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Träfflista för sökning "WFRF:(Evans P. A.) "

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  • Lindbladh, C, et al. (författare)
  • Preparation and kinetic characterization of a fusion protein of yeast mitochondrial citrate synthase and malate dehydrogenase
  • 1994
  • Ingår i: Biochemistry. - : The American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 33:39, s. 8-11692
  • Tidskriftsartikel (refereegranskat)abstract
    • We have expressed the DNA of the fusion of CS1 to MDH1 in Escherichia coli gltA-. The fusion protein (CS1/MDH1) is the C-terminus of CS1 linked in-frame to the N-terminus of MDH1 with a short linker of glycyl-seryl-glycyl. The fusion protein produced was isolated and purified. Gel filtration studies indicated that CS1/MDH1 had a M(r) of approximately 170,000. Western blotting analysis with SDS gel indicated a M(r) of approximately 90,000-95,000 (theoretical M(r) = 87,000). This is the expected M(r) for the fusion protein subunit. The kinetics of CS1 and MDH1 activities of the fusion protein were compared to those of the free enzymes. In addition, the effect of AAT reaction, as a competitor for the intermediate OAA of the coupled MDH-CS reaction, was examined. It was observed that AAT was a less effective competitor for OAA when the CS1/MDH1 fusion protein is used than when the separate enzymes are employed. In addition, the transient time for the coupled reaction sequence was less for the fusion protein than for the free enzymes.
  • Loos, Ruth J. F., et al. (författare)
  • Common variants near MC4R are associated with fat mass, weight and risk of obesity
  • 2008
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 40:6, s. 768-775
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.
  • Lüpold, Stefan, et al. (författare)
  • How sperm competition shapes the evolution of testes and sperm : a meta-analysis
  • 2020
  • Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1813
  • Tidskriftsartikel (refereegranskat)abstract
    • Females of many species mate with multiple males, thereby inciting competition among ejaculates from rival males for fertilization. In response to increasing sperm competition, males are predicted to enhance their investment in sperm production. This prediction is so widespread that testes size (correcting for body size) is commonly used as a proxy of sperm competition, even in the absence of any other information about a species' reproductive behaviour. By contrast, a debate about whether sperm competition selects for smaller or larger sperm has persisted for nearly three decades, with empirical studies demonstrating every possible response. Here, we synthesize nearly 40 years of sperm competition research in a meta-analytical framework to determine how the evolution of sperm number (i.e. testes size) and sperm size (i.e. sperm head, midpiece, flagellum and total length) is influenced by varying levels of sperm competition across species. Our findings support the long-held assumption that higher levels of sperm competition are associated with relatively larger testes. We also find clear evidence that sperm competition is associated with increases in all components of sperm length. We discuss these results in the context of different theoretical predictions and general patterns in the breeding biology and selective environment of sperm. This article is part of the theme issue 'Fifty years of sperm competition'.
  • McGinn, Steven, et al. (författare)
  • New Technologies for DNA analysis-A review of the READNA Project.
  • 2016
  • Ingår i: New Biotechnology. - : Elsevier. - 1876-4347 .- 1871-6784.
  • Forskningsöversikt (refereegranskat)abstract
    • The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received funding from the European Commission for 4 1/2 years. The objectives of the project revolved around technological developments in nucleic acid analysis. The project partners have discovered, created and developed a huge body of insights into nucleic acid analysis, ranging from improvements and implementation of current technologies to the most promising sequencing technologies that constitute a 3(rd) and 4(th) generation of sequencing methods with nanopores and in situ sequencing, respectively.
  • McGregor, Helen V., et al. (författare)
  • Robust global ocean cooling trend for the pre-industrial Common Era
  • 2015
  • Ingår i: Nature Geoscience. - : Nature Publishing Group. - 1752-0908. ; 8:9, s. 671-677
  • Tidskriftsartikel (refereegranskat)abstract
    • The oceans mediate the response of global climate to natural and anthropogenic forcings. Yet for the past 2,000 years - a key interval for understanding the present and future climate response to these forcings - global sea surface temperature changes and the underlying driving mechanisms are poorly constrained. Here we present a global synthesis of sea surface temperatures for the Common Era (CE) derived from 57 individual marine reconstructions that meet strict quality control criteria. We observe a cooling trend from 1 to 1800 CE that is robust against explicit tests for potential biases in the reconstructions. Between 801 and 1800 CE, the surface cooling trend is qualitatively consistent with an independent synthesis of terrestrial temperature reconstructions, and with a sea surface temperature composite derived from an ensemble of climate model simulations using best estimates of past external radiative forcings. Climate simulations using single and cumulative forcings suggest that the ocean surface cooling trend from 801 to 1800 CE is not primarily a response to orbital forcing but arises from a high frequency of explosive volcanism. Our results show that repeated clusters of volcanic eruptions can induce a net negative radiative forcing that results in a centennial and global scale cooling trend via a decline in mixed-layer oceanic heat content.
  • Moller, P, et al. (författare)
  • Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy
  • 2002
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons Inc.. - 0020-7136. ; 101:6, s. 555-559
  • Tidskriftsartikel (refereegranskat)abstract
    • Dedicated clinics have been established for the early diagnosis and treatment of women at risk for inherited breast cancer, but the effects of such interventions are currently unproven. This second report on prospectively diagnosed inherited breast cancer from the European collaborating centres supports the previous conclusions and adds information on genetic heterogeneity and the effect of oophorectomy. Of 249 patients, 20% had carcinoma in situ (CIS), 54% had infiltrating cancer without spread (CaNO) and 26% had cancer with spread (CaN+). Five-year survival was 100% for CIS, 94% for CaNO and 72% for CaN+ (p = 0.007). Thirty-six patients had BRCA1 mutations, and 8 had BRCA2 mutations. Presence of BRCA1 mutation was associated with infiltrating cancer, high grade and lack of oestrogen receptor (p < 0.05 for all 3 characteristics). For BRCA1 mutation carriers, 5-year survival was 63% vs. 91% for noncarriers (p = 0.04). For CaNO patients, mutation carriers had 75% S-year disease-free survival vs. 96% for noncarriers (p = 0.01). Twenty-one of the mutation carriers had undergone prophylactic oophorectomy, prior to or within 6 months of diagnosis in 13 cases. All but I relapse occurred in the I S who had kept their ovaries, (p < 0.01); no relapse occurred in those who had removed the ovaries within 6 months (p = 0.04) Contralateral cancer was more frequently observed in mutation noncarriers, but this finding did not reach statistical significance. Our findings support the concept that BRCA1 cancer is biologically different from other inherited breast cancers. While current screening protocols appear satisfactory for the majority of women at risk of familial breast cancer, this may not be the case for BRCA1 mutation carriers. The observed effect of oophorectomy was striking.
  • Moore, S., et al. (författare)
  • APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons
  • 2015
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 11:5, s. 689-696
  • Tidskriftsartikel (refereegranskat)abstract
    • Accumulation of A beta peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic A beta peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by beta-secretase and gamma-secretase inhibition, as well as gamma-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular A beta signaling to neurons.
  • Neukom, Raphael, et al. (författare)
  • Consistent multidecadal variability in global temperature reconstructions and simulations over the Common Era
  • 2019
  • Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 12:8, s. 643-
  • Tidskriftsartikel (refereegranskat)abstract
    • Multidecadal surface temperature changes may be forced by natural as well as anthropogenic factors, or arise unforced from the climate system. Distinguishing these factors is essential for estimating sensitivity to multiple climatic forcings and the amplitude of the unforced variability. Here we present 2,000-year-long global mean temperature reconstructions using seven different statistical methods that draw from a global collection of temperature-sensitive palaeoclimate records. Our reconstructions display synchronous multidecadal temperature fluctuations that are coherent with one another and with fully forced millennial model simulations from the Coupled Model Intercomparison Project Phase 5 across the Common Era. A substantial portion of pre-industrial (1300-1800 CE) variability at multidecadal timescales is attributed to volcanic aerosol forcing. Reconstructions and simulations qualitatively agree on the amplitude of the unforced global mean multidecadal temperature variability, thereby increasing confidence in future projections of climate change on these timescales. The largest warming trends at timescales of 20 years and longer occur during the second half of the twentieth century, highlighting the unusual character of the warming in recent decades.
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