31 research outputs found

    ミャンマー産植物Premna serratifoliaとJatropha multifida及び海綿Clathria proliferaに含まれるメラニン産生制御成分に関する研究

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    富山大学・富医薬博甲第305号・禹 昭年・2019/03/26当該博士論文は以下の項評論文で構成されています。①Woo, SY., Win, N.N., Wong, C.P. et al. Two new pyrrolo-2-aminoimidazoles from a Myanmarese marine sponge, Clathria prolifera, J Nat Med (2018) 72: 803-807. https://doi.org/10.1007/s11418-018-1205-y This is a pre-print of an article published in Journal of Natural Medicines. The final authenticated version is available online at: https://doi.org/10.1007/s11418-018-1205-y”.②So-Yeun Woo et al. Lignans with melanogenesis effects from Premna serratifolia wood, Fitoterapia (2019) 133:35-42. https://doi.org/10.1016/j.fitote.2018.12.008③So-Yeun Woo et al. A New Tetrahydrofuran Lignan from Premna serratifolia Wood, Natural Product Communications (2019) 14:113-116. https://doi.org/10.1177/1934578X1901400130富山大

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

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    「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

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    「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

    Chojalactones A–C, Cytotoxic Butanolides Isolated from <i>Streptomyces</i> sp. Cultivated with Mycolic Acid Containing Bacterium

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    The soil-derived bacterium, <i>Streptomyces</i> sp. CJ-5, was cocultured with the mycolic acid-containing bacterium <i>Tsukamurella pulmonis</i> TP-B0596. The combined culture method significantly enhanced the production of the secondary metabolites in <i>Streptomyces</i> sp. CJ-5, leading to the isolation of three novel butanolide chojalactones A–C (<b>1</b>–<b>3</b>), with unusual γ-butyrolactone scaffolds. The complete structures, including the absolute configurations of <b>1</b>–<b>3</b>, were determined based on spectroscopic data and total syntheses. In methylthiazole tetrazolium (MTT) assays, <b>1</b> and <b>2</b> showed moderate cytotoxicity against P388 cells

    Transcranial Extracellular Impedance Control (tEIC) Modulates Behavioral Performances

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    <div><p>Electric brain stimulations such as transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), and transcranial alternating current stimulation (tACS) electrophysiologically modulate brain activity and as a result sometimes modulate behavioral performances. These stimulations can be viewed from an engineering standpoint as involving an artificial electric source (DC, noise, or AC) attached to an impedance branch of a distributed parameter circuit. The distributed parameter circuit is an approximation of the brain and includes electric sources (neurons) and impedances (volume conductors). Such a brain model is linear, as is often the case with the electroencephalogram (EEG) forward model. Thus, the above-mentioned current stimulations change the current distribution in the brain depending on the locations of the electric sources in the brain. Now, if the attached artificial electric source were to be replaced with a resistor, or even a negative resistor, the resistor would also change the current distribution in the brain. In light of the superposition theorem, which holds for any linear electric circuit, attaching an electric source is different from attaching a resistor; the resistor affects each active electric source in the brain so as to increase (or decrease in some cases of a negative resistor) the current flowing out from each source. From an electrophysiological standpoint, the attached resistor can only control the extracellular impedance and never causes forced stimulation; we call this technique transcranial extracellular impedance control (tEIC). We conducted a behavioral experiment to evaluate tEIC and found evidence that it had real-time enhancement and depression effects on EEGs and a real-time facilitation effect on reaction times. Thus, tEIC could be another technique to modulate behavioral performance.</p></div

    Behavioral experiment.

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    <p>A selective response (mouse-click) task for visually presented stimuli was performed. (a) Top: Visual stimulus sequence. Each stimulus is presented for a duration of 1/15 s with a stimulus onset asynchrony (SOA) of 0.8–1.2 s at a random location along the four-degree visual angle circle (the circle was invisible). Bottom: Images L and R for the selective mouse-click. (b) A total of 512 trials (128 trials×4 runs) were divided into 32 blocks (16 trials for each block). The tEIC conditions, Sham, Type I, Type II, and Noise, were randomly switched every block (the Noise condition was excluded from further analyses due to electronics problems). Note that tEIC was simultaneously (not in a before-and-after manner) applied to the behavioral experiment.</p
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