2,876 research outputs found

    Striatal neuroinflammation promotes parkinsonism in rats

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    The specific role of neuroinflammation in the pathogenesis of Parkinson's disease remains to be fully elucidated. By infusing lipopolysaccharide (LPS) into the striatum, we investigated the effect of neuroinflammation on the dopamine nigrostriatal pathway. Here, we report that LPS-induced neuroinflammation in the striatum causes progressive degeneration of the dopamine nigrostriatal system, which is accompanied by motor impairments resembling parkinsonism. Our results indicate that neurodegeneration is associated with defects in the mitochondrial respiratory chain related to extensive S-nitrosylation/nitration of mitochondrial proteins. Mitochondrial injury was prevented by treatment of L-N^6^-(l-iminoethyl)-lysine, an inducible nitric oxide synthase (iNOS) inhibitor, suggesting that iNOS-derived NO is responsible for mitochondrial dysfunction. Furthermore, the nigral dopamine neurons exhibited intracytoplasmic [alpha]-synuclein and ubiquitin accumulation. These results demonstrate that degeneration of nigral dopamine neurons by neuroinflammation is associated with mitochondrial malfunction induced by NO-mediated S-nitrosylation/nitration of mitochondrial proteins

    Challenging homophobic bullying in schools: the politics of progress

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    In recent years homophobic bullying has received increased attention from NGOs, academics and government sources and concern about the issue crosses traditional moral and political divisions. This article examines this ‘progressive’ development and identifies the ‘conditions of possibility’ that have enabled the issue to become a harm that can be spoken of. In doing so it questions whether the readiness to speak about the issue represents the opposite to prohibitions on speech (such as the notorious Section 28) or whether it is based on more subtle forms of governance. It argues that homophobic bullying is heard through three key discourses (‘child abuse’, ‘the child victim’ and ‘the tragic gay’) and that, while enabling an acknowledgement of certain harms, they simultaneously silence other needs and experiences. It then moves to explore the aspirational and ‘liberatory’ political investments that underlie these seemingly ‘common-sense’ descriptive discourses and concludes with a critique of the quasi-criminal responses that the dominant political agenda of homophobic bullying gives rise to. The article draws on, and endeavours to develop a conversation between, critical engagements with the contemporary politics of both childhood and sexuality

    Engineering Analysis Studies for Preliminary Design of Lightweight Cryogenic Hydrogen Tanks in UAV Applications

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    A series of engineering analysis studies were conducted to investigate the potential application of nanoclay-enhanced graphite/epoxy composites and polymer cross-linked silica aerogels in cryogenic hydrogen storage tank designs. This assessment focused on the application of these materials in spherical tank designs for unmanned aeronautic vehicles with mission durations of 14 days. Two cryogenic hydrogen tank design concepts were considered: a vacuum-jacketed design and a sandwiched construction with an aerogel insulating core. Analyses included thermal and structural analyses of the tank designs as well as an analysis of hydrogen diffusion to specify the material permeability requirements. The analyses also provided material property targets for the continued development of cross-linked aerogels and nanoclay-enhanced graphite/epoxy composites for cryogenic storage tank applications. The results reveal that a sandwiched construction with an aerogel core is not a viable design solution for a 14-day mission. A vacuum-jacketed design approach was shown to be far superior to an aerogel. Aerogel insulation may be feasible for shorter duration missions. The results also reveal that the application of nanoclay-enhanced graphite/epoxy should be limited to the construction of outer tanks in a vacuum-jacketed design, since a graphite/epoxy inner tank does not provide a significant weight savings over aluminum and since the ability of nanoclay-enhanced graphite/epoxy to limit hydrogen permeation is still in question

    The Upper Respiratory Tract as a Microbial Source for Pulmonary Infections in Cystic Fibrosis. Parallels from Island Biogeography

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    A continuously mixed series of microbial communities inhabits various points of the respiratory tract, with community composition determined by distance from colonization sources, colonization rates, and extinction rates. Ecology and evolution theory developed in the context of biogeography is relevant to clinical microbiology and could reframe the interpretation of recent studies comparing communities from lung explant samples, sputum samples, and oropharyngeal swabs. We propose an island biogeography model of the microbial communities inhabiting different niches in human airways. Island biogeography as applied to communities separated by time and space is a useful parallel for exploring microbial colonization of healthy and diseased lungs, with the potential to inform our understanding of microbial community dynamics and the relevance of microbes detected in different sample types. In this perspective, we focus on the intermixed microbial communities inhabiting different regions of the airways of patients with cystic fibrosis

    Child maltreatment in the "children of the nineties" : a cohort study of risk factors

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    Aim: To analyze the multiple factors affecting the risk of maltreatment in young children within a comprehensive theoretical framework. Methods: The research is based on a large UK cohort study, the Avon Longitudinal Study of Parents and Children. Out of 14,256 children participating in the study, 293 were investigated by social services for suspected maltreatment and 115 were placed on local child protection registers prior to their 6th birthday. Data on the children have been obtained from obstetric data and from a series of parental questionnaires administered during pregnancy and the first 3 years of life. Risk factors have been analyzed using an hierarchical approach to logistic regression analysis. Results: In the stepwise hierarchical analysis, young parents, those with low educational achievement, and those with a past psychiatric history or a history of childhood abuse were all more likely to be investigated for maltreatment, or to have a child placed on the child protection register, with odds ratios between 1.86 and 4.96 for registration. Examining strength of effect, the highest risks were found with indicators of deprivation (3.24 for investigation and 11.02 for registration, after adjusting for parental background factors). Poor social networks increased the risk of both investigation (adjusted OR 1.93) and registration (adjusted OR 1.90). Maternal employment seemed to reduce the risk of both outcomes but adjusted odds ratios were no longer significant for registration. After adjusting for higher order confounders, single parents and reordered families were both at higher risk of registration. Reported domestic violence increased the risk of investigation and registration but this was no longer significant after adjusting for higher order variables. Low birthweight children were at higher risk of registration as were those whose parents reported few positive attributes of their babies. Conclusions: This study supports previous research in the field demonstrating that a wide range of factors in the parental background, socio-economic and family environments affect the risk of child maltreatment. By combining factors within a comprehensive ecological framework, we have demonstrated that the strongest risks are from socio-economic deprivation and from factors in the parents' own background and that parental background factors are largely, but not entirely, mediated through their impact on socio-economic factors

    A Further Look at Potential Impact of Satlets on Design, Production, and Cost of Satellite Systems

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    For the past 50 years, the morphology for satellites has remained fundamentally unchanged despite evolutions in manufacturing, communications, and software occurring in other industries. Primary spacecraft support systems—power, attitude control, and others—are designed in the same way, whether in space telescopes, large communications satellites, interplanetary spacecraft, or Cubesats. This paradigm has been the status quo in spacecraft design and construction and has precluded any industry-wide, large-scale cost savings while maintaining performance. To change this trend and ensure performance and utility at low cost, that can scale, DARPA postulated the concept of a cellularized satellite, or “satlet,” as a satellite architectural unit. In this new morphology, each satlet would provide some fraction of the overall functions that, when aggregated via hardware and software, provide spacecraft space system with its complete required capabilities. The DARPA Phoenix program has developed this satlet morphology in Phase I and plans to validate and demonstrate it in a series of steps that exercise various applications and levels of configuration flexibility enabled by a satlet architecture. The first system experiment is planned to be conducted on orbit in 2015. This paper aims to take a deeper look at the potential impact of space systems with cellular based designs, and using historical data showcases how design, production and ultimately cost can form the foundation for next generation spacecraft opportunities. A first order analysis conducted in a previous paper indicated that U.S.-launched satellites alone could create a market demand for 2,000-8,000 satlets flown per year, while the overall annual world satellite market could create demand for 10,000-40,000 satlets. This paper explores the instantiation of a cellular morphology to design, production and development to further quantify the impact of this revolutionary space system capability

    Genomes of marine cyanopodoviruses reveal multiple origins of diversity

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    The marine cyanobacteria Prochlorococcus and Synechococcus are highly abundant in the global oceans, as are the cyanophage with which they co-evolve. While genomic analyses have been relatively extensive for cyanomyoviruses, only three cyanopodoviruses isolated on marine cyanobacteria have been sequenced. Here we present nine new cyanopodovirus genomes, and analyse them in the context of the broader group. The genomes range from 42.2 to 47.7 kb, with G+C contents consistent with those of their hosts. They share 12 core genes, and the pan-genome is not close to being fully sampled. The genomes contain three variable island regions, with the most hypervariable genes concentrated at one end of the genome. Concatenated core-gene phylogeny clusters all but one of the phage into three distinct groups (MPP-A and two discrete clades within MPP-B). The outlier, P-RSP2, has the smallest genome and lacks RNA polymerase, a hallmark of the Autographivirinae subfamily. The phage in group MPP-B contain photosynthesis and carbon metabolism associated genes, while group MPP-A and the outlier P-RSP2 do not, suggesting different constraints on their lytic cycles. Four of the phage encode integrases and three have a host integration signature. Metagenomic analyses reveal that cyanopodoviruses may be more abundant in the oceans than previously thought.National Science Foundation (U.S.). Center for Microbial Oceanography: Research and Education (Grant OCE-042560)National Science Foundation (U.S.). Center for Microbial Oceanography: Research and Education (Grant EF 0424599
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