FACTOR ANALYSIS OF SPRINT PHASES ON THE SPEED CURVE OF THE 100M DASH

Previous studies have indicated that the speed curve of the 100m dash consists of some distinct phases which can be used to analyze an athlete's performance. The purpose of this study was to introduce a method using a portable computer as a device for the measurement of sprint time and the illustration of the speed curve, and to clarify a simple model of sprint phases on the factor structure. Based on the data of 133 participants, principal factor solution was given to the correlation matrix, and varimax rotation was applied to simplify the factorial structure of sprint phases. Finally, two factors were extracted and interpreted. It is suggested that this method is useful for measurement and evaluation in the 100m dash, and that a simple model of sprint phases may be explained by these two factors. These findings are important in predicting the ability of 100m sprinters and in considering coaching methods in terms of technique, training, strategy, etc

Differential Response of Heat-Shock-Induced p38 MAPK and JNK Activity in PC12 Mutant and PC12 Parental Cells for Differentiation and Apoptosis

Among the 3 mitogen-activated protein kinases -- ERK, p38 MAPK and JNK -- JNK has been suggested to participate in apoptosis, whereas p38 MAPK is thought to be part of the differentiation response. There are many common inducers of JNK and p38 MAPK, but the mechanisms underlying the differential response to apoptosis and differentiation are poorly understood. We found that heatshock activated p38 MAPK at 3min after exposure to a temperature of 44 in stress-hypersensitive PC12m3 mutant cells, while it activated JNK at 20min after the same heat treatment. However, heat shock activated p38 MAPK 5min after heat treatment and JNK 10min after heat treatment in PC12 parental cells. The extent of phosphorylation of p38 MAPK induced by heat shock in PC12m3 cells was significantly greater than that in PC12 parental cells, and a high level of heat-shock-induced neurite outgrowth was observed only in PC12m3 cells. On the other hand, heat-shock-induced JNK activation appeared more quickly and apoptosis started earlier in PC12 parental cells. These findings indicate that short stress induces p38 MAPK and longer stress induces JNK, and that the response of these kinases to heat shock differs depending on cell type.</p

E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis

Chronic hepatic damage leads to liver fibrosis, which is characterized by the accumulation of collagen-rich extracellular matrix. However, the mechanism by which E3 ubiquitin ligase is involved in collagen synthesis in liver fibrosis is incompletely understood. This study aimed to explore the involvement of the E3 ubiquitin ligase synoviolin (Syno) in liver fibrosis.The expression and localization of synoviolin in the liver were analyzed in CCl(4)-induced hepatic injury models and human cirrhosis tissues. The degree of liver fibrosis and the number of activated hepatic stellate cells (HSCs) was compared between wild type (wt) and Syno(+/-) mice in the chronic hepatic injury model. We compared the ratio of apoptosis in activated HSCs between wt and Syno(+/-) mice. We also analyzed the effect of synoviolin on collagen synthesis in the cell line from HSCs (LX-2) using siRNA-synoviolin and a mutant synoviolin in which E3 ligase activity was abolished. Furthermore, we compared collagen synthesis between wt and Syno(-/-) mice embryonic fibroblasts (MEF) using quantitative RT-PCR, western blotting, and collagen assay; then, we immunohistochemically analyzed the localization of collagen in Syno(-/-) MEF cells.In the hepatic injury model as well as in cirrhosis, synoviolin was upregulated in the activated HSCs, while Syno(+/-) mice developed significantly less liver fibrosis than in wt mice. The number of activated HSCs was decreased in Syno(+/-) mice, and some of these cells showed apoptosis. Furthermore, collagen expression in LX-2 cells was upregulated by synoviolin overexpression, while synoviolin knockdown led to reduced collagen expression. Moreover, in Syno(-/-) MEF cells, the amounts of intracellular and secreted mature collagen were significantly decreased, and procollagen was abnormally accumulated in the endoplasmic reticulum.Our findings demonstrate the importance of the E3 ubiquitin ligase synoviolin in liver fibrosis

Stelleralides A–C, Novel Potent Anti-HIV Daphnane-Type Diterpenoids from Stellera chamaejasm e L.

Three novel 1-alkyldaphnane-type diterpenes, stelleralides A-C (4-6), and five known compounds were isolated from the roots of Stellera chamaejasme L. The structures of 4-6 were elucidated by extensive spectroscopic analyses. Several isolated compounds showed potent anti-HIV activity. Compound 4 showed extremely potent anti-HIV activity (EC(90) 0.40 nM) with the lowest cytotoxicity (IC(50) 4.3 μM) and appears to be a promising compound for development into anti-AIDS clinical trial candidates

Isolation, Structure Determination, and Anti-HIV Evaluation of Tigliane-Type Diterpenes and Biflavonoid from Stellera chamaejasme

Five novel tigliane-type diterpenes, stelleracins A–E (3–7), a novel flavanone dimer, chamaeflavone A (8), and six known compounds were isolated from roots of Stellera chamaejasme. Their structures were elucidated by extensive spectroscopic analyses. The isolated compounds were evaluated for anti-HIV activity in MT4 cells. New compounds 3–5 showed potent anti-HIV activity (EC90 0.00056–0.0068 μM) and relatively low or no cytotoxicity (IC50 4.4–17.2 μM). These new compounds represent promising new leads for development into anti-AIDS clinical trial candidates

Beam and SKS spectrometers at the K1.8 beam line

High-resolution spectrometers for both incident beams and scattered particles have been constructed at the K1.8 beam line of the Hadron Experimental Facility at J-PARC. A point-to-point optics is realized between the entrance and exit of QQDQQ magnets for the beam spectrometer. Fine-pitch wire chamber trackers and hodoscope counters are installed in the beam spectrometer to accept a high rate beam up to 107 Hz. The superconducting kaon spectrometer for scattered particles was transferred from KEK with modifications to the cryogenic system and detectors. A missing-mass resolution of 1.9 ± 0.1 MeV/c2 (FWHM) was achieved for the ∑ peaks of (π±, K+) reactions on a proton target in the first physics run of E19 in 2010

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

細胞の三次元様増殖を指標とした温熱療法の最適条件に関する研究

本研究の目的は、三次元様増殖に温熱刺激が効果的に働く最適量と最小量を示すことであった。C3H10T1/2マウス線維芽細胞とハイドロキシアパタイトを混合し、設定温度が40℃・41.5℃・43℃・44℃・45℃、処理時間は2分間・10分間・15分間・20分間・30分間・45分間・60分間・90分間・180分間・360分間の温熱刺激を与えて10週間培養することにより三次元様増殖形成に必要な最小と最適な温熱量を調べた。その結果、三次元様増殖形成に必要な最小の温熱量は43℃2分間、また最適な温熱量は43℃10分間であった。43℃2分間は非処理対照の1.7倍、43℃10分間では3.7倍と非常に高い形成率となり、それぞれ有意差がみられた(p<0.05)。また、40℃で90分間・180分間と41.5℃15分間および44℃10分間も対照群に比べ高い形成率であった。43℃10分間の温熱処理では1週間後に約80%がアポトーシスになっていた。ウエスタンブロット分析により43℃10分間の温熱処理によってp38 MAPK の活性化が明らかであった。これらの結果から、温熱刺激による三次元様増殖はp38 MAPK の経路を介していることが判明した。本研究結果は最適な温熱量を提示するものとして温熱療法の基礎となり、温熱療法の効果を細胞生物学的に示すための重要な知見になると考えられる

神経成長因子非誘導PC12変異細胞に対する超低周波振動音刺激による神経突起の誘導

NGF 存在下のPC12変異細胞に対し、2Hz から10Hz までの超低周波振動音刺激を、30分間、50dB の条件の下与えた結果、5～10Hz の超低周波振動音刺激は、神経突起の成長を大きく促した。そして、NGF 添加のみのコントロール群に対する、神経突起成長率は8Hz の刺激が最も高く、コントロール比で約4倍の神経突起成長を促した。p38MAP キナーゼの活性化は、PC 変異細胞のニューロンの分化において重要な役割を果たす。そこで、PC12変異細胞において神経突起成長を促す超低周波振動音刺激が、p38MAP キナーゼの活性効果によって生じるかどうかの実験を行った。その結果、2～10Hz の超低周波振動音刺激が、p38MAP キナーゼの活性化を高める効果が証明された。この結果は、超低周波振動音刺激の効果は、PC12変異細胞内で神経突起成長を促すp38MAP キナーゼ・シグナル伝達経路があることを示唆している