70 research outputs found

    The worlds of rural children : deconstructing adult discourses of the rural.

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    SIGLEAvailable from British Library Document Supply Centre-DSC:DXN019477 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

    Variability of the Subtropical Front in the Tasman Sea

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    The subtropical front (STF) is a fundamental feature of the Southern Ocean. It separates waters in the subtropical gyres from Subantarctic waters. At present however only a rudimentary understanding exists about its temporal variability. Variations in the physical state of the STF (i.e. its location, intensity and hydrography) have implications for atmospheric circulation, marine productivity and climate. This thesis focuses on improving temporal understanding of this major Southern Ocean front. Observations of the temporal variability of the STF in the Tasman Sea are presented. These are obtained through a synthesis of repeat hydrographic sections and remotely sensed sea surface temperature (SST) and sea surface salinity (SSS) data. This work aims to contribute to an improved understanding of how the physical state of the STF varies in time, and of role that topography and surface winds play in this variability. Using three hydrographic surveys and remotely sensed SST data collected during the austral autumns of 2007, 2008 and 2011, the interaction of the south subtropical front (S-STF) with topography around southern New Zealand is investigated. The poleward limit of the S-STF is found to be remarkably consistent, crossing the Macquarie Ridge north of a seamount at 49.6°S, before turning equatorward east of 166°E to follow the upper continental shelf. This is contrary to some previous descriptions that placed the S-STF lying across the Snares Shelf close to 47.5°S. Cross-frontal temperature and salinity gradients at the S-STF are also found to be intensified in regions of shallow bathymetry. Both results are attributed to topographic steering of the S-STF by bathymetry at approximately 500 m depth. Thermal fronts detected using thirty years (1982-2011) of remotely sensed SST data are combined with 27 months (2013-2015) of remotely sensed SSS data, to provide new insights on the typical position and seasonal migration of the S-STF in the Tasman Sea. By examining thirty year annual-mean and seasonal-mean distributions of hundreds of thermal fronts that are identified as likely to be surface expressions of the S-STF, a long-term, statistical view of the S-STF’s position in the western and eastern Tasman Sea is developed. It is apparent that seasonal migrations of the S-STF in these locations do not exceed 1°, contrary to a recent suggestion that the subtropical frontal zone undergoes a global, seasonal shift of 5-7°. The distributions of thermal fronts also contain an intriguing suggestion that the S-STF might behave bimodally at the Macquarie Ridge. SSTs across the S-STF south of New Zealand exhibit marked interannual variability. SST variability in this region may have significant impacts on regional climate. Recent studies have shown that variability in the basin-wide wind stress curl significantly influence SSTs in other parts of the South Pacific subtropical gyre. Using thirty years of remotely sensed SST and atmospheric reanalysis data, variability of subtropical and Subantarctic SSTs at the S-STF south of New Zealand are found to be significantly lag-correlated to both basin-wide and local-scale winds. Potential mechanisms linking SST with variations in the South Pacific wind field are also discussed

    European Survey on Scholarly Practices and Digital Needs in the Arts and Humanities

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    This report summarizes the statistical analysis of the findings of a web-based survey conducted by the Digital Methods and Practices Observatory (DiMPO), a working group under VCC2 of the DARIAH research infrastructure (Digital Research Infrastructure for the Arts and Humanities). In order to provide an evidence-based, up-to-date, and meaningful account of the emerging information practices, needs and attitudes of arts and humanities researchers in the evolving European digital scholarly environment, the web survey involved a transnational team of researchers from more than a dozen countries, and addressed digitally-enabled research practices, attitudes and needs in all areas of Europe and across different arts and humanities disciplines and contexts

    Stabilization of urinary microRNAs by association with exosomes and argonaute 2 protein

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    A pressing need for new chronic kidney disease (CKD) biomarkers persists. MicroRNAs (miRNAs) are emerging as a novel class of disease biomarkers in body fluids, but mechanisms conferring their stability in urine have not been fully elucidated. Here we investigated stabilization in human urine of ubiquitously expressed miR-16, and miR-192, which we have shown previously to be downregulated in renal fibrosis, by association with extracellular vesicles and with argonaute protein (AGO) 2. Endogenous urinary miR-16 was significantly more resistant to RNase-mediated degradation than exogenous, spiked-in, Caenorhabditis elegans cel-miR-39. We used our previously optimized high-resolution exosome isolation protocol with sucrose gradient ultracentrifugation to sub-fractionate the primary extracellular vesicle-rich urinary pellet. MiR-16 and miR-192 were enriched in exosomal sucrose gradient fractions, but were also detected in all other fractions. This suggested association of urinary miRNAs with other urinary extracellular vesicles and/or pellet components, complicating previous estimates of miRNA:exosome stoichiometry. Proteinase K digestion destabilized urinary miR-16 and we showed, for the first time, RNA-immunoprecipitation of urinary miR-16:AGO2 and miR-192:AGO2 complexes. Association with exosomes and AGO2 stabilized urinary miR-16 and miR-192, suggesting quantitative urinary miRNA analysis has the potential to identify novel, non-invasive CKD biomarkers

    Novel missense mutations in the glycine receptor β subunit gene (GLRB) in startle disease

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    Startle disease is a rare, potentially fatal neuromotor disorder characterized by exaggerated startle reflexes and hypertonia in response to sudden unexpected auditory, visual or tactile stimuli. Mutations in the GlyR alpha(1) subunit gene (GLRA1) are the major cause of this disorder, since remarkably few individuals with mutations in the GlyR beta subunit gene (GLRB) have been found to date. Systematic DNA sequencing of GLRB in individuals with hyperekplexia revealed new missense mutations in GLRB, resulting in M177R, L285R and W310C substitutions. The recessive mutation M177R results in the insertion of a positively-charged residue into a hydrophobic pocket in the extracellular domain, resulting in an increased EC50 and decreased maximal responses of alpha(1)beta GlyRs. The de novo mutation L285R results in the insertion of a positively-charged side chain into the pore-lining 9' position. Mutations at this site are known to destabilize the channel closed state and produce spontaneously active channels. Consistent with this, we identified a leak conductance associated with spontaneous GlyR activity in cells expressing alpha(1)beta(L285R) GlyRs. Peak currents were also reduced for alpha(1)beta(L285R) GlyRs although glycine sensitivity was normal. W310C was predicted to interfere with hydrophobic side-chain stacking between M1, M2 and M3. We found that W310C had no effect on glycine sensitivity, but reduced maximal currents in alpha(1)beta GlyRs in both homozygous (alpha(1)beta(W310C)) and heterozygous (alpha(1)beta beta(W310C)) stoichiometries. Since mild startle symptoms were reported in W310C carriers, this may represent an example of incomplete dominance in startle disease, providing a potential genetic explanation for the 'minor' form of hyperekplexia. (C) 2012 Elsevier Inc. All rights reserved

    Autosub Long Range 1500: A continuous 2000 km field trial

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    Long Range Autonomous Underwater Vehicles (LRAUVs) offer the potential to monitor the ocean at higher spatial and temporal resolutions compared to conventional ship-based techniques. The multi-week to multi-month endurance of LRAUVs enables them to operate independently of a support vessel, creating novel opportunities for ocean observation. The National Oceanography Centre’s Autosub Long Range is one of a small number of vehicles designed for a multi-month endurance. The latest iteration, Autosub Long Range 1500 (ALR1500), is a 1500 m depth-rated LRAUV developed for ocean science in coastal and shelf seas or in the epipelagic and meteorologic regions of the ocean. This paper presents the design of the ALR1500 and results from a five week continuous deployment from Plymouth, UK, to the continental shelf break and back again, a distance of approximately 2000km which consumed half of the installed energy. The LRAUV was unaccompanied throughout the mission and operated continuously beyond visual line of sight

    Intended Consequences Statement in Conservation Science and Practice

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    As the biodiversity crisis accelerates, the stakes are higher for threatened plants and animals. Rebuilding the health of our planet will require addressing underlying threats at many scales, including habitat loss and climate change. Conservation interventions such as habitat protection, management, restoration, predator control, trans location, genetic rescue, and biological control have the potential to help threatened or endangered species avert extinction. These existing, well-tested methods can be complemented and augmented by more frequent and faster adoption of new technologies, such as powerful new genetic tools. In addition, synthetic biology might offer solutions to currently intractable conservation problems. We believe that conservation needs to be bold and clear-eyed in this moment of great urgency

    Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

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    Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.Published versionThe authors thank the UK MS Society for financial support (grant number: C008-16.1). DRO was funded by an MRC Clinician Scientist Award (MR/N008219/1). P.M.M. acknowledges generous support from Edmond J Safra Foundation and Lily Safra, the NIHR Senior Investigator programme and the UK Dementia Research Institute which receives its funding from DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK. P.M.M. and D.R.O. thank the Imperial College Healthcare Trust-NIHR Biomedical Research Centre for infrastructure support and the Medical Research Council for support of TSPO studies (MR/N016343/1). E.A. was supported by the ALS Stichting (grant “The Dutch ALS Tissue Bank”). P.M. and B.B.T. are funded by the Swiss National Science Foundation (projects 320030_184713 and 310030_212322, respectively). S.T. was supported by an “Early Postdoc.Mobility” scholarship (P2GEP3_191446) from the Swiss National Science Foundation, a “Clinical Medicine Plus” scholarship from the Prof Dr. Max Cloëtta Foundation (Zurich, Switzerland), from the Jean et Madeleine Vachoux Foundation (Geneva, Switzerland) and from the University Hospitals of Geneva. This work was funded by NIH grants U01AG061356 (De Jager/Bennett), RF1AG057473 (De Jager/Bennett), and U01AG046152 (De Jager/Bennett) as part of the AMP-AD consortium, as well as NIH grants R01AG066831 (Menon) and U01AG072572 (De Jager/St George-Hyslop)

    Mutations in TOP3A Cause a Bloom Syndrome-like Disorder

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    Bloom syndrome, caused by biallelic mutations in BLM, is characterized by prenatal-onset growth deficiency, short stature, an erythematous photosensitive malar rash, and increased cancer predisposition. Diagnostically, a hallmark feature is the presence of increased sister chromatid exchanges (SCEs) on cytogenetic testing. Here, we describe biallelic mutations in TOP3A in ten individuals with prenatal-onset growth restriction and microcephaly. TOP3A encodes topoisomerase III alpha (TopIIIα), which binds to BLM as part of the BTRR complex, and promotes dissolution of double Holliday junctions arising during homologous recombination. We also identify a homozygous truncating variant in RMI1, which encodes another component of the BTRR complex, in two individuals with microcephalic dwarfism. The TOP3A mutations substantially reduce cellular levels of TopIIIα, and consequently subjects’ cells demonstrate elevated rates of SCE. Unresolved DNA recombination and/or replication intermediates persist into mitosis, leading to chromosome segregation defects and genome instability that most likely explain the growth restriction seen in these subjects and in Bloom syndrome. Clinical features of mitochondrial dysfunction are evident in several individuals with biallelic TOP3A mutations, consistent with the recently reported additional function of TopIIIα in mitochondrial DNA decatenation. In summary, our findings establish TOP3A mutations as an additional cause of prenatal-onset short stature with increased cytogenetic SCEs and implicate the decatenation activity of the BTRR complex in their pathogenesis
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