高齢者における感染症治療の個別最適化を目指したクリニカルファーマコメトリクスの実践 : 抗菌薬適正使用による薬剤耐性対策へ向けて

内容の要約広島大学(Hiroshima University)博士(薬学)Doctor of Philosophy in Pharmaceutical Sciencedoctora

Galactic distributions of carbon- and oxygen-rich AGB stars revealed by the AKARI mid-infrared all-sky survey

Context: The environmental conditions for asympotic giant branch (AGB) stars to reach the carbon-rich (C-rich) phase are important to understand the evolutionary process of AGB stars. The difference between the spatial distributions of C-rich and oxygen-rich (O-rich) AGB stars is essential for the study of the Galactic structure and the chemical evolution of the interstellar medium (ISM). Aims: We quantitatively investigate the spatial distributions of C-rich and O-rich AGB stars in our Galaxy. We discuss the difference between them and its origin. Methods: We classify a large number of AGB stars newly detected by the AKARI id-infrared all-sky survey. In the color-color diagrams, we define their occupation zones based on the locations of known objects. We then obtain the spatial distributions of C-rich and O-rich AGB stars, assuming that they have the same luminosity for a given mass-loss rate. Results: We find that O-rich AGB stars are concentrated toward the Galactic center and that the density decreases with Galactocentric distance, whereas C-rich AGB stars show a relatively uniform distribution within about 8kpc of Sun. Conclusion: Our result confirms the trends reported in previous studies and extends them to a Galactic scale. We discuss the relations between our result, the Galactic metallicity gradient, and the chemical evolution of the ISM in our Galaxy.Comment: 13 pages, 24 figures, Accepted for A&

Bundling of collagen fibrils influences osteocyte network formation during bone modeling

Osteocytes form a cellular network by gap junctions between their cell processes. This network is important since intercellular communication via the network is essential for bone metabolism. However, the factors that influence the formation of this osteocyte network remain unknown. As the early stage of osteocyte network formation occurs on the bone surface, we observed a newly formed trabecular bone surface by orthogonal focused ion beam-scanning electron microscopy. The embedding late osteoblast processes tended to avoid bundled collagen fibrils and elongate into sparse collagen fibrils. Then, we examined whether the inhibition of bundling of collagen fibrils using a potent lysyl oxidase inhibitor, beta-aminopropionitrile (BAPN) changed the cellular network of the chick calvaria. The osteocyte shape of the control group was spindle-shape, while that of the BAPN group was sphere-shaped. In addition, the osteocyte processes of the control group were elongated vertically to the long axis of the cell body, whereas the osteocyte processes of the BAPN group were elongated radially. Therefore, it was suggested that the bundling of collagen fibrils influences normal osteocyte network formation during bone modeling

Herbig Ae/Be Stars in the Magellanic Bridge

We have found Herbig Ae/Be star candidates in the western region of the Magellanic Bridge. Using the near infrared camera SIRIUS and the 1.4 m telescope IRSF, we surveyed about 3.0 deg x 1.3 deg (24 deg < RA < 36 deg, -75 deg < Dec. < -73.7 deg) in the J, H, and Ks bands. On the basis of colors and magnitudes, about 200 Herbig Ae/Be star candidates are selected. Considering the contaminations by miscellaneous sources such as foreground stars and early-type dwarfs in the Magellanic Bridge, we estimate that about 80 (about 40%) of the candidates are likely to be Herbig Ae/Be stars. We also found one concentration of the candidates at the young star cluster NGC 796, strongly suggesting the existence of pre-main-sequence (PMS) stars in the Magellanic Bridge. This is the first detection of PMS star candidates in the Magellanic Bridge, and if they are genuine PMS stars, this could be direct evidence of recent star formation. However, the estimate of the number of Herbig Ae/Be stars depends on the fraction of classical Be stars, and thus a more precise determination of the Be star fraction or observations to differentiate between the Herbig Ae/Be stars and classical Be stars are required.Comment: 22 pages, 6 figures. Accepted for publication in Ap

An Active C-Terminally Truncated Form of Ca2+/Calmodulin-Dependent Protein Kinase Phosphatase-N (CaMKP-N/PPM1E)

Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) and its nuclear homolog CaMKP-N (PPM1E) are Ser/Thr protein phosphatases that belong to the PPM family. CaMKP-N is expressed in the brain and undergoes proteolytic processing to yield a C-terminally truncated form. The physiological significance of this processing, however, is not fully understood. Using a wheat-embryo cell-free protein expression system, we prepared human CaMKP-N (hCaMKP-N(WT)) and the truncated form, hCaMKP-N(1–559), to compare their enzymatic properties using a phosphopeptide substrate. The hCaMKP-N(1–559) exhibited a much higher value than the hCaMKP-N(WT) did, suggesting that the processing may be a regulatory mechanism to generate a more active species. The active form, hCaMKP-N(1–559), showed Mn2+ or Mg2+-dependent phosphatase activity with a strong preference for phospho-Thr residues and was severely inhibited by NaF, but not by okadaic acid, calyculin A, or 1-amino-8-naphthol-2,4-disulfonic acid, a specific inhibitor of CaMKP. It could bind to postsynaptic density and dephosphorylate the autophosphorylated Ca2+/calmodulin-dependent protein kinase II. Furthermore, it was inactivated by H2O2 treatment, and the inactivation was completely reversed by treatment with DTT, implying that this process is reversibly regulated by oxidation/reduction. The truncated CaMKP-N may play an important physiological role in neuronal cells.This work was supported, in part, by Grants-in-Aid for Scientific Research (21590334) from the Ministry of Education, Science, Sports, and Culture of Japan and by a grant from the Japan Foundation for Applied Enzymology

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation

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