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| 2. |
- 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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| 3. |
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| 4. |
- 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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| 5. |
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| 6. |
- Abe, K., et al.
(författare)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Rapport (refereegranskat)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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| 7. |
- Tanaka, Y. K., et al.
(författare)
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Search for eta '-mesic nuclei using (p,d) reaction with FRS/Super-FRS at GSI/FAIR
- 2020
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Ingår i: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1643
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Tidskriftsartikel (refereegranskat)abstract
- We plan a semi-exclusive measurement of the C-12(p,dp) reaction to search for eta'-mesic nuclei, aiming at investigating in-medium properties of the eta'-meson. We employ a 2.5 GeV proton beam impinging on a carbon target to produce eta'-mesic C-11 nuclei via the C-12(p,d)eta'circle times C-11 reaction. Using coincidence measurements of the forward going deuterons, important for missing-mass spectroscopy, and decay protons emitted from the eta'-mesic nuclei for event selection will provide a high experimental sensitivity to observe eta'-mesic nuclei. We will perform the measurements by combining the WASA detector system with the fragment separator FRS at GSI and also with the Super-FRS at FAIR in the future. The plan of the experiments and the present status are reported.
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| 8. |
- Chirapatpimol, K, et al.
(författare)
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Precision Measurement of the p(e,e′p)π0 Reaction at Threshold
- 2015
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Ingår i: Physical Review Letters. - 1079-7114. ; 114:19
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Tidskriftsartikel (refereegranskat)abstract
- New results are reported from a measurement of π^{0} electroproduction near threshold using the p(e,e^{'}p)π^{0} reaction. The experiment was designed to determine precisely the energy dependence of s- and p-wave electromagnetic multipoles as a stringent test of the predictions of chiral perturbation theory (ChPT). The data were taken with an electron beam energy of 1192 MeV using a two-spectrometer setup in Hall A at Jefferson Lab. For the first time, complete coverage of the ϕ_{π}^{*} and θ_{π}^{*} angles in the pπ^{0} center of mass was obtained for invariant energies above threshold from 0.5 up to 15 MeV. The 4-momentum transfer Q^{2} coverage ranges from 0.05 to 0.155 (GeV/c)^{2} in fine steps. A simple phenomenological analysis of our data shows strong disagreement with p-wave predictions from ChPT for Q^{2}>0.07 (GeV/c)^{2}, while the s-wave predictions are in reasonable agreement.
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| 9. |
- Fujita, S., et al.
(författare)
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Spatial and temporal variability of snow accumulation rate on the East Antarctic ice divide between Dome Fuji and EPICA DML
- 2011
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Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 5:4, s. 1057-1081
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Tidskriftsartikel (refereegranskat)abstract
- To better understand the spatio-temporal variability of the glaciological environment in Dronning Maud Land (DML), East Antarctica, a 2800-km-long Japanese-Swedish traverse was carried out. The route includes ice divides between two ice-coring sites at Dome Fuji and EPICA DML. We determined the surface mass balance (SMB) averaged over various time scales in the late Holocene based on studies of snow pits and firn cores, in addition to radar data. We find that the large-scale distribution of the SMB depends on the surface elevation and continentality, and that the SMB differs between the windward and leeward sides of ice divides for strong-wind events. We suggest that the SMB is highly influenced by interactions between the large-scale surface topography of ice divides and the wind field of strong-wind events that are often associated with high-precipitation events. Local variations in the SMB are governed by the local surface topography, which is influenced by the bedrock topography. In the eastern part of DML, the accumulation rate in the second half of the 20th century is found to be higher by similar to 15% than averages over longer periods of 722 a or 7.9 ka before AD 2008. A similar increasing trend has been reported for many inland plateau sites in Antarctica with the exception of several sites on the leeward side of the ice divides.
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