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| 12. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 13. |
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| 14. |
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| 15. |
- Graff, M., et al.
(författare)
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Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- 2017
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Ingår i: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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| 16. |
- Sun, S., et al.
(författare)
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Inhibition of the Activation and Recruitment of Microglia-Like Cells Protects Against Neomycin-Induced Ototoxicity
- 2015
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Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 51:1, s. 252-267
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Tidskriftsartikel (refereegranskat)abstract
- One of the most unfortunate side effects of aminoglycoside (AG) antibiotics such as neomycin is that they target sensory hair cells (HCs) and can cause permanent hearing impairment. We have observed HC loss and microglia-like cell (MLC) activation in the inner ear (cochlea) following neomycin administration. We focused on CX3CL1, a membrane-bound glycoprotein expressed on neurons and endothelial cells, as a way to understand how the MLCs are activated and the role these cells play in HC loss. CX3CL1 is the exclusive ligand for CX3CR1, which is a chemokine receptor expressed on the surface of macrophages and MLCs. In vitro experiments showed that the expression levels of CX3CL1 and CX3CR1 increased in the cochlea upon neomycin treatment, and CX3CL1 was expressed on HCs, while CX3CR1 was expressed on MLCs. When cultured with 1 mu g/mL exogenous CX3CL1, MLCs were activated by CX3CL1, and the cytokine level was increased in the cochleae leading to apoptosis in the HCs. In CX3CR1 knockout mice, a significantly greater number of cochlear HCs survived than in wild-type mice when the cochlear explants were cultured with neomycin in vitro. Furthermore, inhibiting the activation of MLCs with minocycline reduced the neomycin-induced HC loss and improved the hearing function in neomycin-treated mice in vivo. Our results demonstrate that CX3CL1-induced MLC activation plays an important role in the induction of HC death and provide evidence for CX3CL1 and CX3CR1 as promising new therapeutic targets for the prevention of hearing loss.
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| 17. |
- Wang, L., et al.
(författare)
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Development of a land surface model with coupled snow and frozen soil physics
- 2017
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Ingår i: Water Resources Research. - : American Geophysical Union (AGU). - 0043-1397 .- 1944-7973. ; 53:6, s. 5085-5103
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Tidskriftsartikel (refereegranskat)abstract
- Snow and frozen soil are important factors that influence terrestrial water and energy balances through snowpack accumulation and melt and soil freeze-thaw. In this study, a new land surface model (LSM) with coupled snow and frozen soil physics was developed based on a hydrologically improved LSM (HydroSiB2). First, an energy-balance-based three-layer snow model was incorporated into HydroSiB2 (hereafter HydroSiB2-S) to provide an improved description of the internal processes of the snow pack. Second, a universal and simplified soil model was coupled with HydroSiB2-S to depict soil water freezing and thawing (hereafter HydroSiB2-SF). In order to avoid the instability caused by the uncertainty in estimating water phase changes, enthalpy was adopted as a prognostic variable instead of snow/soil temperature in the energy balance equation of the snow/frozen soil module. The newly developed models were then carefully evaluated at two typical sites of the Tibetan Plateau (TP) (one snow covered and the other snow free, both with underlying frozen soil). At the snow-covered site in northeastern TP (DY), HydroSiB2-SF demonstrated significant improvements over HydroSiB2-F (same as HydroSiB2-SF but using the original single-layer snow module of HydroSiB2), showing the importance of snow internal processes in three-layer snow parameterization. At the snow-free site in southwestern TP (Ngari), HydroSiB2-SF reasonably simulated soil water phase changes while HydroSiB2-S did not, indicating the crucial role of frozen soil parameterization in depicting the soil thermal and water dynamics. Finally, HydroSiB2-SF proved to be capable of simulating upward moisture fluxes toward the freezing front from the underlying soil layers in winter.
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| 18. |
- Justice, A. E., et al.
(författare)
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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| 19. |
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| 20. |
- Ruffini, R., et al.
(författare)
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Early X-Ray Flares in GRBs
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 852:1
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Tidskriftsartikel (refereegranskat)abstract
- We analyze the early X-ray flares in the GRB flare-plateau-afterglow (FPA) phase observed by Swift-XRT. The FPA occurs only in one of the seven GRB subclasses: the binary-driven hypernovae (BdHNe). This subclass consists of long GRBs with a carbon-oxygen core and a neutron star (NS) binary companion as progenitors. The hypercritical accretion of the supernova (SN) ejecta onto the NS can lead to the gravitational collapse of the NS into a black hole. Consequently, one can observe a GRB emission with isotropic energy E-iso greater than or similar to 10(52) erg, as well as the associated GeV emission and the FPA phase. Previous work had shown that gamma-ray spikes in the prompt emission occur at similar to 10(15)-10(17) cm with Lorentz Gamma factors Gamma similar to 10(2)-10(3). Using a novel data analysis, we show that the time of occurrence, duration, luminosity, and total energy of the X-ray flares correlate with E-iso. A crucial feature is the observation of thermal emission in the X-ray flares that we show occurs at radii similar to 10(12) cm with Gamma less than or similar to 4. These model-independent observations cannot be explained by the fireball model, which postulates synchrotron and inverse-Compton radiation from a single ultrarelativistic jetted emission extending from the prompt to the late afterglow and GeV emission phases. We show that in BdHNe a collision between the GRB and the SN ejecta occurs at similar or equal to 10(10) cm, reaching transparency at similar to 10(12) cm with Gamma less than or similar to 4. The agreement between the thermal emission observations and these theoretically derived values validates our model and opens the possibility of testing each BdHN episode with the corresponding Lorentz Gamma factor.
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