| 21. |
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| 22. |
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| 23. |
- 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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| 24. |
- Adler, S. S., et al.
(författare)
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High transverse momentum eta meson production in p+p, d+Au, and Au+Au collisions at root s(NN)=200 GeV
- 2007
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 75:2
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Forskningsöversikt (refereegranskat)abstract
- Inclusive transverse momentum spectra of eta mesons in the range p(T)approximate to 2-12 GeV/c have been measured at midrapidity (vertical bar eta vertical bar < 0.35) by the PHENIX experiment at RHIC in p+p,d+Au, and Au+Au collisions at root s(NN)=200 GeV. The eta mesons are reconstructed through their eta ->gamma gamma channel for the three colliding systems as well as through the eta ->pi(0)pi(+)pi(-) decay mode in p+p and d+Au collisions. The nuclear modification factor in d+Au collisions, R-dAu(p(T))approximate to 1.0-1.1, suggests at most only modest p(T) broadening ("Cronin enhancement"). In central Au+Au reactions, the eta yields are significantly suppressed, with R-AuAu(p(T))approximate to 0.2. The ratio of eta to pi(0) yields is approximately constant as a function of p(T) for the three colliding systems in agreement with the high-p(T) world average of R-eta/pi(0)approximate to 0.5 in hadron-hadron, hadron-nucleus, and nucleus-nucleus collisions for a wide range of center-of-mass energies (root sNN approximate to 3-1800 GeV) as well as, for high scaled momentum x(p), in e(+)e(-) annihilations at root s=91.2 GeV. These results are consistent with a scenario where high-p(T) eta production in nuclear collisions at the Relativistic Heavy Ion Collider is largely unaffected by initial-state effects but where light-quark mesons (pi(0),eta) are equally suppressed due to final-state interactions of the parent partons in the dense medium produced in Au+Au reactions.
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| 25. |
- 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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| 26. |
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| 27. |
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| 28. |
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| 29. |
- Adcox, K, et al.
(författare)
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Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX Collaboration
- 2005
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Ingår i: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 757:1-2, s. 184-283
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Forskningsöversikt (refereegranskat)abstract
- Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (PT), elliptic flow, two-particle correlations, nonstatistical fluctuations, and suppression of particle production at high PT. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.
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| 30. |
- Adler, S. S., et al.
(författare)
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Evidence for a long-range component in the pion emission source in Au plus Au collisions at root s(NN)=200 GeV
- 2007
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Ingår i: Physical Review Letters. - 1079-7114. ; 98:13
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Tidskriftsartikel (refereegranskat)abstract
- Emission source functions are extracted from correlation functions constructed from charged pions produced at midrapidity in Au+Au collisions at s(NN)=200 GeV. The source parameters extracted from these functions at low k(T) give first indications of a long tail for the pion emission source. The source extension cannot be explained solely by simple kinematic considerations. The possible role of a halo of secondary pions from resonance emissions is explored.
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