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Träfflista för sökning "WFRF:(Anderson Kevin) srt2:(2010-2014)"

Sökning: WFRF:(Anderson Kevin) > (2010-2014)

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1.
  • Randall, Joshua C., et al. (författare)
  • Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits
  • 2013
  • Ingår i: PLoS Genetics. - : Public Library of Science. - 1553-7404 .- 1553-7390. ; 9:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5x10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
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2.
  • Haq, Rizwan, et al. (författare)
  • BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition
  • 2013
  • Ingår i: Proceedings of the National Academy of Sciences. - : National Acad Sciences. - 1091-6490. ; 110:11, s. 4321-4326
  • Tidskriftsartikel (refereegranskat)abstract
    • Although targeting oncogenic mutations in the BRAF serine/threonine kinase with small molecule inhibitors can lead to significant clinical responses in melanoma, it fails to eradicate tumors in nearly all patients. Successful therapy will be aided by identification of intrinsic mechanisms that protect tumor cells from death. Here, we used a bioinformatics approach to identify drug-able, "driver" oncogenes restricted to tumor versus normal tissues. Applying this method to 88 short-term melanoma cell cultures, we show that the antiapoptotic BCL2 family member BCL2A1 is recurrently amplified in similar to 30% of melanomas and is necessary for melanoma growth. BCL2A1 overexpression also promotes melanomagenesis of BRAF-immortalized melanocytes. We find that high-level expression of BCL2A1 is restricted to melanoma due to direct transcriptional control by the melanoma oncogene MITF. Although BRAF inhibitors lead to cell cycle arrest and modest apoptosis, we find that apoptosis is significantly enhanced by suppression of BCL2A1 in melanomas with BCL2A1 or MITF amplification. Moreover, we find that BCL2A1 expression is associated with poorer clinical responses to BRAF pathway inhibitors in melanoma patients. Cotreatment of melanomas with BRAF inhibitors and obatoclax, an inhibitor of BCL2A1 and other BCL2 family members, overcomes intrinsic resistance to BRAF inhibitors in BCL2A1-amplified cells in vitro and in vivo. These studies identify MITF-BCL2A1 as a lineage-specific oncogenic pathway in melanoma and underscore its role for improved response to BRAF-directed therapy.
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3.
  • Wood, Andrew R, et al. (författare)
  • Defining the role of common variation in the genomic and biological architecture of adult human height.
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 46:11, s. 1173-1186
  • Tidskriftsartikel (refereegranskat)abstract
    • Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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4.
  • Bentley, Michael J., et al. (författare)
  • A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum
  • 2014
  • Ingår i: Quaternary Science Reviews. - : Elsevier. - 0277-3791 .- 1873-457X. ; 100, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20 ka, 15 ka, 10 ka and 5 ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse la. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorities for future work. The synthesis is intended to be a resource for the modelling and glacial geological community. (C) 2014 The Authors. Published by Elsevier Ltd.
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5.
  • Denver, Dee R, et al. (författare)
  • Selective sweeps and parallel mutation in the adaptive recovery from deleterious mutation in Caenorhabditis elegans.
  • 2010
  • Ingår i: Genome Research. - 1088-9051 .- 1549-5469. ; 20:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Deleterious mutation poses a serious threat to human health and the persistence of small populations. Although adaptive recovery from deleterious mutation has been well-characterized in prokaryotes, the evolutionary mechanisms by which multicellular eukaryotes recover from deleterious mutation remain unknown. We applied high-throughput DNA sequencing to characterize genomic divergence patterns associated with the adaptive recovery from deleterious mutation using a Caenorhabditis elegans recovery-line system. The C. elegans recovery lines were initiated from a low-fitness mutation-accumulation (MA) line progenitor and allowed to independently evolve in large populations (N ∼ 1000) for 60 generations. All lines rapidly regained levels of fitness similar to the wild-type (N2) MA line progenitor. Although there was a near-zero probability of a single mutation fixing due to genetic drift during the recovery experiment, we observed 28 fixed mutations. Cross-generational analysis showed that all mutations went from undetectable population-level frequencies to a fixed state in 10-20 generations. Many recovery-line mutations fixed at identical timepoints, suggesting that the mutations, if not beneficial, hitchhiked to fixation during selective sweep events observed in the recovery lines. No MA line mutation reversions were detected. Parallel mutation fixation was observed for two sites in two independent recovery lines. Analysis using a C. elegans interactome map revealed many predicted interactions between genes with recovery line-specific mutations and genes with previously accumulated MA line mutations. Our study suggests that recovery-line mutations identified in both coding and noncoding genomic regions might have beneficial effects associated with compensatory epistatic interactions.
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6.
  • Howard, Andrew W., et al. (författare)
  • The California planet survey. I. four new giant exoplanets
  • 2010
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 721:2, s. 1467-1481
  • Tidskriftsartikel (refereegranskat)abstract
    • We present precise Doppler measurements of four stars obtained during the past decade at Keck Observatory by the California Planet Survey (CPS). These stars, namely, HD 34445, HD 126614, HD 13931, and Gl 179, all show evidence for a single planet in Keplerian motion. We also present Doppler measurements from the Hobby-Eberly Telescope (HET) for two of the stars, HD 34445 and Gl 179, that confirm the Keck detections and significantly refine the orbital parameters. These planets add to the statistical properties of giant planets orbiting near or beyond the ice line, and merit follow-up by astrometry, imaging, and space-borne spectroscopy. Their orbital parameters span wide ranges of planetary minimum mass (M sin i = 0.38-1.9 M-Jup), orbital period (P = 2.87-11.5 yr), semimajor axis (a = 2.1-5.2 AU), and eccentricity (e = 0.02-0.41). HD 34445 b (P = 2.87 yr, M sin i = 0.79 MJup, e = 0.27) is a massive planet orbiting an old, G-type star. We announce a planet, HD 126614 Ab, and an M dwarf, HD 126614 B, orbiting the metal-rich star HD 126614 (which we now refer to as HD 126614 A). The planet, HD 126614 Ab, has minimum mass M sin i = 0.38 MJup and orbits the stellar primary with period P = 3.41 yr and orbital separation a = 2.3 AU. The faint M dwarf companion, HD 126614 B, is separated from the stellar primary by 489 mas (33 AU) and was discovered with direct observations using adaptive optics and the PHARO camera at Palomar Observatory. The stellar primary in this new system, HD 126614 A, has the highest measured metallicity ([ Fe/ H] = + 0.56) of any known planet-bearing star. HD 13931 b (P = 11.5 yr, M sin i = 1.88 MJup, e = 0.02) is a Jupiter analog orbiting a near solar twin. Gl 179 b (P = 6.3 yr, M sin i = 0.82 M-Jup, e = 0.21) is a massive planet orbiting a faint M dwarf. The high metallicity of Gl 179 is consistent with the planet-metallicity correlation among M dwarfs, as documented recently by Johnson & Apps.
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7.
  • Hunsicker, Mary E., et al. (författare)
  • Functional responses and scaling in predator-prey interactions of marine fishes : contemporary issues and emerging concepts
  • 2011
  • Ingår i: Ecology Letters. - : Wiley-Blackwell. - 1461-023X .- 1461-0248. ; 14:12, s. 1288-1299
  • Forskningsöversikt (refereegranskat)abstract
    • Predatorprey interactions are a primary structuring force vital to the resilience of marine communities and sustainability of the worlds oceans. Human influences on marine ecosystems mediate changes in species interactions. This generality is evinced by the cascading effects of overharvesting top predators on the structure and function of marine ecosystems. It follows that ecological forecasting, ecosystem management, and marine spatial planning require a better understanding of food web relationships. Characterising and scaling predatorprey interactions for use in tactical and strategic tools (i.e. multi-species management and ecosystem models) are paramount in this effort. Here, we explore what issues are involved and must be considered to advance the use of predatorprey theory in the context of marine fisheries science. We address pertinent contemporary ecological issues including (1) the approaches and complexities of evaluating predator responses in marine systems; (2) the scaling up of predatorprey interactions to the population, community, and ecosystem level; (3) the role of predatorprey theory in contemporary fisheries and ecosystem modelling approaches; and (4) directions for the future. Our intent is to point out needed research directions that will improve our understanding of predatorprey interactions in the context of the sustainable marine fisheries and ecosystem management.
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8.
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9.
  • Milisavljevic, Dan, et al. (författare)
  • MULTI-WAVELENGTH OBSERVATIONS OF SUPERNOVA 2011ei : TIME-DEPENDENT CLASSIFICATION OF TYPE IIb AND Ib SUPERNOVAE AND IMPLICATIONS FOR THEIR PROGENITORS
  • 2013
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 767:1, s. 71-
  • Tidskriftsartikel (refereegranskat)abstract
    • We present X-ray, UV/optical, and radio observations of the stripped-envelope, core-collapse supernova (SN) 2011ei, one of the least luminous SNe IIb or Ib observed to date. Our observations begin with a discovery within similar to 1 day of explosion and span several months afterward. Early optical spectra exhibit broad, Type II-like hydrogen Balmer profiles that subside rapidly and are replaced by Type Ib-like He-rich features on a timescale of one week. High-cadence monitoring of this transition suggests absorption attributable to a high-velocity (greater than or similar to 12,000 km s(-1)) H-rich shell, which is likely present in many Type Ib events. Radio observations imply a shock velocity of v approximate to 0.13 c and a progenitor star average mass-loss rate of (M) over dot approximate to 1.4 x 10(-5) M-circle dot yr(-1) (assuming wind velocity v(w) = 10(3) km s(-1)). This is consistent with independent constraints from deep X-ray observations with Swift-XRT and Chandra. Overall, the multi-wavelength properties of SN 2011ei are consistent with the explosion of a lower-mass (3-4 M-circle dot), compact (R-* less than or similar to 1 x 10(11) cm), He-core star. The star retained a thin hydrogen envelope at the time of explosion, and was embedded in an inhomogeneous circumstellar wind suggestive of modest episodic mass loss. We conclude that SN 2011ei's rapid spectral metamorphosis is indicative of time-dependent classifications that bias estimates of the relative explosion rates for Type IIb and Ib objects, and that important information about a progenitor star's evolutionary state and mass loss immediately prior to SN explosion can be inferred from timely multi-wavelength observations.
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10.
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