| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 4. |
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| 5. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 6. |
- Abdalla, H., et al.
(författare)
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HESS observations of RX J1713.7-3946 with improved angular and spectral resolution : Evidence for gamma-ray emission extending beyond the X-ray emitting shell
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
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Tidskriftsartikel (refereegranskat)abstract
- Supernova remnants exhibit shock fronts (shells) that can accelerate charged particles up to very high energies. In the past decade, measurements of a handful of shell-type supernova remnants in very high-energy gamma rays have provided unique insights into the acceleration process. Among those objects, RX J1713.7-3946 (also known as G347.3-0.5) has the largest surface brightness, allowing us in the past to perform the most comprehensive study of morphology and spatially resolved spectra of any such very high-energy gamma-ray source. Here we present extensive new H.E.S.S. measurements of RX J1713.7-3946, almost doubling the observation time compared to our previous publication. Combined with new improved analysis tools, the previous sensitivity is more than doubled. The H.E.S.S. angular resolution of 0.048 degrees (0.036 degrees above 2 TeV) is unprecedented in gamma-ray astronomy and probes physical scales of 0.8 (0.6) parsec at the remnant's location. The new H. E. S. S. image of RX J1713.7-3946 allows us to reveal clear morphological di ff erences between X-rays and gamma rays. In particular, for the outer edge of the brightest shell region, we find the first ever indication for particles in the process of leaving the acceleration shock region. By studying the broadband energy spectrum, we furthermore extract properties of the parent particle populations, providing new input to the discussion of the leptonic or hadronic nature of the gamma-ray emission mechanism.
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| 7. |
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| 8. |
- Na, Yong-Su, et al.
(författare)
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On benchmarking of simulations of particle transport in ITER
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:7
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Tidskriftsartikel (refereegranskat)abstract
- We report results of benchmarking of core particle transport simulations by a collection of codes widely used in transport modelling of tokamak plasmas. Our analysis includes formulation of transport equations, difference between electron and ion solvers, comparison of modules of the pellet and edge gas fuelling on the ITER baseline scenario. During the first phase of benchmarking we address the particle transport effects in the stationary phase. Firstly, simulations are performed with identical sources, sinks, transport coefficients, and boundary conditions prescribed in the flattop H-mode phase. The transformation of ion particle transport equations is introduced so to directly compare their results to electron transport solvers. Secondly, the pellet fuelling models are benchmarked in various conditions to evaluate the dependency of the pellet deposition on the pellet volume, injection side, pedestal, and separatrix parameters. Thirdly, edge gas fuelling is benchmarked to assess sensitivities of source profile predictions to uncertainties in plasma conditions and detailed model assumptions. At the second phase, we address particle transport effects in the time- evolving plasma including the current ramp-up to the ramp-down phase. The ion and the electron solvers are benchmarked together. Differences between the simulation results of the solvers are investigated in terms of equilibrium, grid resolution, radial coordinate, radial grid distribution, and plasma volume evolution term. We found that the selection of the radial coordinate can yield prominent differences between the solvers mainly due to differences in the edge grid distribution. The simulations reveal that electron and ion solvers predict noticeably different density peaking for the same diffusion and pinch velocity while with the peaked profile of helium, expected in fusion reactors. The fuelling benchmarking shows that gas puffing is not efficient for core fuelling in H-modes and density control should be done by the high field side pellet injection in contrast to present machines.
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