Biotransformation of organic compounds in vivo using larvae of beetles (Allomyrina dichotoma) as biocatalysts

The biotransformation of organic compounds using the larvae of the Japanese rhinoceros beetle (Allomyrina dichotoma) as a biocatalyst is described. When phenyl alkanediones were administered by mouth (p.o) or subcutaneous injection (s.c) to the beetle, asymmetric reduction occurred to yield the corresponding diols in varying optical yields: 1-phenyl-1,2-propandione or 1-phenyl-1,3-butanedione reduced to (1R,2S)- and (1S,2S)-1,2-phenylpropanediols in high optical yields or (1R,3S)- and (1R,3R)-1-phenyl-1,3-butanediols in low to high optical yields, respectively. By administrating 1-phenyl-1-propanone, 1-phenyl-1-butanone or 4-phenyl-2-butanone, redox reactions occurred to give 1-phenyl-1,2-propanediols or 1-phenyl-1,3-butanediols in lower optical yields. The administrations of β-ionone and cinnamyl chloride resulted in regioselective allylic oxidations producing enone and cinnamic acid, respectively. However, when (R)-(-)-carvone was administered, regiospecific dihydroxylation at the isopropenyl group occurred to give (4R,8R)- and (4R,8S)-8,9-dihydroxy-8,9-dihydrocarvone as diastereoisomers. These results appear to demonstrate similar reaction tendency with the case of a microorganism. It is possible that these reactions were due in part to bacteria in the intestine of the larva: however, regio- and stereoselectivities of the reactions were sometimes unique. Thus, it is supposed that these biotransformations were accomplished by the ensemble of the larva׳s own enzymes with several bacteria. The results obtained in this study might show the possibility of using such enzymes derived from insects, including beetle larvae, as a biocatalyst

Concentrations and size distributions of black carbon in the surface snow of Eastern Antarctica in 2011

The Tenth Symposium on Polar Science/Ordinary sessions: [OM] Polar Meteorology and Glaciology, Thu. 5 Dec. / 2F Auditorium , National Institute of Polar Researc

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

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

Effects of climate on the radial growth of tree species in the upper and lower distribution limits of an altitudinal ecotone on Mount Norikura, central Japan

The original publication is available at www.springerlink.com.ArticleECOLOGICAL RESEARCH.18(5):549-558(2003)journal articl

A new experimental procedure for evaluating the biological effect of radon

Inhalation of radon and its short-lived progeny gives a considerable amount of radiation dose to the general public. The dosimetry for the radon risk estimation has been attempted by comparing the cancer incidence between different populations including underground miners but not yet suffi ciently accurate to provide quantitative estimates of risks of the radon inhalation. To understand the molecular basis for the lifetime cancer risk caused by the internally deposited radionuclides, especially the alpha particle- emitting nuclides, we planned to establish a simple experimental system using mammary cultured cells. We used mouse FM3A cells, derived from mammary grand tumor cells, that grow on soft agar plates with the plating effi ciency of >90%. Since the cells can grow while being exposed to the atmosphere, we thought it could be an ideal model system to examine the biological effect of radon on epithelial cells. As a preliminary experiment, exponentially growing FM3A cells were exposed to X ray (0, 0.3, 1, 3, and 10Gy), and plated on the medium containing soft-agar. Colonies formed on the soft-agar plates were picked up, and DNA samples extracted from the cells were analyzed at the molecular level by using the direct DNA sequencing method, as well as the Southern blot hybridization technique. For direct DNA sequencing, adenine phosphoribosyl transferase gene was chosen as a typical case of non-essential genomic gene and cytidine triphosphate synthetase as an essential one. For the Southern blot analysis, Pc-1 (Ms6-hm) was chosen as a hypervariable tandem repeat sequence, and its genomic instability was examined. We will explain the usefulness of this new experimental procedure for the evaluation of the biological effect caused by radon and its short-lived progeny.第１２回国際放射線研究会

Molecular analysis on germline mutation caused by low-dose irradiation

Genetic heterogeneity and a low frequency of germline mutation at single-copy gene loci have limited the direct measurement of germline mutation in human populations. Two confl icting results have been reported for the effect of ionizing radiation on germline mutation in human populations. A study conducted on the fi rst-generation progeny of the survivors of the atomic bombs at Hiroshima and Nagasaki found no signifi cant increase in germline mutations. On the other hand, a signifi cant increase in germline mutation was reported among the human population in the Belarus area after the Chernobyl accident in 1986. We investigated the germline mutation at the molecular level using experimental mouse strains with different genetic backgrounds to assess the risk of ionizing radiation on human populations. The C3H male parents were exposed to X ray (0, 0.3, 1, and 3Gy) and mated with unexposed C57BL females after two weeks interval, so as to detect the germline mutation occurred at the spermatid stage. Genomic DNA samples were prepared from the both parents and F1s, and the genomic DNA sequences were compared between parents and offspring at the specifi c genomic gene loci, such as adenine phosphoribosyl transferase (aprt) gene and cytidine triphosphate synthetase (ctps) gene, using the automated DNA sequencer. Also hypervariable Pc-1 (Ms6-hm) minisatellite repeat locus was analyzed by using Southern blot hybridization technique. Our preliminary results indicated that the changes of the restriction DNA fragment length in offspring did not refl ect the occurrence of the mutation, such as point mutation, insertion, and deletion, in the genomic gene loci including the intervening sequence (intron).第１２回国際放射線研究会