353 research outputs found

    2008src0764

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    Location of the active site for enzyme-adenylate formation in DNA ligases.

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    Crystal structures and proton dynamics in potassium and cesium hydrogen bistrifluoroacetate salts with strong symmetric hydrogen bonds

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    The crystal structures of potassium and cesium bistrifluoroacetates were determined at room temperature and at 20 K and 14 K, respectively, with the single crystal neutron diffraction technique. The crystals belong to the I2/a and A2/a monoclinic space groups, respectively, and there is no visible phase transition. For both crystals, the trifluoroacetate entities form dimers linked by very short hydrogen bonds lying across a centre of inversion. Any proton disorder or double minimum potential can be rejected. The inelastic neutron scattering spectral profiles in the OH stretching region between 500 and 1000 cm^{-1} previously published [Fillaux and Tomkinson, Chem. Phys. 158 (1991) 113] are reanalyzed. The best fitting potential has the major characteristics already reported for potassium hydrogen maleate [Fillaux et al. Chem. Phys. 244 (1999) 387]. It is composed of a narrow well containing the ground state and a shallow upper part corresponding to dissociation of the hydrogen bond.Comment: 31 pages, 7 figure

    Temporal Trends in the Standing Broad Jump Performance of United States Children and Adolescents

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    Purpose: To estimate temporal trends in broad jump performance for United States youth, a marker of muscular fitness and health. Method: Electronic databases, topical systematic reviews, and personal libraries were systematically searched for studies reporting descriptive standing broad jump data for apparently healthy United States youth (age 10–17 years). Temporal trends at the sex-age level were estimated using sample-weighted regression models associating the year of testing to mean jump performance, with national trends standardized to the year 1985 using a post-stratified population-weighting procedure. Results: Collectively, there was a small increase of 12.6 cm (95%CI: 12.5 to 12.7) or 7.9% (95%CI: 7.1 to 8.6) in 65,527 United States youth between 1911 and 1990. Increases were greater for girls (change in means [95% CI]: 17.1 cm [16.9 to 17.3]; 11.4% [10.7 to 12.2]) compared to boys (change in means [95% CI]: 8.5 cm [8.3 to 8.7]; 4.6% [3.8 to 5.4]), but did not differ between children (10–12 years) and adolescents (13–17 years). Increases in broad jump performance were not always uniform across time, with steady and progressive increases observed for boys and children, respectively, and a diminishing rate of increase observed for girls and adolescents. Conclusions: Muscular fitness is a good marker of health, so greater broad jump performance from 1911 to 1990 may reflect corresponding changes in health. Routine assessment of broad jump performance may be useful to monitor trends in health and muscular fitness of United States youth due to its practicality, scalability, and predictive utility

    Australia and Other Nations are Failing to Meet Sedentary Behaviour Guidelines for Children: Implications and a Way Forward

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    BACKGROUND: Australia has joined a growing number of nations which have evaluated the physical activity and sedentary behaviour status of their children. Australia received a 'D minus' in the first Active Healthy Kids Australia Physical Activity Report Card. METHODS: An expert subgroup of the Australian Report Card Research Working Group iteratively reviewed available evidence to answer three questions: 1) What are the main sedentary behaviours of children?, 2) What are the potential mechanisms for sedentary behaviour to impact on child health and development? and, 3) What are the effects of different types of sedentary behaviours on child health and development? RESULTS: Neither sedentary time nor screen time are homogeneous activities likely to result in homogenous effects. There are several mechanisms by which various sedentary behaviours may positively or negatively affect cardiometabolic, neuro-musculoskeletal, and psycho-social health, though the strength of evidence varies. National surveillance systems, and mechanistic, longitudinal and experimental studies are needed for Australia and other nations to improve their grade. CONCLUSIONS: Despite limitations, available evidence is sufficiently convincing that the total exposure and pattern of exposure to sedentary behaviours are critical to the healthy growth, development and wellbeing of children. Nations therefore need strategies to address these common behaviours

    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

    Evidence for methane in Martian meteorites

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    The putative occurrence of methane in the Martian atmosphere has had a major influence on the exploration of Mars, especially by the implication of active biology. The occurrence has not been borne out by measurements of atmosphere by the MSL rover Curiosity but, as on Earth, methane on Mars is most likely in the subsurface of the crust. Serpentinization of olivine-bearing rocks, to yield hydrogen that may further react with carbon-bearing species, has been widely invoked as a source of methane on Mars, but this possibility has not hitherto been tested. Here we show that some Martian meteorites, representing basic igneous rocks, liberate a methane-rich volatile component on crushing. The occurrence of methane in Martian rock samples adds strong weight to models whereby any life on Mars is/was likely to be resident in a subsurface habitat, where methane could be a source of energy and carbon for microbial activity

    Cardiorespiratory fitness is associated with physical literacy in a large sample of Canadian children aged 8 to 12 years

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    Background The associations between cardiorespiratory fitness (CRF) and physical literacy in children are largely unknown. The aim of this study was to assess the relationships between CRF, measured using the 20-m shuttle run test (20mSRT), and components of physical literacy among Canadian children aged 8–12 years. Methods A total of 9393 (49.9% girls) children, with a mean (SD) age of 10.1 (±1.2) years, from a cross-sectional surveillance study were included for this analysis. The SRT was evaluated using a standardized 15 m or 20 m protocol. All 15 m SRTs were converted to 20mSRT values using a standardized formula. The four domains of physical literacy (Physical Competence, Daily Behaviour, Motivation and Confidence, and Knowledge and Understanding) were measured using the Canadian Assessment of Physical Literacy. Tertiles were identified for 20mSRT laps, representing low, medium, and high CRF for each age and gender group. Cohen’s d was used to calculate the effect size between the low and high CRF groups. Results CRF was strongly and favourably associated with all components of physical literacy among school-aged Canadian children. The effect size between low and high CRF tertile groups was large for the Physical Competence domain (Cohen’s d range: 1.11–1.94) across age and gender groups, followed by moderate to large effect sizes for Motivation and Confidence (Cohen’s d range: 0.54–1.18), small to moderate effect sizes for Daily Behaviour (Cohen’s d range: 0.25–0.81), and marginal to moderate effect sizes for Knowledge and Understanding (Cohen’s d range: 0.08–0.70). Conclusions This study identified strong favourable associations between CRF and physical literacy and its constituent components in children aged 8–12 years. Future research should investigate the sensitivity and specificity of the 20mSRT in screening those with low physical literacy levels

    Successful strategies supporting recruitment, intervention delivery and retention targets in a randomized controlled trial of a complex intervention

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    Background: Complex interventions are widely used in modern health care practice and are defined as those having potentially interacting components. Evaluation can be challenging due to difficulties in logistics, standardisation and delivery. In addition, there can be difficulty recruiting to time and to target (particularly in multicentre studies) and minimising attrition and data loss. We report how the RAFT study [a seven-centre randomized controlled trial (RCT) comparing a complex group cognitive-behavioural (CB) intervention with standard care for the reduction of fatigue impact in patients with RA) is implementing successful strategies to meet recruitment, intervention delivery and retention targets. The study requires patients to make a substantial commitment over a 2 year period and for the intervention to be delivered by routine clinical staff trained for this purpose. Methods: The following strategies were agreed upon during the planning and design phase: Maximising recruitment: Funded research nurse time at all seven sites; mailshot option for approach; recruitment posters for clinics; flexible and pragmatic approach to session attendance; telephone, email and postal contact; newsletter and regular knowledge exchange between the central trial management team and sites; weekly recruitment updates and reviews. Ensuring intervention delivery: Flexible course dates and times set by each site, regular communication with the central management team to discuss foreseeable issues and preventative actions, provision of real-time clinical supervision and full-time telephone/email support. Minimising attrition and data loss: Primary outcome collection by telephone, ensuring regular personal contact; secondary data collection by postal questionnaire, reducing the number of hospital visits; telephone reminders; partial withdrawal options; personalized letters and thank you cards. Patient involvement: We had a number of acceptability and feasibility consultations with our two patient partners. Both partners had prior experience attending the intervention, were co-applicants on the grant proposal and continue to provide a patient perspective as members of the trial management group. Results: Our target was to recruit 300 participants with no recent medication changes and a fatigue level ≥6 (on a 1–10 scale where 10 is totally exhausted). During the 2 year recruitment phase, 333 participants were randomized (11% over target). All 28 programmes successfully delivered, with 7/7 sites and 14/15 tutors remaining fully engaged with the study. Retention at 6 months is currently 92.5% (sample size allows for 20% attrition). Data returned by those reaching the 6 month time point are 100% for the primary outcome and 97% for secondary outcomes. Conclusion: Advanced planning and consistent application of these strategies has ensured success so far. A flexible and pragmatic approach, regular communication between local and central teams, personal contact with participants and extensive patient partner input are key components

    Cognitive Therapy for Reducing The Impact of Rheumatoid Arthritis Fatigue: Sucessful Strategies for Meeting Targets in A Complex Health Care Intervention

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    Background: Complex interventions are widely used in modern health care practice and are defined as those having potentially interacting components. Evaluation can be challenging due to difficulties in logistics, standardisation, delivery, recruiting to time and target (particularly in multi-centre studies) and minimising attrition and data loss.We report how the RAFT study (a 7-centre randomised controlled trial comparing a complex, group cognitive-behavioural intervention with standard care, for the reduction of fatigue impact in patients with rheumatoid arthritis) is implementing successful strategies to meet targets. The study requires patients to make a substantial commitment over a two year period and for the intervention to be delivered by routine clinical staff trained for this purpose.Objectives: To recruit to time and target, ensure intervention delivery, minimise attrition and maximise retention.Methods: Maximising recruitment: Funded research nurse time at all 7 sites, mailshot approach option, recruitment posters, flexible/pragmatic approach to session attendance, telephone, email and postal contact, newsletter and regular knowledge exchange between the central management team and sites, weekly recruitment review. Ensuring intervention delivery: Flexible course dates and times, regular discussions around foreseeable issues and preventative actions, provision of real-time clinical supervision and full-time telephone/email support. Minimising attrition and data loss: Primary outcome collected by telephone ensuring regular personal contact. Secondary data collected by postal questionnaire reducing the number of hospital visits. Telephone reminders, partial withdrawal options, personalised letters and thank you cards. Patient involvement: Acceptability and feasibility consultations with our 2 patient partners. Both have experience of attending the intervention, were co-applicants on the grant proposal and continue to provide the patient perspective as members of the trial management group.Results: Recruitment: Target of 300 participants with no recent medication changes and a fatigue level of ≥6 (on a 1–10 scale where 10 is totally exhausted). During the 2 year recruitment phase 333 participants were randomised (11% over target). Intervention delivery: 28/28 programmes successfully delivered with 7/7 sites and 14/15 tutors remaining fully engaged with the study. Attrition and data loss: Retention at 6 months is currently 92.5% (sample size allows for 20% attrition). Data returned by those reaching the 6 month time point is 100% for the primary outcome and 97% for secondary outcomes.Conclusions: Advanced planning and consistent application of these strategies has ensured success so far. A flexible and pragmatic approach, regular communication between local and central teams, personal contact with participants and extensive patient partner input are key components
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