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Sökning: WFRF:(Robertson Neil) > Stockholms universitet

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1.
  • Dussex, Nicolas, et al. (författare)
  • Population genomics of the critically endangered kākāpō
  • 2021
  • Ingår i: Cell Genomics. - : Elsevier BV. - 2666-979X. ; 1:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary The kākāpō is a flightless parrot endemic to New Zealand. Once common in the archipelago, only 201 individuals remain today, most of them descending from an isolated island population. We report the first genome-wide analyses of the species, including a high-quality genome assembly for kākāpō, one of the first chromosome-level reference genomes sequenced by the Vertebrate Genomes Project (VGP). We also sequenced and analyzed 35 modern genomes from the sole surviving island population and 14 genomes from the extinct mainland population. While theory suggests that such a small population is likely to have accumulated deleterious mutations through genetic drift, our analyses on the impact of the long-term small population size in kākāpō indicate that present-day island kākāpō have a reduced number of harmful mutations compared to mainland individuals. We hypothesize that this reduced mutational load is due to the island population having been subjected to a combination of genetic drift and purging of deleterious mutations, through increased inbreeding and purifying selection, since its isolation from the mainland ∼10,000 years ago. Our results provide evidence that small populations can survive even when isolated for hundreds of generations. This work provides key insights into kākāpō breeding and recovery and more generally into the application of genetic tools in conservation efforts for endangered species.
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2.
  • Campbell, Rochelle, et al. (författare)
  • BLUE INTENSITY IN PINUS SYLVESTRIS TREE RINGS : A MANUAL FOR A NEW PALAEOCLIMATE PROXY
  • 2011
  • Ingår i: TREE-RING RESEARCH. - : Tree-Ring Society. - 1536-1098. ; 67:2, s. 127-134
  • Tidskriftsartikel (refereegranskat)abstract
    • Minimum blue intensity is a reflected light imaging technique that provides an inexpensive, robust and reliable surrogate for maximum latewood density. In this application it was found that temperature reconstructions from resin-extracted samples of Pious sylvestris (L.) from Fennoscandia provide results equivalent to conventional x-ray densitometry. This paper describes the implementation of the blue intensity method using commercially available software and a flat-bed scanner. A calibration procedure is presented that permits results obtained by different laboratories, or using different scanners, to be compared. In addition, the use of carefully prepared and chemically treated 10-mm-diameter cores are explored; suggesting that it may not be necessary to produce thin laths with the rings aligned exactly perpendicular to the measurement surface.
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3.
  • Dawed, Adem Y., et al. (författare)
  • Pharmacogenomics of GLP-1 receptor agonists : a genome- wide analysis of observational data and large randomised controlled trials
  • 2023
  • Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 11:1, s. 33-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In the treatment of type 2 diabetes, GLP-1 receptor agonists lower blood glucose concentrations, body weight, and have cardiovascular benefits. The efficacy and side effects of GLP-1 receptor agonists vary between people. Human pharmacogenomic studies of this inter-individual variation can provide both biological insight into drug action and provide biomarkers to inform clinical decision making. We therefore aimed to identify genetic variants associated with glycaemic response to GLP-1 receptor agonist treatment. Methods:In this genome-wide analysis we included adults (aged & GE;18 years) with type 2 diabetes treated with GLP-1 receptor agonists with baseline HbA1c of 7% or more (53 mmol/mol) from four prospective observational cohorts (DIRECT, PRIBA, PROMASTER, and GoDARTS) and two randomised clinical trials (HARMONY phase 3 and AWARD). The primary endpoint was HbA1c reduction at 6 months after starting GLP-1 receptor agonists. We evaluated variants in GLP1R, then did a genome-wide association study and gene-based burden tests. Findings:4571 adults were included in our analysis, of these, 3339 (73%) were White European, 449 (10%) Hispanic, 312 (7%) American Indian or Alaskan Native, and 471 (10%) were other, and around 2140 (47%) of the participants were women. Variation in HbA1c reduction with GLP-1 receptor agonists treatment was associated with rs6923761G & RARR;A (Gly168Ser) in the GLP1R (0.08% [95% CI 0.04-0.12] or 0.9 mmol/mol lower reduction in HbA1c per serine, p=6.0 x 10-5) and low frequency variants in ARRB1 (optimal sequence kernel association test p=6.7 x 10-8), largely driven by rs140226575G & RARR;A (Thr370Met; 0.25% [SE 0.06] or 2.7 mmol/mol [SE 0.7] greater HbA1c reduction per methionine, p=5.2 x 10-6). A similar effect size for the ARRB1 Thr370Met was seen in Hispanic and American Indian or Alaska Native populations who have a higher frequency of this variant (6-11%) than in White European populations. Combining these two genes identified 4% of the population who had a 30% greater reduction in HbA1c than the 9% of the population with the worse response. Interpretation:This genome-wide pharmacogenomic study of GLP-1 receptor agonists provides novel biological and clinical insights. Clinically, when genotype is routinely available at the point of prescribing, individuals with ARRB1 variants might benefit from earlier initiation of GLP-1 receptor agonists.
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4.
  • Gagen, Mary, et al. (författare)
  • Cloud response to summer temperatures in Fennoscandia over the last thousand years
  • 2011
  • Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 38, s. L05701-
  • Tidskriftsartikel (refereegranskat)abstract
    • Cloud cover is one of the most important factors controlling the radiation balance of the Earth. The response of cloud cover to increasing global temperatures represents the largest uncertainty in model estimates of future climate because the cloud response to temperature is not well-constrained. Here we present the first regional reconstruction of summer sunshine over the past millennium, based on the stable carbon isotope ratios of pine treerings from Fennoscandia. Comparison with the regional temperature evolution reveals the Little Ice Age (LIA) to have been sunny, with cloudy conditions in the warmest periods of the Medieval at this site. A negative shortwave cloud feedback is indicated at high latitude. A millennial climate simulation suggests that regionally low temperatures during the LIA were mostly maintained by a weaker greenhouse effect due to lower humidity. Simulations of future climate that display a negative shortwave cloud feedback for high-latitudes are consistent with our proxy interpretation. Citation: Gagen, M., E. Zorita, D. McCarroll, G. H. F. Young, H. Grudd, R. Jalkanen, N. J. Loader, I. Robertson, and A. Kirchhefer (2011), Cloud response to summer temperatures in Fennoscandia over the last thousand years, Geophys. Res. Lett., 38, L05701, doi:10.1029/2010GL046216.
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5.
  • Gaulton, Kyle J, et al. (författare)
  • Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
  • 2015
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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6.
  • Kaislahti Tillman, Päivi, 1958-, et al. (författare)
  • Stable carbon and oxygen isotopes in Sphagnum fuscum peat from subarctic Canada : implications for palaeoclimate studies
  • 2010
  • Ingår i: Chemical Geology. - : Elsevier BV. - 0009-2541 .- 1872-6836. ; 270:1-4, s. 216-226
  • Tidskriftsartikel (refereegranskat)abstract
    • Stable carbon and oxygen isotope ratios in single plant components in Sphagnum peat have a good potential to reveal environmental changes in peat archives. Two peat profiles, covering the past ~6000 years, and a Sphagnum hummock from a discontinuous permafrost area in west central Canada were studied in order to evaluate the effect of decomposition rate on isotope records and to assess which plant components are most suitable for climate reconstructions. The stable isotope values from the most recently forming Sphagnum tissues were compared with observational climate data to study the impact of variations in temperature and precipitation on the peat isotopes. Our results show that there is high correlation between δ13C values in α-cellulose isolated from Sphagnum fuscum stems and summer temperatures, whereas δ18O in the plant tissues is controlled by several factors, such as summer precipitation, summer temperature and evaporation. According to our results, decomposition as derived from C/N values and colorimetry does not seem to affect the oxygen and carbon isotope values of α-cellulose from Sphagnum fuscum peat significantly. There is, however, a (quasi-) constant offset between the isotope values of branches and stems and between whole plant material and  α-cellulose, which makes it crucial to select single moss-fractions when past climate and environmental changes are to be derived from the isotope record.
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7.
  • Martini, Denise, et al. (författare)
  • Evolution of the “world’s only alpine parrot” : Genomic adaptation or phenotypic plasticity, behaviour and ecology?
  • 2021
  • Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 30:23, s. 6370-6386
  • Tidskriftsartikel (refereegranskat)abstract
    • Climate warming, in particular in island environments, where opportunities for species to disperse are limited, may become a serious threat to cold adapted alpine species. In order to understand how alpine species may respond to a warming world, we need to understand the drivers that have shaped their habitat specialisation and the evolutionary adaptations that allow them to utilize alpine habitats. The endemic, endangered New Zealand kea (Nestor notabilis) is considered the only alpine parrot in the world. As a species commonly found in the alpine zone it may be highly susceptible to climate warming. But is it a true alpine specialist? Is its evolution driven by adaptation to the alpine zone, or is the kea an open habitat generalist that simply uses the alpine zone to, for example, avoid lower lying anthropogenic landscapes? We use whole genome data of the kea and its close, forest adapted sister species, the kākā (Nestor meridionalis) to reconstruct the evolutionary history of both species and identify the functional genomic differences that underlie their habitat specialisations. Our analyses do not identify major functional genomic differences between kea and kākā in pathways associated with high-altitude. Rather, we found evidence that selective pressures on adaptations commonly found in alpine species are present in both Nestor species, suggesting that selection for alpine adaptations has not driven their divergence. Strongly divergent demographic responses to past climate warming between the species nevertheless highlight potential future threats to kea survival in a warming world.
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8.
  • Mccarroll, Danny, et al. (författare)
  • A critical evaluation of multi-proxy dendroclimatology in northern Finland
  • 2011
  • Ingår i: Journal of Quaternary Science. - : Wiley. - 0267-8179 .- 1099-1417. ; 26:1, s. 7-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Twentieth-century summer (July-August) temperatures in northern Finland are reconstructed using ring widths, maximum density and stable carbon isotope ratios (delta(13)C) of Scots pine tree rings, and using combinations of these proxies. Verification is based on the coefficient of determination (r(2)), reduction of error (RE) and coefficient of efficiency (CE) statistics. Of the individual proxies, delta(13)C performs best, followed by maximum density. Combining delta(13)C and maximum density strengthens the climate signal but adding ring widths leads to little improvement. Blue intensity, an inexpensive alternative to X-ray densitometry, is shown to perform similarly. Multi-proxy reconstruction of summer temperatures from a single site produces strong correlations with gridded climate data over most of northern Fennoscandia. Since relatively few trees are required (<15) the approach could be applied to long sub-fossil chronologies where replication may be episodically low.
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9.
  • Saurer, Matthias, et al. (författare)
  • Spatial variability and temporal trends in water-use efficiency of European forests
  • 2014
  • Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 20:12, s. 3700-3712
  • Tidskriftsartikel (refereegranskat)abstract
    • The increasing carbon dioxide (CO2) concentration in the atmosphere in combination with climatic changes throughout the last century are likely to have had a profound effect on the physiology of trees: altering the carbon and water fluxes passing through the stomatal pores. However, the magnitude and spatial patterns of such changes in natural forests remain highly uncertain. Here, stable carbon isotope ratios from a network of 35 tree-ring sites located across Europe are investigated to determine the intrinsic water-use efficiency (iWUE), the ratio of photosynthesis to stomatal conductance from 1901 to 2000. The results were compared with simulations of a dynamic vegetation model (LPX-Bern 1.0) that integrates numerous ecosystem and land-atmosphere exchange processes in a theoretical framework. The spatial pattern of tree-ring derived iWUE of the investigated coniferous and deciduous species and the model results agreed significantly with a clear south-to-north gradient, as well as a general increase in iWUE over the 20th century. The magnitude of the iWUE increase was not spatially uniform, with the strongest increase observed and modelled for temperate forests in Central Europe, a region where summer soil-water availability decreased over the last century. We were able to demonstrate that the combined effects of increasing CO2 and climate change leading to soil drying have resulted in an accelerated increase in iWUE. These findings will help to reduce uncertainties in the land surface schemes of global climate models, where vegetation-climate feedbacks are currently still poorly constrained by observational data.
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10.
  • Scott, Robert A., et al. (författare)
  • An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
  • 2017
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:11, s. 2888-2902
  • Tidskriftsartikel (refereegranskat)abstract
    • To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
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