470 research outputs found

    Emerging collaborative research platforms for the next generation of physical activity, sleep and exercise medicine guidelines : the Prospective Physical Activity, Sitting, and Sleep consortium (ProPASS)

    Get PDF
    Galileo Galilei’s quote “measure what is measurable, and make measurable what is not so” has particular relevance to health behaviours, such as physical activity (PA), sitting and sleep, whose measurement during free living is notoriously difficult. To date, much of what we know about how these behaviours affect our health is based on self-report by questionnaires which have limited validity, are prone to bias, and inquire about selective aspects of these behaviours. Although self-reported evidence has made great contributions to shaping public health and exercise medicine policy and guidelines until now1, the ongoing advancements of accelerometry-based measurement and evidence synthesis methods are set to change the landscape. The aim of this editorial is to outline new directions in PA and sleep related epidemiology that open new horizons for guideline development and improvement; and to describe a new research collaboration platform: the Prospective Physical Activity, Sitting, and Sleep consortium (ProPASS)

    Magnetism, FeS colloids, and Origins of Life

    Full text link
    A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via physicalphysical interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

    Transcriptional Activation of REST by Sp1 in Huntington's Disease Models

    Get PDF
    In Huntington's disease (HD), mutant huntingtin (mHtt) disrupts the normal transcriptional program of disease neurons by altering the function of several gene expression regulators such as Sp1. REST (Repressor Element-1 Silencing Transcription Factor), a key regulator of neuronal differentiation, is also aberrantly activated in HD by a mechanism that remains unclear. Here, we show that the level of REST mRNA is increased in HD mice and in NG108 cells differentiated into neuronal-like cells and expressing a toxic mHtt fragment. Using luciferase reporter gene assay, we delimited the REST promoter regions essential for mHtt-mediated REST upregulation and found that they contain Sp factor binding sites. We provide evidence that Sp1 and Sp3 bind REST promoter and interplay to fine-tune REST transcription. In undifferentiated NG108 cells, Sp1 and Sp3 have antagonistic effect, Sp1 acting as an activator and Sp3 as a repressor. Upon neuronal differentiation, we show that the amount and ratio of Sp1/Sp3 proteins decline, as does REST expression, and that the transcriptional role of Sp3 shifts toward a weak activator. Therefore, our results provide new molecular information to the transcriptional regulation of REST during neuronal differentiation. Importantly, specific knockdown of Sp1 abolishes REST upregulation in NG108 neuronal-like cells expressing mHtt. Our data together with earlier reports suggest that mHtt triggers a pathogenic cascade involving Sp1 activation, which leads to REST upregulation and repression of neuronal genes

    Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection

    Get PDF
    Antiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal infection. HIV-1 gag, pol and nef sequences were generated from a historical repository of longitudinal specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for each gene and in CTL-restricted and non-restricted epitopes. Evolutionary rate was higher in nef and gag vs. pol, and lower in infants with non-severe immunosuppression vs. severe immunosuppression across gag and nef. Selection pressure was stronger in infants with non-severe immunosuppression vs. severe immunosuppression across gag. The analysis also showed that infants with non-severe immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in gag and nef. Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data indicate that infant CTLs can exert selection pressure on gag and nef epitopes in early infection and that stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results have implications for the development of paediatric HIV-1 vaccines

    Direct observations of the effect of fine sediment deposition on the vertical movement of Gammarus pulex (Amphipoda: Gammaridae) during substratum drying

    Get PDF
    Benthic macroinvertebrates inhabit the streambed sediments of temporary streams during drying events. Fine sediment (< 2 mm in diameter) deposition and clogging of interstitial pathways reduces the connectivity between benthic and subsurface habitats, potentially inhibiting macroinvertebrate vertical movements. Direct observations within subsurface sediments are, however, inherently difficult. As a result, confirmation of macroinvertebrate vertical movement, and the effect of fine sediment, is limited. We used laboratory mesocosms containing transparent gravel sized particles (10–15 mm) to facilitate the direct observation and tracking of vertical movements by Gammarus pulex in response to water level reduction and sedimentation. Seven sediment treatments comprised two fine sediment fractions (small: 0.125–0.5 mm, coarse sand: 0.5–1 mm) deposited onto the surface of the substrate, and a control treatment where no fine sediment was applied. We found that G. pulex moved into the subsurface gravel sediments in response to drying, but their ability to remain submerged during water level reduction was impeded by fine sediment deposition. In particular deposition of the coarser sand fraction clogged the sediment surface, limiting vertical movements. Our results highlight the potential effect of sedimentation on G. pulex resistance to drying events in streams
    • …
    corecore