| 1. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 2. |
- Hunsicker, Mary E., et al.
(författare)
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Functional responses and scaling in predator-prey interactions of marine fishes : contemporary issues and emerging concepts
- 2011
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Ingår i: Ecology Letters. - : Wiley-Blackwell. - 1461-023X .- 1461-0248. ; 14:12, s. 1288-1299
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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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| 3. |
- Kara, Emily L., et al.
(författare)
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Time-scale dependence in numerical simulations : Assessment of physical, chemical, and biological predictions in a stratified lake at temporal scales of hours to months
- 2012
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Ingår i: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152 .- 1873-6726. ; 35, s. 104-121
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the predictive ability of a one-dimensional coupled hydrodynamic-biogeochemical model across multiple temporal scales using wavelet analysis and traditional goodness-of-fit metrics. High-frequency in situ automated sensor data and long-term manual observational data from Lake Mendota, Wisconsin, USA, were used to parameterize, calibrate, and evaluate model predictions. We focused specifically on short-term predictions of temperature, dissolved oxygen, and phytoplankton biomass over one season. Traditional goodness-of-fit metrics indicated more accurate prediction of physics than chemical or biological variables in the time domain. This was confirmed by wavelet analysis in both the time and frequency domains. For temperature, predicted and observed global wavelet spectra were closely related, while observed dissolved oxygen and chlorophyll fluorescence spectral characteristics were not reproduced by the model for key time scales, indicating that processes not modeled may be important drivers of the observed signal. Although the magnitude and timing of physical and biological changes were simulated adequately at the seasonal time scale through calibration, time scale-specific dynamics, for example short-term cycles, were difficult to reproduce, and were relatively insensitive to the effects of varying parameters. The use of wavelet analysis is novel to aquatic ecosystem modeling, is complementary to traditional goodness-of-fit metrics, and allows for assessment of variability at specific temporal scales. In this way, the effect of processes operating at distinct temporal scales can be isolated and better understood, both in situ and in silico. Wavelet transforms are particularly well suited for assessment of temporal and spatial heterogeneity when coupled to high-frequency data from automated in situ or remote sensing platforms.
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| 4. |
- Rahman, Cheryl V., et al.
(författare)
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PLGA/PEG-hydrogel composite scaffolds with controllable mechanical properties
- 2013
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Ingår i: Journal of Biomedical Materials Research. Part B - Applied biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 101B:4, s. 648-655
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Tidskriftsartikel (refereegranskat)abstract
- Biodegradable polymer scaffolds have great potential for regenerative medicine applications such as the repair of musculoskeletal tissues. Here, we describe the development of scaffolds that blend hydrogel components with thermoplastic materials, combining the unique properties of both components to create mouldable formulations. This study focuses on the structural and mechanical properties of the composite scaffolds, produced by combining temperature-sensitive poly(DL-lactic acid-co-glycolic acid) (PLGA)/poly(ethylene glycol) (PEG) particles with a hydrogel component [Pluronic F127, fibrin or hyaluronic acid (HyA)]. The composite formulations solidified over time at 37 degrees C, with a significant increase (p 0.05) in compressive strength observed from 15 min to 2 h at this temperature. The maximum compressive strength was 1.2 MPa for PLGA/PEG-Pluronic F127 scaffolds, 2.4 MPa for PLGA/PEG-HyA scaffolds and 0.6 MPa for PLGA/PEG-fibrin scaffolds. Porosity for each of the PLGA/PEG-hydrogel formulations tested was between 50 and 51%. This study illustrates the ability to combine this thermoplastic PLGA/PEG system with hydrogels to fabricate composite scaffolds, and demonstrates that altering the particle to hydrogel ratio produces scaffolds with varying mechanical properties.
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| 5. |
- Urayama, Kevin Y., et al.
(författare)
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Genome-Wide Association Study of Classical Hodgkin Lymphoma and Epstein-Barr Virus Status-Defined Subgroups
- 2012
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Ingår i: Journal of the National Cancer Institute. - Oxford : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 104:3, s. 240-253
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence suggests that risk factors for classical Hodgkin lymphoma (cHL) differ by tumor Epstein-Barr virus (EBV) status. This potential etiological heterogeneity is not recognized in current disease classification. We conducted a genome-wide association study of 1200 cHL patients and 6417 control subjects, with validation in an independent replication series, to identify common genetic variants associated with total cHL and subtypes defined by tumor EBV status. Multiple logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) assuming a log-additive genetic model for the variants. All statistical tests were two-sided. Two novel loci associated with total cHL irrespective of EBV status were identified in the major histocompatibility complex region; one resides adjacent to MICB (rs2248462: OR = 0.61, 95% CI = 0.53 to 0.69, P = 1.3 x 10(-13)) and the other at HLA-DRA (rs2395185: OR = 0.56, 95% CI = 0.50 to 0.62, P = 8.3 x 10(-25)) with both results confirmed in an independent replication series. Consistent with previous reports, associations were found between EBV-positive cHL and genetic variants within the class I region (rs2734986, HLA-A: OR = 2.45, 95% CI = 2.00 to 3.00, P = 1.2 x 10(-15); rs6904029, HCG9: OR = 0.46, 95% CI = 0.36 to 0.59, P = 5.5 x 10(-10)) and between EBV-negative cHL and rs6903608 within the class II region (rs6903608, HLA-DRA: OR = 2.08, 95% CI = 1.84 to 2.35, P = 6.1 x 10(-31)). The association between rs6903608 and EBV-negative cHL was confined to the nodular sclerosis histological subtype. Evidence for an association between EBV-negative cHL and rs20541 (5q31, IL13: OR = 1.53, 95% CI = 1.32 to 1.76, P = 5.4 x 10(-9)), a variant previously linked to psoriasis and asthma, was observed; however, the evidence for replication was less clear. Notably, one additional psoriasis-associated variant, rs27524 (5q15, ERAP1), showed evidence of an association with cHL in the genome-wide association study (OR = 1.21, 95% CI = 1.10 to 1.33, P = 1.5 x 10(-4)) and replication series (P = .03). Overall, these results provide strong evidence that EBV status is an etiologically important classification of cHL and also suggest that some components of the pathological process are common to both EBV-positive and EBV-negative patients.
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| 6. |
- Yang, Jian, et al.
(författare)
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FTO genotype is associated with phenotypic variability of body mass index
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 490:7419, s. 267-272
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using similar to 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)(5-7), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of similar to 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation(9,10). Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
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