Metabolic Cost of Supported Treadmill Running

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Genetic analysis of a major international collection of cultivated apple varieties reveals previously unknown historic heteroploid and inbred relationships

Domesticated apple (Malus x domestica Borkh.) is a major global crop and the genetic diversity held within the pool of cultivated varieties is important for the development of future cultivars. The aim of this study was to investigate the diversity held within the domesticated form, through the analysis of a major international germplasm collection of cultivated varieties, the UK National Fruit Collection, consisting of over 2,000 selections of named cultivars and seedling varieties. We utilised Diversity Array Technology (DArT) markers to assess the genetic diversity within the collection. Clustering attempts, using the software STRUCTURE revealed that the accessions formed a complex and historically admixed group for which clear clustering was challenging. Comparison of accessions using the Jaccard similarity coefficient allowed us to identify clonal and duplicate material as well as revealing pairs and groups that appeared more closely related than a standard parent-offspring or full-sibling relations. From further investigation, we were able to propose a number of new pedigrees, which revealed that some historically important cultivars were more closely related than previously documented and that some of them were partially inbred. We were also able to elucidate a number of parent-offspring relationships that had resulted in a number of important polyploid cultivars. This included reuniting polyploid cultivars that in some cases dated as far back as the 18th century, with diploid parents that potentially date back as far as the 13th century

Application of statistical and functional methodologies for the investigation of genetic determinants of coronary heart disease biomarkers: lipoprotein lipase genotype and plasma triglycerides as an exemplar

Genome-wide association studies have proved very successful in identifying novel single-nucleotide polymorphisms (SNPs) associated with disease or traits, but the related, functional SNP is usually unknown. In this paper, we describe a methodology to locate and validate candidate functional SNPs using lipoprotein lipase (LPL), a gene previously associated with triglyceride levels, as an exemplar. Two thousand seven hundred and eighty-six healthy middle-aged men from the NPHSII UK prospective study (with up to six measures of plasma lipid levels) were genotyped for 20 LPL tagging (t)SNPs using Illumina Bead technology. Using model-selection procedures and haplotypes, we identified eight SNPs that consistently maximized the fit of the model to the phenotype. Fifteen SNPs in high linkage disequilibrium with these were identified, and functional assays were carried out on all 23 SNPs. Electrophoretic mobility shift assay (EMSA) was used to identify SNPs that had the potential to alter DNA–protein interactions, reducing the number to eight possible candidate SNPs. These were examined for ability to alter expression using a luciferase reporter assay, and two regulatory SNPs, showing genotype differences, rs327 and rs3289, were identified. Finally, multiplexed-competitor-EMSA (MC-EMSA) and supershift EMSA identified FOXA2 to rs327T, and CREB-binding protein (CBP) and CCAAT displacement protein (CDP) to rs3289C as the factors responsible for transcription binding. We have identified two novel candidate functional SNPs in LPL and presented a procedure aimed to efficiently detect SNPs potentially causal to genetic association. We believe that this methodology could be successfully applied to future re-sequencing data

Metabolic Syndrome and Risk for Incident Alzheimer's Disease or Vascular Dementia: The Three-City Study

OBJECTIVE—Associations between metabolic syndrome and its individual components with risk of incident dementia and its different subtypes are inconsistent

Paired inspiratory-expiratory chest CT scans to assess for small airways disease in COPD

Abstract Background Gas trapping quantified on chest CT scans has been proposed as a surrogate for small airway disease in COPD. We sought to determine if measurements using paired inspiratory and expiratory CT scans may be better able to separate gas trapping due to emphysema from gas trapping due to small airway disease. Methods Smokers with and without COPD from the COPDGene Study underwent inspiratory and expiratory chest CT scans. Emphysema was quantified by the percent of lung with attenuation < −950HU on inspiratory CT. Four gas trapping measures were defined: (1) Exp−856, the percent of lung < −856HU on expiratory imaging; (2) E/I MLA, the ratio of expiratory to inspiratory mean lung attenuation; (3) RVC856-950, the difference between expiratory and inspiratory lung volumes with attenuation between −856 and −950 HU; and (4) Residuals from the regression of Exp−856 on percent emphysema. Results In 8517 subjects with complete data, Exp−856 was highly correlated with emphysema. The measures based on paired inspiratory and expiratory CT scans were less strongly correlated with emphysema. Exp−856, E/I MLA and RVC856-950 were predictive of spirometry, exercise capacity and quality of life in all subjects and in subjects without emphysema. In subjects with severe emphysema, E/I MLA and RVC856-950 showed the highest correlations with clinical variables. Conclusions Quantitative measures based on paired inspiratory and expiratory chest CT scans can be used as markers of small airway disease in smokers with and without COPD, but this will require that future studies acquire both inspiratory and expiratory CT scans.http://deepblue.lib.umich.edu/bitstream/2027.42/134586/1/12931_2012_Article_1346.pd

Measurement of the multi-TeV neutrino cross section with IceCube using Earth absorption

Neutrinos interact only very weakly, so they are extremely penetrating. However, the theoretical neutrino-nucleon interaction cross section rises with energy such that, at energies above 40 TeV, neutrinos are expected to be absorbed as they pass through the Earth. Experimentally, the cross section has been measured only at the relatively low energies (below 400 GeV) available at neutrino beams from accelerators \cite{Agashe:2014kda, Formaggio:2013kya}. Here we report the first measurement of neutrino absorption in the Earth, using a sample of 10,784 energetic upward-going neutrino-induced muons observed with the IceCube Neutrino Observatory. The flux of high-energy neutrinos transiting long paths through the Earth is attenuated compared to a reference sample that follows shorter trajectories through the Earth. Using a fit to the two-dimensional distribution of muon energy and zenith angle, we determine the cross section for neutrino energies between 6.3 TeV and 980 TeV, more than an order of magnitude higher in energy than previous measurements. The measured cross section is $1.30^{+0.21}_{-0.19}$ (stat.) $^{+0.39}_{-0.43}$ (syst.) times the prediction of the Standard Model \cite{CooperSarkar:2011pa}, consistent with the expectation for charged and neutral current interactions. We do not observe a dramatic increase in the cross section, expected in some speculative models, including those invoking new compact dimensions \cite{AlvarezMuniz:2002ga} or the production of leptoquarks \cite{Romero:2009vu}.Comment: Preprint version of Nature paper 10.1038/nature2445