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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. |
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| 4. |
- 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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| 5. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 6. |
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| 7. |
- Bouyoucef, S E, et al.
(författare)
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Poster Session 2 : Monday 4 May 2015, 08
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 15. |
- Katayama, S, et al.
(författare)
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Antisense transcription in the mammalian transcriptome
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1564-1566
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Tidskriftsartikel (refereegranskat)abstract
- Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring “genes” in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.
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| 16. |
- Ohshima, M., et al.
(författare)
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TGF-beta Signaling in Gingival Fibroblast-Epithelial Interaction
- 2010
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Ingår i: Journal of Dental Research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 89:11, s. 1315-1321
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Tidskriftsartikel (refereegranskat)abstract
- The underlying mechanism and the therapeutic regimen for the transition of reversible gingivitis to irreversible periodontitis are unclear. Since transforming growth factor (TGF)-beta has been implicated in differentially regulated gene expression in gingival fibroblasts, we hypothesized that TGF-beta signaling is activated in periodontitis-affected gingiva, along with enhanced collagen degradation, that is reversed by TGF-beta inhibition. A novel three-dimensional (3D) gel-culture system consisting of primary human gingival fibroblasts (GF) and gingival epithelial (GE) cells in collagen gels was applied. GF populations from patients with severe periodontitis degraded collagen gels, which was reduced by TGF-beta-receptor kinase inhibition. Up-regulation of TGF-beta-responsive genes was evident in GF/GE cocultures. Furthermore, the TGF-beta downstream transducer Smad3C was highly phosphorylated in periodontitis-affected gingiva and 3D cultures. These results imply that TGF-beta signaling is involved in fibroblast-epithelial cell interaction in periodontitis, and suggest that the 3D culture system is a useful in vitro model for therapeutic drug screening for periodontitis.
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| 19. |
- Srikulnath, K., et al.
(författare)
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Identification of the linkage group of the Z sex chromosomes of the sand lizard (Lacerta agilis, Lacertidae) and elucidation of karyotype evolution in lacertid lizards
- 2014
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Ingår i: Chromosoma. - : Springer Science and Business Media LLC. - 0009-5915 .- 1432-0886. ; 123:6, s. 563-575
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Tidskriftsartikel (refereegranskat)abstract
- The sand lizard (Lacerta agilis, Lacertidae) has a chromosome number of 2n = 38, with 17 pairs of acrocentric chromosomes, one pair of microchromosomes, a large acrocentric Z chromosome, and a micro-W chromosome. To investigate the process of karyotype evolution in L. agilis, we performed chromosome banding and fluorescent in situ hybridization for gene mapping and constructed a cytogenetic map with 86 functional genes. Chromosome banding revealed that the Z chromosome is the fifth largest chromosome. The cytogenetic map revealed homology of the L. agilis Z chromosome with chicken chromosomes 6 and 9. Comparison of the L. agilis cytogenetic map with those of four Toxicofera species with many microchromosomes (Elaphe quadrivirgata, Varanus salvator macromaculatus, Leiolepis reevesii rubritaeniata, and Anolis carolinensis) showed highly conserved linkage homology of L. agilis chromosomes (LAG) 1, 2, 3, 4, 5(Z), 7, 8, 9, and 10 with macrochromosomes and/or macrochromosome segments of the four Toxicofera species. Most of the genes located on the microchromosomes of Toxicofera were localized to LAG6, small acrocentric chromosomes (LAG11-18), and a microchromosome (LAG19) in L. agilis. These results suggest that the L. agilis karyotype resulted from frequent fusions of microchromosomes, which occurred in the ancestral karyotype of Toxicofera and led to the disappearance of microchromosomes and the appearance of many small macrochromosomes.
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| 20. |
- Zhang, Shidong, et al.
(författare)
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Simple and complex polymer electrolyte fuel cell stack models : A comparison
- 2018. - 13
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Ingår i: ECS Transactions. - : The Electrochemical Society. - 1938-6737 .- 1938-5862. - 9781607685395 ; 86, s. 287-300
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Konferensbidrag (refereegranskat)abstract
- In this paper, two distinct polymer electrolyte fuel cell stack models are constructed: a detailed numerical model (DNM) employing a fine-scale computational mesh and a coarse-mesh approach based on a distributed resistance analogy (DRA) where diffusion terms in the transport equations are replaced by rate terms. Both methods are applied to a 5-cell, high-temperature polymer electrolyte fuel cell stack with an active area of 200 cm2 per cell. The polarization curve and local current density distributions from both the DRA and DNM are compared with experimental data, finding good agreement. Temperature, pressure, Nernst potential, and species distributions are also exhibited. The DNM displays details of fine-scale local extrema not captured by the DRA; however, the latter requires orders of magnitude less computer processor power and memory for execution. Both methods provide much finer-scale results than present experimental techniques.
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| 21. |
- Craig, O. E., et al.
(författare)
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Earliest evidence for the use of pottery
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 496:7445, s. 351-354
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Tidskriftsartikel (refereegranskat)abstract
- Pottery was a hunter-gatherer innovation that first emerged in East Asia between 20,000 and 12,000 calibrated years before present(1,2) (cal BP), towards the end of the Late Pleistocene epoch, a period of time when humans were adjusting to changing climates and new environments. Ceramic container technologies were one of a range of late glacial adaptations that were pivotal to structuring subsequent cultural trajectories in different regions of the world, but the reasons for their emergence and widespread uptake are poorly understood. The first ceramic containers must have provided prehistoric hunter-gatherers with attractive new strategies for processing and consuming foodstuffs, but virtually nothing is known of how early pots were used. Here we report the chemical analysis of food residues associated with Late Pleistocene pottery, focusing on one of the best-studied prehistoric ceramic sequences in the world, the Japanese Jomon. We demonstrate that lipids can be recovered reliably from charred surface deposits adhering to pottery dating from about 15,000 to 11,800 cal BP (the Incipient Jomon period), the oldest pottery so far investigated, and that in most cases these organic compounds are unequivocally derived from processing freshwater and marine organisms. Stable isotope data support the lipid evidence and suggest that most of the 101 charred deposits analysed, from across the major islands of Japan, were derived from high-trophic-level aquatic food. Productive aquatic ecotones were heavily exploited by late glacial foragers(3), perhaps providing an initial impetus for investment in ceramic container technology, and paving the way for further intensification of pottery use by hunter-gatherers in the early Holocene epoch. Now that we have shown that it is possible to analyse organic residues from some of the world's earliest ceramic vessels, the subsequent development of this critical technology can be clarified through further widespread testing of hunter-gatherer pottery from later periods.
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| 22. |
- Horvath, Alexandra, et al.
(författare)
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Objectifying the Pivot Shift Test
- 2020
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Ingår i: Sports medicine and arthroscopy review. - 1538-1951. ; 28:2, s. 36-40
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Tidskriftsartikel (refereegranskat)abstract
- The pivot shift test is utilized for assessment of rotatory instability in the anterior cruciate ligament (ACL) deficient knee. There are multiple reports of the pivot shift maneuver, and there is a lack of consensus among clinicians as to a standardized maneuver. Measurement devices are a feasible option to evaluate rotatory knee instability, objectively or quantitatively. Traditionally, measurement systems have been invasive systems. More recently, electromagnetic system, inertial sensor, or imaging analysis systems, specifically with the utilization of a tablet computer, have emerged as noninvasive, and more importantly, validated options. It is important to recognize that anatomic structures other than the ACL contribute to rotatory knee stability. Addressing the tibial slope, anterolateral structures of the knee, specifically the iliotibial band, and menisci during ACL surgery may decrease residual pivot shift in an attempt to improve clinical outcomes and prevent reinjury. This review article describes the pivot shift maneuver, objective measurement tools, and clinical applications of the pivot shift test.
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| 23. |
- Nishida, Y, et al.
(författare)
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MRI measurements of orbital tissues in dysthyroid ophthalmopathy
- 2001
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Ingår i: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. - : Springer Science and Business Media LLC. - 0721-832X. ; 239:11, s. 824-831
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Tidskriftsartikel (refereegranskat)
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