| 1. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 2. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Namkoong, H, et al.
(författare)
-
DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
-
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.
|
|
| 7. |
|
|
| 8. |
- Wang, QBS, et al.
(författare)
-
The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
-
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.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Parra, M. A., et al.
(författare)
-
Biomarkers for dementia in Latin American countries: Gaps and opportunities
- 2023
-
Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:2, s. 721-735
-
Tidskriftsartikel (refereegranskat)abstract
- Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Altman, S, et al.
(författare)
-
Cleavage of RNA by RNase P from E. coli
- 1987
-
Ingår i: Molecular Biology of RNA: New Perspectives. - : Academic Press.
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 17. |
- Hasegawa, H., et al.
(författare)
-
Retreat and reformation of X-line during quasi-continuous tailward-of-the-cusp reconnection under northward IMF
- 2008
-
Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 35:15, s. L15104-
-
Tidskriftsartikel (refereegranskat)abstract
- We present observations on 19-20 November 2006 by the Cluster spacecraft that were skimming the high-latitude dusk-flank magnetopause, which are consistent with more than one reconnection X-line present on the tailward side of the cusp under northward IMF. Evidence of quasi-continuous reconnection over 16 hours exists in the form of Alfvenic acceleration of magnetosheath ions found almost always when either of the satellites traversed the boundary. The data indicate that a dominant X-line was sunward of Cluster for most of the time, but ion velocity distributions consisting of two magnetosheath populations demonstrate that for part of the time, more than one X-line existed. Further, the motion of reconnected field lines shows that some X-line(s) retreated tailward. It is inferred that following the X-line retreat, another X-line reformed sunward of Cluster, leading tomultiple X-lines.
|
|
| 18. |
- Helfricht, A, et al.
(författare)
-
Loss of ZBTB24 impairs nonhomologous end-joining and class-switch recombination in patients with ICF syndrome
- 2020
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:11
-
Tidskriftsartikel (refereegranskat)abstract
- The autosomal recessive immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a genetically heterogeneous disorder. Despite the identification of the underlying gene defects, it is unclear how mutations in any of the four known ICF genes cause a primary immunodeficiency. Here we demonstrate that loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance. Mechanistically, we found that ZBTB24 associates with poly(ADP-ribose) polymerase 1 (PARP1) and stimulates its auto-poly(ADP-ribosyl)ation. The zinc-finger in ZBTB24 binds PARP1-associated poly(ADP-ribose) chains and mediates the PARP1-dependent recruitment of ZBTB24 to DNA breaks. Moreover, through its association with poly(ADP-ribose) chains, ZBTB24 protects them from degradation by poly(ADP-ribose) glycohydrolase (PARG). This facilitates the poly(ADP-ribose)-dependent assembly of the LIG4/XRCC4 complex at DNA breaks, thereby promoting error-free NHEJ. Thus, we uncover ZBTB24 as a regulator of PARP1-dependent NHEJ and class-switch recombination, providing a molecular basis for the immunodeficiency in ICF2 syndrome.
|
|
| 19. |
- Inagaki-Kawata, Y, et al.
(författare)
-
Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants
- 2020
-
Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 578-
-
Tidskriftsartikel (refereegranskat)abstract
- The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Keika, K., et al.
(författare)
-
Response of the inner magnetosphere and the plasma sheet to a sudden impulse
- 2008
-
Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 113:A7, s. A07S35-
-
Tidskriftsartikel (refereegranskat)abstract
- [1] The passage of an interplanetary shock caused a sudden compression of the magnetosphere between 0900 UT and 0915 UT on 24 August 2005. An estimate of the shock normal from solar wind data obtained by Geotail upstream of the bow shock indicates symmetric compression with respect to the noon-midnight meridian. Compression-related disturbances of the magnetic and electric field and plasma motion were observed by Double Star Program (DSP) Tan Ce 1 (TC1) and Tan Ce 2 (TC2) in the inner magnetosphere and by the Cluster spacecraft in the dawnside plasma sheet. DSP/TC1 and TC2 observations suggest that the disturbances in the inner magnetosphere are propagating from the dayside magnetopause. Cluster S/C 4 observations indicate that the front normal of the disturbances in the dawnside plasma sheet is phi similar to 180 degrees at 0902: 50 UT and phi = 107 degrees at 0904: 34 UT, where phi is the longitude in GSM coordinates, if we assume that the measured electric field is on the front plane and the normal lies on the X-Y plane. The timing analysis applied to magnetic field data from the four Cluster spacecraft independently gives a front normal, which is calculated to be phi =131 degrees at about 0904: 20 UT. Shock-associated magnetic and electric field disturbances propagating from both the dayside and flank magnetopauses are detected in the plasma sheet; the latter makes the dominant contribution. Substorms are, however, not triggered at the passage of the disturbances.
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
