| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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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. |
- Yarime, Masaru, et al.
(författare)
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Dissipation and Recycling: What Losses, What Dissipation Impacts, and What Recycling Options?
- 2014
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Ingår i: Sustainable Phosphorus Management. - Dordrecht : Springer Netherlands. - 9789400772496 ; , s. 247-274
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter describes the activities in the Dissipation and Recycling Node of Global TraPs, a multistakeholder project on the sustainable management of the global phosphorus (P) cycle. Along the P supply and demand chain, substantial amounts are lost, notably in mining, processing, agriculture via soil erosion, food waste, manure, and sewage sludge. They are not only critical with respect to wasting an essential resource, but also contribute to severe environmental impacts such as eutrophication of freshwater ecosystems or the development of dead zones in oceans. The Recycling and Dissipation Node covers the phosphorus system from those points where phosphate-containing waste or losses have occurred or been produced by human excreta, livestock, and industries. This chapter describes losses and recycling efforts, identifies knowledge implementation and dissemination gaps as well as critical questions, and outlines potential transdisciplinary case studies. Two pathways toward sustainable P management are in focus: To a major goal of sustainable P management therefore must be to (1) quantify P stocks and flows in order to (2) identify key areas for minimizing losses and realizing recycling opportunities. Several technologies already exist to recycle P from different sources, including manure, food waste, sewage, and steelmaking slag; however, due to various factors such as lacking economic incentives, insufficient regulations, technical obstacles, and missing anticipation of unintended impacts, only a minor part of potential secondary P resources has been utilized. Minimizing losses and increasing recycling rates as well as reducing unintended environmental impacts triggered by P dissipation require a better understanding of the social, technological, and economic rationale as well as the intrinsic interrelations between nutrient cycling and ecosystem stability. A useful approach will be to develop new social business models integrating innovative technologies, corporate strategies, and public policies. That requires intensive collaboration between different scientific disciplines and, most importantly, among a variety of key stakeholders, including industry, farmers, and government agencies.
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