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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. |
- Bowman, John L, et al.
(författare)
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Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome
- 2017
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 171:2, s. 287-304.15
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP.
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| 5. |
- Cook, Edward R., et al.
(författare)
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Tree-ring reconstructed summer temperature anomalies for temperate East Asia since 800 CE
- 2013
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 41:11-12, s. 2957-2972
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Tidskriftsartikel (refereegranskat)abstract
- We develop a summer temperature reconstruction for temperate East Asia based on a network of annual tree-ring chronologies covering the period 800-1989 C.E. The East Asia reconstruction is the regional average of 585 individual grid point summer temperature reconstructions produced using an ensemble version of point-by-point regression. Statistical calibration and validation tests indicate that the regional average possesses sufficient overall skill to allow it to be used to study the causes of temperature variability and change over the region. The reconstruction suggests a moderately warm early medieval epoch (ca. 850-1050 C.E.), followed by generally cooler 'Little Ice Age' conditions (ca. 1350-1880 C.E.) and 20th century warming up to the present time. Since 1990, average temperature has exceeded past warm epochs of comparable duration, but it is not statistically unprecedented. Superposed epoch analysis reveals a volcanic forcing signal in the East Asia summer temperature reconstruction, resulting in pulses of cooler summer conditions that may persist for several years. Substantial uncertainties remain, however, particularly at lower frequencies, thus requiring caution and scientific prudence in the interpretation of this record.
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| 8. |
- Shi, Feng, et al.
(författare)
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A multi-proxy reconstruction of spatial and temporal variations in Asian summer temperatures over the last millennium
- 2015
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Ingår i: Climatic Change. - : Springer Science and Business Media LLC. - 0165-0009 .- 1573-1480. ; 131:4, s. 663-674
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Tidskriftsartikel (refereegranskat)abstract
- To investigate climate variability in Asia during the last millennium, the spatial and temporal evolution of summer (June–July–August; JJA) temperature in eastern and south-central Asia is reconstructed using multi-proxy records and the regularized expectation maximization (RegEM) algorithm with truncated total least squares (TTLS), under a point-by-point regression (PPR) framework. The temperature index reconstructions show that the late 20th century was the warmest period in Asia over the past millennium. The temperature field reconstructions illustrate that temperatures in central, eastern, and southern China during the 11th and 13th centuries, and in western Asia during the 12th century, were significantly higher than those in other regions, and comparable to levels in the 20th century. Except for the most recent warming, all identified warm events showed distinct regional expressions and none were uniform over the entire reconstruction area. The main finding of the study is that spatial temperature patterns have, on centennial time-scales, varied greatly over the last millennium. Moreover, seven climate model simulations, from the Coupled Model Intercomparison Project Phase 5 (CMIP5), over the same region of Asia, are all consistent with the temperature index reconstruction at the 99 % confidence level. Only spatial temperature patterns extracted as the first empirical orthogonal function (EOF) from the GISS-E2-R and MPI-ESM-P model simulations are significant and consistent with the temperature field reconstruction over the past millennium in Asia at the 90 % confidence level. This indicates that both the reconstruction and the simulations depict the temporal climate variability well over the past millennium. However, the spatial simulation or reconstruction capability of climate variability over the past millennium could be still limited. For reconstruction, some grid points do not pass validation tests and reveal the need for more proxies with high temporal resolution, accurate dating, and sensitive temperature signals, especially in central Asia and before AD 1400.
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| 9. |
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| 10. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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