625 research outputs found

    Deletion of Panx3 Prevents the Development of Surgically Induced Osteoarthritis

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    © 2015, Springer-Verlag Berlin Heidelberg. Abstract: Osteoarthritis (OA) is a highly prevalent, disabling joint disease with no existing therapies to slow or halt its progression. Cartilage degeneration hallmarks OA pathogenesis, and pannexin 3 (Panx3), a member of a novel family of channel proteins, is upregulated during this process. The function of Panx3 remains poorly understood, but we consistently observed a strong increase in Panx3 immunostaining in OA lesions in both mice and humans. Here, we developed and characterized the first global and conditional Panx3 knockout mice to investigate the role of Panx3 in OA. Interestingly, global Panx3 deletion produced no overt phenotype and had no obvious effect on early skeletal development. Mice lacking Panx3 specifically in the cartilage and global Panx3 knockout mice were markedly resistant to the development of OA following destabilization of medial meniscus surgery. These data indicate a specific catabolic role of Panx3 in articular cartilage and identify Panx3 as a potential therapeutic target for OA. Lastly, while Panx1 has been linked to over a dozen human pathologies, this is the first in vivo evidence for a role of Panx3 in disease. Key message: Panx3 is localized to cartilage lesions in mice and humans.Global Panx3 deletion does not result in any developmental abnormalities.Mice lacking Panx3 are resistant to the development of osteoarthritis.Panx3 is a novel therapeutic target for the treatment of osteoarthritis

    Training of Instrumentalists and Development of New Technologies on SOFIA

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    This white paper is submitted to the Astronomy and Astrophysics 2010 Decadal Survey (Astro2010)1 Committee on the State of the Profession to emphasize the potential of the Stratospheric Observatory for Infrared Astronomy (SOFIA) to contribute to the training of instrumentalists and observers, and to related technology developments. This potential goes beyond the primary mission of SOFIA, which is to carry out unique, high priority astronomical research. SOFIA is a Boeing 747SP aircraft with a 2.5 meter telescope. It will enable astronomical observations anywhere, any time, and at most wavelengths between 0.3 microns and 1.6 mm not accessible from ground-based observatories. These attributes, accruing from the mobility and flight altitude of SOFIA, guarantee a wealth of scientific return. Its instrument teams (nine in the first generation) and guest investigators will do suborbital astronomy in a shirt-sleeve environment. The project will invest $10M per year in science instrument development over a lifetime of 20 years. This, frequent flight opportunities, and operation that enables rapid changes of science instruments and hands-on in-flight access to the instruments, assure a unique and extensive potential - both for training young instrumentalists and for encouraging and deploying nascent technologies. Novel instruments covering optical, infrared, and submillimeter bands can be developed for and tested on SOFIA by their developers (including apprentices) for their own observations and for those of guest observers, to validate technologies and maximize observational effectiveness.Comment: 10 pages, no figures, White Paper for Astro 2010 Survey Committee on State of the Professio

    The correlation between reading and mathematics ability at age twelve has a substantial genetic component

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    Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve

    Combining steady state and temperature jump IR spectroscopy to investigate the allosteric effects of ligand binding to dsDNA

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    Changes in the structural dynamics of double stranded (ds)DNA upon ligand binding have been linked to the mechanism of allostery without conformational change, but direct experimental evidence remains elusive. To address this, a combination of steady state infrared (IR) absorption spectroscopy and ultrafast temperature jump IR absorption measurements has been used to quantify the extent of fast (∼100 ns) fluctuations in (ds)DNA·Hoechst 33258 complexes at a range of temperatures. Exploiting the direct link between vibrational band intensities and base stacking shows that the absolute magnitude of the change in absorbance caused by fast structural fluctuations following the temperature jump is only weakly dependent on the starting temperature of the sample. The observed fast dynamics are some two orders of magnitude faster than strand separation and associated with all points along the 10-base pair duplex d(GCATATATCC). Binding the Hoechst 33258 ligand causes a small but consistent reduction in the extent of these fast fluctuations of base pairs located outside of the ligand binding region. These observations point to a ligand-induced reduction in the flexibility of the dsDNA near the binding site, consistent with an estimated allosteric propagation length of 15 Å, about 5 base pairs, which agrees well with both molecular simulation and coarse-grained statistical mechanics models of allostery leading to cooperative ligand binding

    Electrical, morphological and structural properties of RF magnetron sputtered Mo thin films for application in thin film photovoltaic solar cells

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    Molybdenum (Mo) thin films were deposited using radio frequency magnetron sputtering, for application as a metal back contact material in ‘‘substrate configuration’’ thin film solar cells. The variations of the electrical, morphological, and structural properties of the deposited films with sputtering pressure, sputtering power and post-deposition annealing were determined. The electrical conductivity of the Mo films was found to increase with decreasing sputtering pressure and increasing sputtering power. X-ray diffraction data showed that all the films had a (110) preferred orientation that became less pronounced at higher sputtering power while being relatively insensitive to process pressure. The lattice stress within the films changed from tensile to compressive with increasing sputtering power and the tensile stress increased with increasing sputtering pressure. The surface morphology of the films changed from pyramids to cigar-shaped grains for a sputtering power between 100 and 200 W, remaining largely unchanged at higher power. These grains were also observed to decrease in size with increasing sputtering pressure. Annealing the films was found to affect the resistivity and stress of the films. The resistivity increased due to the presence of residual oxygen and the stress changed from tensile to compressive. The annealing step was not found to affect the crystallisation and grain growth of the Mo films

    Multivariate Genetic analysis of Personality and Cognitive Traits Reveals abundant Pleiotropy

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    Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the \u27pleiotropy-informed\u27 multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies of the Big 5 personality traits and cognitive function on our multivariate findings, boosting genetic discovery in other personality traits and improving polygenic prediction. These findings advance our understanding of the polygenic architecture of these complex mental traits, indicating a prominence of pleiotropic genetic effects across higher order domains of mental function such as personality and cognitive function
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