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- 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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- 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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- Doornenbal, P., et al.
(författare)
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Spectroscopy of 32Ne and the "œIsland of Inversion"
- 2009
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Ingår i: Physical Review Letters. - American Physical Society. - 0031-9007 .- 1079-7114. ; 103:3, s. 032501-1-032501-4
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Tidskriftsartikel (refereegranskat)abstract
- We report on the first spectroscopic study of the N = 22 nucleus 32Ne at the newly completed RIKEN Radioactive Ion Beam Factory. A single γ-ray line with an energy of 722(9) keV was observed in both inelastic scattering of a 226 MeV=u 32Ne beam on a carbon target and proton removal from 33Na at 245 MeV=u. This transition is assigned to the deexcitation of the first Jπ = 2+ state in 32Ne to the 0+ ground state. Interpreted through comparison with state-of-the-art shell-model calculations, the low excitation energy demonstrates that the ‘‘island of inversion’’ extends to at least N = 22 for the Ne isotopes.
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- Aghion, S., et al.
(författare)
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A moiré deflectometer for antimatter
- 2014
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The precise measurement of forces is one way to obtain deep insight into the fundamental interactions present in nature. In the context of neutral antimatter, the gravitational interaction is of high interest, potentially revealing new forces that violate the weak equivalence principle. Here we report on a successful extension of a tool from atom optics—the moiré deflectometer—for a measurement of the acceleration of slow antiprotons. The setup consists of two identical transmission gratings and a spatially resolving emulsion detector for antiproton annihilations. Absolute referencing of the observed antimatter pattern with a photon pattern experiencing no deflection allows the direct inference of forces present. The concept is also straightforwardly applicable to antihydrogen measurements as pursued by the AEgIS collaboration. The combination of these very different techniques from high energy and atomic physics opens a very promising route to the direct detection of the gravitational acceleration of neutral antimatter.
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- Ariga, T., et al.
(författare)
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Measuring GBAR with emulsion detector
- 2014
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Ingår i: International Journal of Modern Physics, Conference Series. - : World Scientific. - 2010-1945. ; 30
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Tidskriftsartikel (refereegranskat)
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- Inoue T, T, et al.
(författare)
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Autofluorescence imaging videoendoscopy in the diagnosis of chronic atrophic fundal gastritis
- 2010
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Ingår i: Journal of Gastroenterology. - : Springer Science and Business Media LLC. - 0944-1174 .- 1435-5922. ; 45:1, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Diagnosis of chronic atrophic fundal gastritis (CAFG) is important to understand the pathogenesis of gastric diseases and assess the risk of gastric cancer. Autofluorescence imaging videoendoscopy (AFI) may enable the detection of mucosal features not apparent by conventional white-light endoscopy. The purpose of this study was to estimate the diagnostic ability of AFI in CAFG. Methods: A total of 77 patients were enrolled. Images of the gastric body in AFI and white-light mode were taken to assess the extent of gastritis, and biopsies were taken from green (n = 119) and purple (n = 146) mucosa in AFI images. The diagnostic accuracy of green mucosa for CAFG was investigated according to the Sydney system. Results: In per-patient analysis, the accuracy of green mucosa in patients with activity, inflammation, atrophy and intestinal metaplasia was 64, 93, 88 and 81%, respectively. In per-biopsy analysis, the accuracy for activity, inflammation, atrophy and intestinal metaplasia was 55, 62, 76 and 76%, respectively. Green areas in the gastric body exhibited more inflammation (p\0.001), atrophy (p\0.001) and intestinal metaplasia (p\0.001), whereas purple areas rarely contained atrophy or intestinal metaplasia. The kappa statistics for inter- and intra-observer agreement of AFI on assessing the extent of CAFG were 0.66 and 0.47, while those for white-light endoscopy were 0.56 and 0.39. Conclusions: AFI could diagnose the extent of CAFG as a green area in the gastric body, with higher reproducibility compared with white-light endoscopy. Therefore, AFI may be a useful adjunct to endoscopy to identify patients at high risk of developing gastric cancer.
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