3,608 research outputs found

    Mutant glycyl-tRNA synthetase (Gars) ameliorates SOD1G93A motor neuron degeneration phenotype but has little affect on Loa dynein heavy chain mutant mice

    Get PDF
    Background: In humans, mutations in the enzyme glycyl-tRNA synthetase (GARS) cause motor and sensory axon loss in the peripheral nervous system, and clinical phenotypes ranging from Charcot-Marie-Tooth neuropathy to a severe infantile form of spinal muscular atrophy. GARS is ubiquitously expressed and may have functions in addition to its canonical role in protein synthesis through catalyzing the addition of glycine to cognate tRNAs. Methodology/Principal findings: We have recently described a new mouse model with a point mutation in the Gars gene resulting in a cysteine to arginine change at residue 201. Heterozygous Gars^{C201R/+} mice have locomotor and sensory deficits. In an investigation of genetic mutations that lead to death of motor and sensory neurons, we have crossed the Gars^{C201R/+} mice to two other mutants: the TgSOD1^{G93A} model of human amyotrophic lateral sclerosis and the Legs at odd angles mouse (Dync1h1^{Loa}) which has a defect in the heavy chain of the dynein complex. We found the Dync1h1^{Loa/+}; Gars^{C201R/+} double heterozygous mice are more impaired than either parent, and this is may be an additive effect of both mutations. Surprisingly, the Gars^{C201R} mutation significantly delayed disease onset in the SOD1^{G93A}; Gars^{C201R/+} double heterozygous mutant mice and increased lifespan by 29% on the genetic background investigated. Conclusions/Significance: These findings raise intriguing possibilities for the study of pathogenetic mechanisms in all three mouse mutant strains

    A Transiting Jupiter Analog

    Get PDF
    Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of (0.91±0.02)(0.91\pm0.02) RJupR_{\mathrm{Jup}}, a low orbital eccentricity (0.060.04+0.100.06_{-0.04}^{+0.10}) and an equilibrium temperature of (131±3)(131\pm3) K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric coverage, we are able to uniquely and precisely measure the orbital period of this post snow-line planet (1071.2323±0.00061071.2323\pm0.0006 d), paving the way for follow-up of this K=11.8K=11.8 mag target.Comment: 14 pages, 10 figures. Accepted to ApJ. Posteriors available at https://github.com/CoolWorlds/Kepler-167-Posterior

    Protein annotation and modelling servers at University College London

    Get PDF
    The UCL Bioinformatics Group web portal offers several high quality protein structure prediction and function annotation algorithms including PSIPRED, pGenTHREADER, pDomTHREADER, MEMSAT, MetSite, DISOPRED2, DomPred and FFPred for the prediction of secondary structure, protein fold, protein structural domain, transmembrane helix topology, metal binding sites, regions of protein disorder, protein domain boundaries and protein function, respectively. We also now offer a fully automated 3D modelling pipeline: BioSerf, which performed well in CASP8 and uses a fragment-assembly approach which placed it in the top five servers in the de novo modelling category. The servers are available via the group web site at http://bioinf.cs.ucl.ac.uk/

    The Kepler End-to-End Model: Creating High-Fidelity Simulations to Test Kepler Ground Processing

    Get PDF
    The Kepler mission is designed to detect the transit of Earth-like planets around Sun-like stars by observing 100,000 stellar targets. Developing and testing the Kepler ground-segment processing system, in particular the data analysis pipeline, requires high-fidelity simulated data. This simulated data is provided by the Kepler End-to-End Model (ETEM). ETEM simulates the astrophysics of planetary transits and other phenomena, properties of the Kepler spacecraft and the format of the downlinked data. Major challenges addressed by ETEM include the rapid production of large amounts of simulated data, extensibility and maintainability

    Negotiation in strategy making teams : group support systems and the process of cognitive change

    Get PDF
    This paper reports on the use of a Group Support System (GSS) to explore at a micro level some of the processes manifested when a group is negotiating strategy-processes of social and psychological negotiation. It is based on data from a series of interventions with senior management teams of three operating companies comprising a multi-national organization, and with a joint meeting subsequently involving all of the previous participants. The meetings were concerned with negotiating a new strategy for the global organization. The research involved the analysis of detailed time series data logs that exist as a result of using a GSS that is a reflection of cognitive theory

    Asteroseismology of the solar analogs 16 Cyg A & B from Kepler observations

    Get PDF
    The evolved solar-type stars 16 Cyg A & B have long been studied as solar analogs, yielding a glimpse into the future of our own Sun. The orbital period of the binary system is too long to provide meaningful dynamical constraints on the stellar properties, but asteroseismology can help because the stars are among the brightest in the Kepler field. We present an analysis of three months of nearly uninterrupted photometry of 16 Cyg A & B from the Kepler space telescope. We extract a total of 46 and 41 oscillation frequencies for the two components respectively, including a clear detection of octupole (l=3) modes in both stars. We derive the properties of each star independently using the Asteroseismic Modeling Portal, fitting the individual oscillation frequencies and other observational constraints simultaneously. We evaluate the systematic uncertainties from an ensemble of results generated by a variety of stellar evolution codes and fitting methods. The optimal models derived by fitting each component individually yield a common age (t=6.8+/-0.4 Gyr) and initial composition (Z_i=0.024+/-0.002, Y_i=0.25+/-0.01) within the uncertainties, as expected for the components of a binary system, bolstering our confidence in the reliability of asteroseismic techniques. The longer data sets that will ultimately become available will allow future studies of differential rotation, convection zone depths, and long-term changes due to stellar activity cycles.Comment: 6 pages, 2 figures, 2 tables, ApJ Letters (accepted
    corecore