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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. |
- Lopes, T. S., et al.
(författare)
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Cu(In,Ga)Se2 based ultrathin solar cells the pathway from lab rigid to large scale flexible technology
- 2023
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Ingår i: npj Flexible Electronics. - : Springer Nature. - 2397-4621. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The incorporation of interface passivation structures in ultrathin Cu(In,Ga)Se2 based solar cells is shown. The fabrication used an industry scalable lithography technique—nanoimprint lithography (NIL)—for a 15 × 15 cm2 dielectric layer patterning. Devices with a NIL nanopatterned dielectric layer are benchmarked against electron-beam lithography (EBL) patterning, using rigid substrates. The NIL patterned device shows similar performance to the EBL patterned device.The impact of the lithographic processes in the rigid solar cells’ performance were evaluated via X-ray Photoelectron Spectroscopy and through a Solar Cell Capacitance Simulator. The device on stainless-steel showed a slightly lower performance than the rigid approach, due to additional challenges of processing steel substrates, even though scanning transmission electron microscopy did not show clear evidence of impurity diffusion. Notwithstanding, time-resolved photoluminescence results strongly suggested elemental diffusion from the flexible substrate. Nevertheless, bending tests on the stainless-steel device demonstrated the mechanical stability of the CIGS-based device.
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| 5. |
- Martinez-Gonzalez, I, et al.
(författare)
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New insights into ILC2 memory
- 2024
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Ingår i: Immunological reviews. - 1600-065X. ; 323:1, s. 118-125
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Matha, L, et al.
(författare)
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The Fate of Activated Group 2 Innate Lymphoid Cells
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 671966-
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Tidskriftsartikel (refereegranskat)abstract
- Group 2 innate lymphoid cells (ILC2s) reside in both mucosal and non-mucosal tissues and play critical roles in the first line of defense against parasites and irritants such as allergens. Upon activation by cytokines released from epithelial and stromal cells during tissue damage or stimulation, ILC2s produce copious amounts of IL-5 and IL-13, leading to type 2 inflammation. Over the past 10 years, ILC2 involvement in a variety of human diseases has been unveiled. However, questions remain as to the fate of ILC2s after activation and how that might impact their role in chronic inflammatory diseases such as asthma and fibrosis. Here, we review studies that have revealed novel properties of post-activation ILC2s including the generation of immunological memory, exhausted-like phenotype, transdifferentiation and activation-induced migration.
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| 7. |
- Mathae, L, et al.
(författare)
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Tissue Resident and Migratory Group 2 Innate Lymphoid Cells
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 877005-
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Tidskriftsartikel (refereegranskat)abstract
- Group 2 innate lymphoid cells (ILC2s) are present in both mouse and human mucosal and non-mucosal tissues and implicated in initiating type 2 inflammation. ILC2s are considered to be tissue resident cells that develop in the perinatal period and persist throughout life with minimal turning over in adulthood. However, recent studies in animal models have shown their ability to circulate between different organs during inflammation and their potential functions in the destined organs, suggesting their roles in mediating multiple type 2 diseases. Here, we review recent findings on ILC2 migration, including migration within, into and out of tissues during inflammation.
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| 9. |
- Sumpter, N. A., et al.
(författare)
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Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout
- 2023
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:5, s. 816-825
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout. Methods. A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease. Results. The PRS was associated with earlier age at gout onset in men (beta = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; beta = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; beta = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (beta = 0.07 [95% CI -2.32, 2.45] in European women; beta = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; beta -3.33 [95% CI -9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (beta = -2.42 [95% CI -3.37, -1.46] and beta = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (beta = -1.79 [95% CI -4.74, 1.16]). Conclusion. Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.
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