成人骨髄におけるCXCL12-abundant reticular 細胞の同定

京都大学新制・論文博士博士(医学)乙第13441号論医博第2240号新制||医||1054(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 生田 宏一, 教授 滝田 順子, 教授 江藤 浩之学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDFA

MHD Modeling for Formation Process of Coronal Mass Ejections: Interaction between Ejecting Flux Rope and Ambient Field

We performed magnetohydrodynamic simulation of a formation process of coronal mass ejections (CMEs), focusing on interaction (reconnection) between an ejecting flux rope and its ambient field. We examined three cases with different ambient fields: no ambient field, and cases with dipole field of two opposite directions which are parallel and anti-parallel to that of the flux rope surface. As a result, while the flux rope disappears in the anti-parallel case, in other cases the flux ropes can evolve to CMEs and show different amounts of rotation of the flux rope. The results imply that the interaction between an ejecting flux rope and its ambient field is an important process for determining CME formation and CME orientation, and also show that the amount and direction of magnetic flux within the flux rope and the ambient field are key parameters for CME formation. Especially, the interaction (reconnection) plays a significant role to the rotation of the flux rope, with a process similar to "tilting instability" in a spheromak-type experiment of laboratory plasma.Comment: 24 pages, 5 figures. Accepted for publication in Ap

Clinical impact of the loss of chromosome 7q on outcomes of patients with myelodysplastic syndromes treated with allogeneic hematopoietic stem cell transplantation

We conducted a nationwide retrospective study to evaluate the prognostic influence of +1, der(1;7)(q10;p10) [hereafter der(1;7)] and ?7/del(7q) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for de novo myelodysplastic syndromes (MDS). In this database, 69 MDS patients with der(1;7), 75 with ?7/del(7q), and 511 with normal karyotype (NK) underwent allo-HSCT at advanced disease status. The 3-year overall survival (OS) and cumulative incidence of relapse (CIR) were 50.4 and 19.4% for those with der(1;7), 36.2 and 38.4% for ?7/del(7q),and 51.1 and 20.7% for NK, respectively. In the multivariate analysis, the presence of ?7/del(7q) correlated with a significantly shorter OS (HR [95% CI], 1.38 [1.00?1.89]; P = 0.048) and higher CIR (HR, 2.11 [1.36?3.28]; P = 0.001) than those with NK. There were 23 patients with der(1;7), 29 with ?7/del(7q), and 347 with NK who underwent allo-HSCT at early disease status.The 3-year OS and CIR were as follows: 47.3 and 9.5% for the der(1;7) group, 70.5 and 13.8% for ?7/del(7q), and 70.9 and 5.6% for NK,respectively. No significant differences were observed in OS and CIR among three groups. The impact of the loss of chromosome 7q on OS and CIR may differ based on its type and disease status after allo-HSCT for MDS

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. 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

Site fidelity, ontogenetic shift and diet composition of green turtles Chelonia mydas in Japan inferred from stable isotope analysis

Incomplete knowledge about local foraging ecology of green turtles hampers their conservation management in Japan, where stocks have only partially recovered from heavy exploitation in previous centuries. We used stable isotope ratios of δ13C and δ15N for turtle carapace scutes, where successive layers contain a chronological record of diet assimilated over a period of years. Turtles were sampled at 2 geographically separate foraging grounds in Japan: the temperate Main Islands (n = 32) and the sub-tropical Nansei Islands (n = 42). Site fidelity was inferred for the majority of turtles at each site (81 and 64% resident turtles) because isotope data indicated diets consistent with food taxa at the respective sites. Immigrant turtles (previous diet outside their current site) were few (n = 4) at the Main Islands site but numerous (n = 14) at the Nansei Islands site, where they were significantly smaller than residents. An ontogenetic shift (Main Islands to Nansei Islands) was inferred for many of the immigrants on the basis of isotope evidence and body size. These immigrants corresponded to a size cohort that was relatively scarce in Main Islands foraging grounds according to previous studies. Bayesian mixing models, used to estimate proportional components of diet, showed varying degrees of imbalance between seagrass and algae and indicated that hypothetical consumption of non-trivial amounts of animal matter was plausible. The latter represented a hypothetical diet component for study turtles since animal matter was rarely found in stomach contents. Potential ambiguity and other issues that constrained inference from mixing models are discussed