| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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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. |
- 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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| 4. |
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| 5. |
- Mironov, Oleg A., et al.
(författare)
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Using Reduced Catalysts for Oxidation Reactions : Mechanistic Studies of the “Periana-Catalytica” System for CH4 Oxidation
- 2013
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 135:39, s. 14644-14658
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Tidskriftsartikel (refereegranskat)abstract
- Designing oxidation catalysts based on CH activation with reduced, low oxidation state species is a seeming dilemma given the proclivity for catalyst deactivation by overoxidation. This dilemma has been recognized in the Shilov system where reduced Pt-II is used to catalyze methane functionalization. Thus, it is generally accepted that key to replacing Pt-IV in that system with more practical oxidants is ensuring that the oxidant does not over-oxidize the reduced Pt-II species. The “Periana-Catalytica” system, which utilizes (bpym)-(PtCl2)-Cl-II in concentrated sulfuric acid solvent at 200 degrees C, is a highly stable catalyst for the selective, high yield oxy-functionalization of methane. In lieu of the over-oxidation dilemma, the high stability and observed rapid oxidation of (bpym)(PtCl2)-Cl-II to Pt-IV in the absence of methane would seem to contradict the originally proposed mechanism involving CH activation by a reduced Pt-II species. Mechanistic studies show that the originally proposed mechanism is incomplete and that while CH activation does proceed with Pt-II there is a solution to the over oxidation dilemma. Importantly, contrary to the accepted view to minimize Pt-II overoxidation, these studies also show that increasing that rate could increase the rate of catalysis and catalyst stability. The mechanistic basis for this counterintuitive prediction could help to guide the design of new catalysts for alkane oxidation that operate by CH activation.
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| 6. |
- Zeichner, Sarah S., et al.
(författare)
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Polycyclic aromatic hydrocarbons in samples of Ryugu formed in the interstellar medium
- 2023
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Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 382:6677, s. 1411-1415
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Tidskriftsartikel (refereegranskat)abstract
- Polycyclic aromatic hydrocarbons (PAHs) contain less than or similar to 20% of the carbon in the interstellar medium. They are potentially produced in circumstellar environments (at temperatures greater than or similar to 1000 kelvin), by (similar to 10 kelvin) interstellar clouds, or by processing of carbon-rich dust grains. We report isotopic properties of PAHs extracted from samples of the asteroid Ryugu and the meteorite Murchison. The doubly-C-13 substituted compositions (Delta 2x(13)C values) of the PAHs naphthalene, fluoranthene, and pyrene are 9 to 51 parts per thousand higher than values expected for a stochastic distribution of isotopes. The Delta 2x(13)C values are higher than expected if the PAHs formed in a circumstellar environment, but consistent with formation in the interstellar medium. By contrast, the PAHs phenanthrene and anthracene in Ryugu samples have Delta 2x(13)C values consistent with formation by higher-temperature reactions.
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