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Sökning: WFRF:(Ward Jonathan)

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  • Elsik, Christine G., et al. (författare)
  • The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
  • 2009
  • Ingår i: Science. - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
  • Tidskriftsartikel (refereegranskat)abstract
    • To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
  • Schofield, James P. R., et al. (författare)
  • Stratification of asthma phenotypes by airway proteomic signatures
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - Elsevier. - 0091-6749 .- 1097-6825. ; 144:1, s. 70-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.
  • Ade, Peter, et al. (författare)
  • The Simons Observatory : science goals and forecasts
  • 2019
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - 1475-7516. ; :2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
  • Bancroft, Elizabeth K, et al. (författare)
  • Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study
  • 2014
  • Ingår i: European urology. - 1873-7560. ; 66:3, s. 489-499
  • Tidskriftsartikel (refereegranskat)abstract
    • Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations.
  • Burg, Dominic, et al. (författare)
  • Large-Scale Label-Free Quantitative Mapping of the Sputum Proteome
  • 2018
  • Ingår i: Journal of Proteome Research. - American Chemical Society (ACS). - 1535-3893. ; 17:6, s. 2072-2091
  • Tidskriftsartikel (refereegranskat)abstract
    • Analysis of induced sputum supematant is a minimally invasive approach to study the epithelial lining fluid and, thereby, provide insight into normal lung biology and the pathobiology of lung diseases. We present here a novel proteomics approach to sputum analysis developed within the U-BIOPRED (unbiased biomarkers predictive of respiratory disease outcomes) international project. We present practical and analytical techniques to optimize the detection of robust biomarkers in proteomic studies. The normal sputum proteome was derived using data-independent HDMSE applied to 40 healthy nonsmoking participants, which provides an essential baseline from which to compare modulation of protein expression in respiratory diseases. The "core" sputum proteome (proteins detected in >= 40% of participants) was composed of 284 proteins, and the extended proteome (proteins detected in >= 3 participants) contained 1666 proteins. Quality control procedures were developed to optimize the accuracy and consistency of measurement of sputum proteins and analyze the distribution of sputum proteins in the healthy population. The analysis showed that quantitation of proteins by HDMSE is influenced by several factors, with some proteins being measured in all participants' samples and with low measurement variance between samples from the same patient. The measurement of some proteins is highly variable between repeat analyses, susceptible to sample processing effects, or difficult to accurately quantify by mass spectrometry. Other proteins show high interindividual variance. We also highlight that the sputum proteome of healthy individuals is related to sputum neutrophil levels, but not gender or allergic sensitization. We illustrate the importance of design and interpretation of disease biomarker studies considering such protein population and technical measurement variance.
  • Connolly, J., et al. (författare)
  • Detecting recent disturbance on montane blanket bogs in the Wicklow Mountains, Ireland, using the MODIS enhanced vegetation index
  • 2011
  • Ingår i: International Journal of Remote Sensing. - Taylor & Francis. - 1366-5901. ; 32:9, s. 2377-2393
  • Tidskriftsartikel (refereegranskat)abstract
    • Irish peat soils are extensive, covering approximately 14-20% of the national land area. They contain between 53% and 62% of the national soil organic carbon stock. Montane blanket bog covers approximately 25% or 242650ha of the total peatland area in Ireland and is the dominant peatland type covering the upland area of Wicklow. Blanket bogs are very sensitive systems and have experienced much disturbance in Ireland due to overgrazing, burning, drainage, forestry and turf cutting. It has been estimated that disturbance of blanket bog, on a national area basis, ranges from 74% to 82% and in Wicklow is 57%. Disturbance can be detrimental to stocks of soil organic carbon in peatlands. Monitoring disturbance in peatlands, which tend to cover large, remote areas, is difficult and expensive using conventional surveying methods. Satellite remote sensing offers a way to gather data for these areas. In this paper a method of determining the probability of disturbance is presented. This method uses the Moderate Resolution Imaging Spectroradiometer (MODIS) Enhanced Vegetation Index (EVI) in combination with univariate image differencing along with thresholding and binary logistic regression. A probability map was produced depicting the geospatial patterns and pressures on the peatland soil organic carbon stock in Wicklow. Peat soils in higher and steeper areas were more disturbed and the primary disturbance in between 2000 and 2005 was fire. Lower, flatter areas did not experience as much disturbance probably because they are wetter. The consumer's and producer's accuracy for the map was 76% and 42%, respectively.
  • Connolly, John, et al. (författare)
  • Using MODIS derived fPAR with ground based flux tower measurements to derive the light use efficiency for two Canadian peatlands
  • 2009
  • Ingår i: Biogeosciences. - Copernicus Publications. - 1726-4189. ; 32:6, s. 225-225
  • Tidskriftsartikel (refereegranskat)abstract
    • We used satellite remote sensing data; fractionof photosynthetically active radiation absorbed by vegetation(fPAR) from the Moderate Resolution Imaging Spectrora-diometer (MODIS) in combination with tower eddy covari-ance and meteorological measurements to characterise theLight Use Efficiency parameter (ε)variability and the maxi-mumε(εmax)for two contrasting Canadian peatlands. Eight-day MODISfPAR data were acquired for the Mer Bleue(2000 to 2003) and Western Peatland (2004). Flux towereddy covariance and meteorological measurements were in-tegrated to the same eight-day time stamps as the MODISfPAR data. A light use efficiency model: GPP =ε×APAR(where GPP is Gross Primary Productivity and APAR is ab-sorbed photosynthetically active radiation) was used to cal-culateε. Theεmaxvalue for each year (2000 to 2003) at theMer Bleue bog ranged from 0.58 g C MJ−1to 0.78 g C MJ−1and was 0.91 g C MJ−1in 2004, for the Western Peatland.The average growing seasonεfor the Mer Bleue bog forthe four year period was 0.35 g C MJ−1and for the West-ern Peatland in 2004 was 0.57 g C MJ−1. The average snowfree period for the Mer Bleue bog over the four years was 0.27 g C MJ−1and for the Western Peatland in 2004 was0.39 g C MJ−1. Using the light use efficiency method wecalculated theεmaxand the annual variability inεfor twoCanadian peatlands. We determined that temperature was agrowth-limiting factor at both sites Vapour Pressure Deficit(VPD) however was not. MODISfPAR is a useful tool forthe characterization ofεat flux tower sites.
  • de Vries, Paul S., et al. (författare)
  • A genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology
  • 2019
  • Ingår i: Blood. - AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 133:9, s. 967-977
  • Tidskriftsartikel (refereegranskat)abstract
    • Factor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of 9 genome-wide association studies of plasma FVII levels (7 FVII activity and 2 FVII antigen) among 27 495 participants of European and African ancestry. Each study performed ancestry-specific association analyses. Inverse variance weighted meta-analysis was performed within each ancestry group and then combined for a trans-ancestry meta-analysis. Our primary analysis included the 7 studies that measured FVII activity, and a secondary analysis included all 9 studies. We provided functional genomic validation for newly identified significant loci by silencing candidate genes in a human liver cell line (HuH7) using small-interfering RNA and then measuring F7 messenger RNA and FVII protein expression. Lastly, we used meta-analysis results to perform Mendelian randomization analysis to estimate the causal effect of FVII activity on coronary artery disease, ischemic stroke (IS), and venous thromboembolism. We identified 2 novel (REEP3 and JAZF1-AS1) and 6 known loci associated with FVII activity, explaining 19.0% of the phenotypic variance. Adding FVII antigen data to the meta-analysis did not result in the discovery of further loci. Silencing REEP3 in HuH7 cells upregulated FVII, whereas silencing JAZF1 downregulated FVII. Mendelian randomization analyses suggest that FVII activity has a positive causal effect on the risk of IS. Variants at REEP3 and JAZF1 contribute to FVII activity by regulating F7 expression levels. FVII activity appears to contribute to the etiology of IS in the general population.
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