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- 2019
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Tidskriftsartikel (refereegranskat)
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- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 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
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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- Bustamante, Mercedes, et al.
(författare)
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Ten New Insights in Climate Science 2023/2024
- 2023
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Ingår i: Global Sustainability. - 2059-4798.
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Tidskriftsartikel (refereegranskat)abstract
- Non-technical summary: We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems. Technical summary The IPCC Assessment Reports offer the scientific foundation for international climate negotiations and constitute an unmatched resource for climate change researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding across diverse climate change research communities, we have streamlined an annual process to identify and synthesise essential research advances. We collected input from experts on different fields using an online questionnaire and prioritised a set of ten key research insights with high policy relevance. This year we focus on: (1) looming overshoot of the 1.5°C warming limit, (2) urgency of phasing-out fossil fuels, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future of natural carbon sinks, (5) need for join governance of biodiversity loss and climate change, (6) advances in the science of compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems. We first present a succinct account of these Insights, reflect on their policy implications, and offer an integrated set of policy relevant messages. This science synthesis and science communication effort is also the basis for a report targeted to policymakers as a contribution to elevate climate science every year, in time for the UNFCCC COP. Social media summary We highlight recent and policy-relevant advances in climate change research - with input from more than 200 experts 1.
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- Maxwell, Christopher A., et al.
(författare)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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- Yu, Hoi-Fung, et al.
(författare)
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Synchrotron cooling in energetic gamma-ray bursts observed by the Fermi Gamma-Ray Burst Monitor
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 573
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Tidskriftsartikel (refereegranskat)abstract
- Context. We study the time-resolved spectral properties of energetic gamma-ray bursts (GRBs) with good high-energy photon statistics observed by the Gamma-Ray Burst Monitor ((IBM) onboard the Fermi Gamma-Ray Space Telescope. Aims. We aim to constrain in detail the spectral properties of GRB prompt emission on a time-resolved basis and to discuss the theoretical implications of the fitting results in the context of various prompt emission models. Methods. Our sample comprises eight GRBs observed by the Fermi (IBM in its first five years of mission, with 1 keV-1 MeV fluence f > 1.0 x 10(-4) erg cm(-2) and a signal-to-noise ratio level of S/N >= 10.0 above 900 keV. We performed a time-resolved spectral analysis using a variable temporal binning technique according to optimal S/N criteria, resulting in a total of 299 time-resolved spectra. We performed Band function fits to all spectra and obtained the distributions for the low-energy power-lay index alpha, the high-energy power-law index beta, the peak energy in the observed nu F-nu, spectrum E-p, and the difference between the low- and high-energy power-law indices Delta s = alpha-beta. We also applied a physically motivated synchrotron model, which is a triple power-law with constrained power-law indices and a blackbody component, to test the prompt emission for consistency with a synchrotron origin and obtain the distributions for the two break energies E-b,E-1 and E-b,E-2 the middle segment power-law index beta, and the Planck function temperature kT. Results. The Band function parameter distributions are alpha = -0.73(-0.21)(+0.16), beta = -2.13(-0.56)(+0.28), E-p = 374.47(-187.7)(+307.3) keV (log(10) E-p = 2.577(-0.30)(+0.26)), and Delta s = 1.38(-0.31)(+0.54), with average errors sigma(alpha) similar to 0.1, sigma(beta) similar to 0.2, and sigma(Ep) similar to 0.1E(p). Using the distributions of Delta s and beta, the electron population index p is found to be consistent with the "moderately fast" scenario, in which fast- and slow-cooling scenarios cannot be distinguished. The physically motivated synchrotron-fitting function parameter distributions are E-b,E-1 = 129.6(-32.4)(+132.2) keV, E-b,E-2 = 631.4(-309.6)(+582) keV, beta = 1.721(-0.25)(+0.48), and kT = 10.4(-3.7)(+4.9) keV, with average errors sigma(beta) similar to 0.2, sigma E-b,E-1 similar to 0.1E(b,1), sigma E-b,E-2 similar to 0.4E(b,2,) and sigma(kT) similar to 0.1kT. This synchrotron function requires the synchrotron injection and cooling break (i.e., E-min and E-cool) to be close to each other within a factor of ten, often in addition to a Planck function. Conclusions. A synchrotron model is found that is consistent with most of the time-resolved spectra for eight energetic Fermi (IBM bursts with good high-energy photon statistics as long as both the cooling and injection break are included and the leftmost spectral slope is lifted either by including a thermal component or when an evolving magnetic field is accounted for.
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