| 1. |
- Lumbers, R. T., et al.
(författare)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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| 2. |
- Shah, S, et al.
(författare)
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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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| 3. |
- Oieroset, M., et al.
(författare)
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Spatial evolution of magnetic reconnection diffusion region structures with distance from the X-line
- 2021
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Ingår i: Physics of Plasmas. - : American Institute of Physics (AIP). - 1070-664X .- 1089-7674. ; 28:12
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Tidskriftsartikel (refereegranskat)abstract
- We report Magnetospheric Multiscale four-spacecraft observations of a thin reconnecting current sheet with weakly asymmetric inflow conditions and a guide field of approximately twice the reconnecting magnetic field. The event was observed at the interface of interlinked magnetic field lines at the flank magnetopause when the maximum spacecraft separation was 370 km and the spacecraft covered & SIM;1.7 ion inertial lengths (d(i)) in the reconnection outflow direction. The ion-scale spacecraft separation made it possible to observe the transition from electron-only super ion-Alfvenic outflow near the electron diffusion region (EDR) to the emergence of sub-Alfvenic ion outflow in the ion diffusion region (IDR). The EDR to IDR evolution over a distance less than 2 d(i) also shows the transition from a near-linear reconnecting magnetic field reversal to a more bifurcated current sheet as well as significant decreases in the parallel electric field and dissipation. Both the ion and electron heating in this diffusion region event were similar to the previously reported heating in the far downstream exhausts. The dimensionless reconnection rate, obtained four different ways, was in the range of 0.13-0.27. This event reveals the rapid spatial evolution of the plasma and electromagnetic fields through the EDR to IDR transition region.& nbsp;(C) 2021 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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| 4. |
- Johlander, Andreas, 1990-, et al.
(författare)
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Ion Acceleration Efficiency at the Earth's Bow Shock : Observations and Simulation Results
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 914:2
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Tidskriftsartikel (refereegranskat)abstract
- Collisionless shocks are some of the most efficient particle accelerators in heliospheric and astrophysical plasmas. Here we study and quantify ion acceleration at Earth's bow shock with observations from NASA's Magnetospheric Multiscale (MMS) satellites and in a global hybrid-Vlasov simulation. From the MMS observations, we find that quasiparallel shocks are more efficient at accelerating ions. There, up to 15% of the available energy goes into accelerating ions above 10 times their initial energy. Above a shock-normal angle of similar to 50 degrees, essentially no energetic ions are observed downstream of the shock. We find that ion acceleration efficiency is significantly lower when the shock has a low Mach number (M ( A ) < 6) while there is little Mach number dependence for higher values. We also find that ion acceleration is lower on the flanks of the bow shock than at the subsolar point regardless of the Mach number. The observations show that a higher connection time of an upstream field line leads to somewhat higher acceleration efficiency. To complement the observations, we perform a global hybrid-Vlasov simulation with realistic solar-wind parameters with the shape and size of the bow shock. We find that the ion acceleration efficiency in the simulation shows good quantitative agreement with the MMS observations. With the combined approach of direct spacecraft observations, we quantify ion acceleration in a wide range of shock angles and Mach numbers.
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| 5. |
- Dussex, Nicolas, et al.
(författare)
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Population genomics of the critically endangered kākāpō
- 2021
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Ingår i: Cell Genomics. - : Elsevier BV. - 2666-979X. ; 1:1
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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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