, protocol length, protocol deviation, or incentivization. Reporting quality was poor, with only 3.4% of studies satisfying all criteria.CONCLUSIONS: This review demonstrates generally high actigraphy adherence in primary school-aged children, particularly those with health conditions. However, observed variability indicates that adherence was much lower in some contexts, underscoring that the reported pooled adherence cannot be assumed across future actigraphy applications within this age group. Future research should use standardized adherence reporting and should plan for adherence variability.</p

    History of clinical transplantation

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    The emergence of transplantation has seen the development of increasingly potent immunosuppressive agents, progressively better methods of tissue and organ preservation, refinements in histocompatibility matching, and numerous innovations is surgical techniques. Such efforts in combination ultimately made it possible to successfully engraft all of the organs and bone marrow cells in humans. At a more fundamental level, however, the transplantation enterprise hinged on two seminal turning points. The first was the recognition by Billingham, Brent, and Medawar in 1953 that it was possible to induce chimerism-associated neonatal tolerance deliberately. This discovery escalated over the next 15 years to the first successful bone marrow transplantations in humans in 1968. The second turning point was the demonstration during the early 1960s that canine and human organ allografts could self-induce tolerance with the aid of immunosuppression. By the end of 1962, however, it had been incorrectly concluded that turning points one and two involved different immune mechanisms. The error was not corrected until well into the 1990s. In this historical account, the vast literature that sprang up during the intervening 30 years has been summarized. Although admirably documenting empiric progress in clinical transplantation, its failure to explain organ allograft acceptance predestined organ recipients to lifetime immunosuppression and precluded fundamental changes in the treatment policies. After it was discovered in 1992 that long-surviving organ transplant recipient had persistent microchimerism, it was possible to see the mechanistic commonality of organ and bone marrow transplantation. A clarifying central principle of immunology could then be synthesized with which to guide efforts to induce tolerance systematically to human tissues and perhaps ultimately to xenografts
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