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Sökning: WFRF:(Eriksson Anders) > Annan publikation

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  • Klaric, Lucija, et al. (författare)
  • Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
  • 2021
  • Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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  • Mutschler, Diana K., et al. (författare)
  • Riksstämman 2001
  • 2001
  • Annan publikation (övrigt vetenskapligt/konstnärligt)
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  • Sahlberg, Arne, et al. (författare)
  • Analysis of the neutron spectrum from T+T reactions in NBI-heated fusion plasmas at JET
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • In tritium (T) plasma experiments at the tokamak JET, the neutron emission spectrum has been measured with the time-of-flight spectrometer TOFOR and analyzed to determine the probability for the short-lived 5He resonance occurring in T+T reactions. Using a component-based model of the neutron emission from the T+T and D+T reactions present in a tritium plasma at JET, with trace deuterium, and fitting said model to the measured time-of-flight spectrum, we estimate the branching ratio for the different T+T reactions.From an analysis of TOFOR data from 33 NBI-heated tritium discharges, we learn that the ground state 5He-resonance occurs in 5.8(15)% of the T+T reactions at COM energies in the range 50-100 keV. These results fall in line with previous most measurements done at particle accelerators and inertial confinement fusion reactors.Apart from providing increased insight into the physics of the T+T reaction, the value of the branching ratio obtained in this study can lead to improved models of the neutron emission spectrum from tokamaks, and aid in the interpretation of neutron measurements from future T and DT experiments.
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  • Resultat 1-10 av 98
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