『古事記』における〈古〉の世界

学位の種別: 論文博士審査委員会委員 : （主査）東京大学講師 徳盛 誠, 東京大学教授 菅原 克也, 東京大学教授 桜井 英治, 東京大学名誉教授 神野志 隆光, 早稲田大学教授 松本 直樹University of Tokyo(東京大学

A new bioactive cembranoid sarcophytonolide V from Bornean soft coral genus Sarcophyton

A new cembranolide diterpene, sarcophytonolide V (1), along with 6 known compounds, isosarcophytonolide D (2), (4Z,8S*,9R*,12E,14E) -9-hydroxy-1- (prop-1-en-2-yl) -8,12- dimethyl- oxabicyclo[9.3.2]-hexadeca-4,12,14-trien-18-one (3), (7E,11E)-3,4-epoxy-7,11, 15- cembratriene (4), (1S*,3S*,4S*,7E,11E)-3,4-epoxy-13-oxo-7,11,15-cembratriene (5), (-) -eunicenone (6), and 2-[(E,E,E)-7′, 8′-epoxy-4′,8′,12′ -trimethylcyclotetradeca- 1′,3′,11′- trienyl] propan-2-ol (7) were isolated from the Bornean soft coral Sarcophyton sp. Their structures were elucidated based on spectroscopic data, such as nuclear magnetic resonance (NMR) and high resolution electron spray ionization mass spectroscopy (HRESIMS). These compounds were evaluated for their biological activity against marine pathogenic fungi

The Chemotaxonomic Identification Using Structure Types of Secondary Metabolites and Their Bioactivities of Bornean Litophyton arboretum

The structure types and bioactivities of secondary metabolites derived from Litophyton arboreum, distributed in Sepanggar Bay, Sabah, Malaysia, were investigated as additional tools for establishing their species identification. As a result, a total of two secondary metabolites (alismol (1) and 10α-methoxy-4βhydroxy guaian-6-ene (2)) were isolated from Bornean soft coral L. arboreum. Their structures were elucidated based on spectroscopic data analysis and the antifungal activities of compounds 1 and 2 were determined. In addition, the compound 2 showed highest antifungal activity against Haliphthoros milfordensis. As a result of comparison with previous literature, significant variations were observed in relation to structure types of secondary metabolites and bioactivities. Information from this study gives additional evidence of chemotaxonomic significance and baseline data for effective selection of suitable lead pharmaceuticals

Phillipsins A and B from Zingiber phillippsii Mood & Theilade in Borneo

Two new aromatic compounds, phillipsins A (1) and B (2) were isolated from the Bornean wild ginger Zingiber phillippsii Mood & Theilade, and were characterized based on spectroscopic data (HRESI-MS, FTIR as well as 1D and 2D NMR). These metabolites also exhibited strong antifungal activity against selected fungi

Novel acyclic diterpeneoid from Bornean local red Chilli pepper Capsicum frutescens L.

An unknown acyclic diterpene (3S, 6E, 10E, 14Z)-3-hydroxy-3,7,11,15-tetramethyl-1,6,10,14- hexadecatetraene acid (1) along with four known secondary metabolites (3S, 6E, 10E, 14Z)-20- hydroxygeranyllinalool (2), trans-capsaicin (3), nordihydrocapsaicin (4) and capsidiol (5) were isolated from the Bornean red chilli pepper Capsicum frutescens L. The structures of the secondary metabolites were determined based on spectroscopic data analysis such as NMR, HRESIMS, and IR data. The new compound 1 is a carboxylic acid precursor that would condensate with vanillylamine in the phenylpropanoid pathway in the biosynthesis of capsaicinoids. Discovery of this compound is an important milestone in our understanding of the capsaicinoids biosynthesis

Antiparasitic potential of chromatographic fractions of nephrolepis biserrata and liquid chromatography-quadrupole time-of-flight-mass spectrometry analysis

Marine aquaculture development is recently impeded by parasitic leech Zeylanicobdella arugamensis (Hirudinea, Piscicolidae) in Sabah, Malaysia. The parasitic leech infests a variety of cultured fishes in aquaculture facilities. In this study, we evaluated the antiparasitic activity of the chromatographic fractions of the medicinal plant Nephrolepis biserrata methanol extract against Z. arugamensis and highlighted the potential metabolites responsible for the antiparasitic properties through liquid chromatography (LC)–quadrupole time-of-flight (QTOF)–mass spectrometry (MS) analysis. Out of seven fractions obtained through flash column chromatography techniques, three fractions demonstrated antiparasitic properties. Significant parasitic mortality was indicated by fraction 3 at a concentration of 2.50 mg/mL, all the leeches were killed in a time limit of 1.92 ± 0.59 min. followed by fraction 4 (14 mg/mL) in 34.57 ± 3.39 and fraction 5 (15.3 mg/mL) in 36.82 ± 4.53 min. LC-QTOF-MS analysis indicated the presence of secondary metabolites including phytosphingosine (6), pyrethrosin (1), haplophytine (9), ivalin (2), warburganal (3), isodomedin (4) and pheophorbide a (16), representing sphingoid, alkaloid, terpenoid, phenolic and flavonoid groups. Thus, our study indicated that the chromatographic fractions of N. biserrata demonstrated significant antiparasitic activity against the marine parasitic leeches due to the presence of potent antiparasitic bioactive compounds

Access to mechanical thrombectomy and ischemic stroke mortality in Japan: a spatial ecological study

BackgroundAdvances in stroke treatment have greatly improved outcomes; however, disparities in access to treatment might increase. Achieving equitable access to stroke treatment is a health policy challenge, as rapid treatment is essential for positive outcomes. This ecological cross-sectional study aimed to determine the relationship between the disparities in spatial accessibility to mechanical thrombectomy (SAMT) and stroke mortality rates in Japan, hypothesizing that disparities in SAMT may increase the differences in stroke mortality between regions.MethodsWe used the average number of ischemic stroke (IS) deaths between 2020 and 2021 as the response variable; and SAMT, medical resources, and socioeconomic characteristics of each municipality as explanatory variables. A conditional autoregressive model was used to examine the association between the risk of stroke mortality and SAMT. The standardized mortality ratio (SMR) was mapped to understand the nationwide disparities in stroke mortality risk.ResultsThe median number of IS deaths was 17.5 persons per year in the municipalities (2020 to 2021). The study also found that municipalities with low SAMT were located in the northern part of Japan. The non-spatial regression model results indicated that poor accessibility, a small proportion of bachelor’s degrees or higher, and a high proportion of workers in secondary industries were related to high IS mortality. Three models were evaluated using spatial analysis; Model 1 with accessibility indicators alone, Model 2 with medical resources added to Model 1, and Model 3 with socioeconomic characteristics added to Model 2. In Models 1 and 2, the population-weighted spatial accessibility index (PWSAI) showed a significant negative relationship with stroke mortality. However, this was not evident in Model 3. Mapping using Model 3 showed that the high-risk areas were predominantly located in northern Japan, excluding Hokkaido.ConclusionAccess to mechanical thrombectomy was estimated, and regional differences were observed. The relationship between accessibility and IS mortality is unknown; however, regardless of accessibility, municipalities with a high proportion of workers in secondary industries and a small proportion with bachelor’s degrees or above are at risk of death from stroke

High-resolution chemical profiling and antiparasitic potential of the tropical shrub Dillenia suffruticosa

The aquaculture industry is growing rapidly throughout the world, but due to intensifcation, fsh hatcheries are often faced with infestations of parasites, which can lead to economic loss. Among these parasites, the leech Zeylanicobdella arugamensis (Hirudinea: Piscicolidae) has been reported to impact hybrid groupers and other hosts. The objective of this study was to test the antiparasitic potential of chromatographic fractions of a crude methanolic extract of the tropical shrub Dillenia sufruticosa. The phytochemical composition of the shrub was determined using high-resolution liquid chromatography (LC)–quadrupole time-of-fight (QTOF)–mass spectrometry (MS) to narrow down the metabolites responsible for its antiparasitic properties. Seven fractions of a methanolic extract of D. sufruticosa were obtained through fash column chromatography. Various concentrations of the fractions were prepared and tested against Z. arugamensis. In the bioassay conducted with fresh leeches, signifcant mortality was induced by fraction 6 at 31.66±4.88 min, followed by fraction 5 (39.58±2.94 min), fraction 3 (63.75±6.61 min) and fraction 4 (65.25±4.98 min). Chemical profling using LC–QTOF–MS identifed 17 secondary metabolites comprising triterpenoids, sterols, favones, a glycoside, a non-favone phenolid, a pyrrolizine, a fatty acid and a fatty amide. Thus, our study indicated that the D. sufruticosa fractions contained potent bioactive compounds with antiparasitic potential

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.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