726 research outputs found

    Randomised controlled trial comparing daily VerSus depot vitamin D3 therapy in 0-16-year-old newly settled refugees in Western Australia over a period of 40 weeks

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    Vitamin D deficiency is highly prevalent in newly settled refugees in Western Australia (WA). If adherence to daily vitamin D therapy is problematic, depot therapy is a therapeutic alternative. The aim of this studywas to compare daily versus depot treatment and factors influencing the therapeutic outcome. Newly settled refugees (n = 151) with 25(OH)D levels less than 78 nmol/L were randomised to receive daily or depot vitamin D therapy with eight weekly interval follow up to 40 weeks. Biochemical and clinical parameters were collected at each visit. Generalized LinearMixedModels (GLMM) examined the longitudinal changes over time controlling for confounders including age, gender, treatment arm, season, country of refuge/origin and sun exposure score. Participants were aged 5.5 months to 16.0 years (75 males, 83 females). Both treatment groups achieved vitamin D sufficiency. The daily treatment group had significantly higher 25(OH)D levels at each visit post baseline and a higher proportion of participants with levels above 50 nmol/L at all time points. Time, treatment group, calcium and sun exposure score were significant predictors of 25(OH)D serum levels. Depot vitamin D therapy is an alternative to daily treatment in this at-risk group of children and adolescents in whom treatment adherence is problemati

    Effects of Ultraviolet Radiation on Amphibians: Field Experiments

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    Numerous reports suggest that populations of amphibians from a wide variety of locations are experiencing population declines and/or range reductions. In some cases, unusually high egg mortality has been reported. Field experiments have been used with increasing frequency to investigate ultraviolet radiation as one of the potential factors contributing to these declines. Results from field experiments illustrate that hatching success of eggs is hampered by ultraviolet radiation in a number of species, while other species appear to be unaffected. Continued mortality in early life-history stages may ultimately contribute to a population decline. Although UV-B radiation may not contribute to the population declines of all species, it may play a role in the population decline of some species, especially those that lay eggs in open shallow water subjected to solar radiation and in those that have a poor ability to repair UV-induced DNA damage.Peer reviewe

    The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer

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    Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57(Kip2) as specifically downregulated in carboplatin resistance. Presently, we describe confirmation of these preliminary data with a variety of approaches

    Living in a risky world: the onset and ontogeny of an integrated antipredator phenotype in a coral reef fish

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    Prey individuals with complex life-histories often cannot predict the type of risk environment to which they will be exposed at each of their life stages. Because the level of investment in defences should match local risk conditions, we predict that these individuals should have the ability to modulate the expression of an integrated defensive phenotype, but this switch in expression should occur at key life-history transitions. We manipulated background level of risk in juvenile damselfish for four days following settlement (a key life-history transition) or 10 days post-settlement, and measured a suite of physiological and behavioural variables over 2 weeks. We found that settlement-stage fish exposed to high-risk conditions displayed behavioural and physiological alterations consistent with high-risk phenotypes, which gave them a survival advantage when exposed to predators. These changes were maintained for at least 2 weeks. The same exposure in post-settlement fish failed to elicit a change in some traits, while the expression of other traits disappeared within a week. Our results are consistent with those expected from phenotypic resonance. Expression of antipredator traits may be masked if individuals are not exposed to certain conditions at key ontogenetic stages

    Biomechanical analysis of the penalty-corner drag-flick of elite male and female hockey players

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    The aim of this study was to analyse the kinematic sequencing in the penalty-corner drag-flicks of elite male and female field hockey players of international calibre. Thirteen participants (one skilled male drag-flicker and six male and six female elite players) participated in the study. An optoelectronic motion analysis system was used to capture the drag-flicks with six cameras, sampling at 250 Hz. Select ground reaction force parameters were obtained from a force platform which registered the last support of the front foot. Twenty trials were captured from each subject. Both player groups showed significantly (p < 0.05) smaller ball velocity at release, peak angular velocity of the pelvis, and negative and positive peak angular velocities of the stick than the skilled subject. Normalised ground reaction forces of the gender groups were also smaller than that of the skilled drag-flicker. By comparing these players we established that the cues of the skill level are a wide stance, a whipping action (rapid back lift) of the stick followed by an explosive sequential movement of the pelvis, upper trunk and stick

    DNA repair and resistence to UV-B radiation in western spotted frogs

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    assessed DNA repair and resistance to solar radiation in eggs of members of the western spotted frog complex (Rana pretiosa and R. luteiventris), species whose populations are suffering severe range reductions and declines. Specifically, we measured the activity of photoreactivating enzyme (photolyase) in oocytes of spotted frogs. In some species, photoreactivation is the most important mechanism for repair of UV-damaged DNA. Using field experiments, we also compared the hatching success of spotted frog embr yos at natural oviposition sites at three elevations, where some embr yos were subjected to ambient levels of UV-B radiation and others were shielded from UV-B radiation. Compared with other amphibians, photolyase activities in spotted frogs were relatively high. At all sites, hatching success was unaffected by UV-B. Our data support the interpretation that amphibian embr yos with relatively high levels of photolyase are more resistant to UV-B radiation than those with lower levels of photolyase. At the embr yonic stage, UV-B radiation does not presently seem to be contributing to the population declines of spotted frogs.Peer reviewe

    Investigating Europa’s Habitability with the Europa Clipper

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    The habitability of Europa is a property within a system, which is driven by a multitude of physical and chemical processes and is defined by many interdependent parameters, so that its full characterization requires collaborative investigation. To explore Europa as an integrated system to yield a complete picture of its habitability, the Europa Clipper mission has three primary science objectives: (1) characterize the ice shell and ocean including their heterogeneity, properties, and the nature of surface–ice–ocean exchange; (2) characterize Europa’s composition including any non-ice materials on the surface and in the atmosphere, and any carbon-containing compounds; and (3) characterize Europa’s geology including surface features and localities of high science interest. The mission will also address several cross-cutting science topics including the search for any current or recent activity in the form of thermal anomalies and plumes, performing geodetic and radiation measurements, and assessing high-resolution, co-located observations at select sites to provide reconnaissance for a potential future landed mission. Synthesizing the mission’s science measurements, as well as incorporating remote observations by Earth-based observatories, the James Webb Space Telescope, and other space-based resources, to constrain Europa’s habitability, is a complex task and is guided by the mission’s Habitability Assessment Board (HAB)

    Strong negative self regulation of Prokaryotic transcription factors increases the intrinsic noise of protein expression

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    Background Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative self regulation of transcription in regulating the variability of protein abundance using a variety of stochastic modeling techniques. Results We undertake a novel analysis of a classic model for negative self regulation. We demonstrate that, with standard approximations, protein variance relative to its mean should be independent of repressor strength in a physiological range. Consequently, in that range, the coefficient of variation would increase with repressor strength. However, stochastic computer simulations demonstrate that there is a greater increase in noise associated with strong repressors than predicted by theory. The discrepancies between the mathematical analysis and computer simulations arise because with strong repressors the approximation that leads to Michaelis-Menten-like hyperbolic repression terms ceases to be valid. Because we observe that strong negative feedback increases variability and so is unlikely to be a mechanism for noise control, we suggest instead that negative feedback is evolutionarily favoured because it allows the cell to minimize mRNA usage. To test this, we used in silico evolution to demonstrate that while negative feedback can achieve only a modest improvement in protein noise reduction compared with the unregulated system, it can achieve good improvement in protein response times and very substantial improvement in reducing mRNA levels. Conclusions Strong negative self regulation of transcription may not always be a mechanism for homeostatic control of protein abundance, but instead might be evolutionarily favoured as a mechanism to limit the use of mRNA. The use of hyperbolic terms derived from quasi-steady-state approximation should also be avoided in the analysis of stochastic models with strong repressors
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