Role of Ca2+ in the rapid cooling-induced Ca2+ release from sarcoplasmic reticulum in ferret cardiac muscles

Rapid lowering of the solution temperature (rapid cooling, RC) from 24 to 3°C within 3 s releases considerable amounts of Ca2+ from the sarcoplasmic reticulum (SR) in mammalian cardiac muscles. In this study, we investigated the intracellular mechanism of RC-induced Ca2+ release, especially the role of Ca2+, in ferret ventricular muscle. Saponin-treated skinned trabeculae were placed in a glass capillary, and the amount of Ca2+ released from the SR by RC and caffeine (50 mM) was measured with fluo-3. It was estimated that in the presence of ATP about 45% of the Ca2+ content in the SR was released by RC. The amount of SR Ca2+ released by RC was unchanged by the replacement of ATP by AMP-PCP (a non-hydrolysable ATP analogue and agonist for the ryanodine receptor but not for the Ca2+ pump of SR), suggesting that the suppression of the Ca2+ pump of SR at low temperature might not be a major mechanism in RC-induced Ca2+ release. The free Ca2+ concentration of the solution used for triggering RC-induced Ca2+ release was estimated to be only about 20 nM with fluo-3 or aequorin. When this solution was applied to the preparation at 3°C, only a small amount of Ca2+ was released from SR presumably by the Ca2+-induced Ca2+ release (CICR) mechanism. Thus, in mammalian cardiac muscles, RC releases a part of the (<50%) stored Ca2+ contained in the SR, and the mechanism of RC-induced Ca2+ release may differ from that of CICR, which is thought to play a role in frog skeletal muscle fibres that express ryanodine receptors of different types

バランス型紙を用いた集団食事指導 ―企業健康保険組合主催のセミナーの場合―

Corporate health insurance societies in Hyogo organized a pilot seminar according to“ Health check up specifically programmed against metabolic syndrome followed by specific health counseling” which is known as a national project since 2008. At the seminar, we developed a diet balance sheet（ DBS） for management and prevention of obesity. 356 women were registered to our weight management program, were instructed how to use the DBS. After the completion of each seminar, we asked their body weight and abdominal circumference at the transitional period. 125 women responded to our questions. 89 women（ 71.2% of the respondents） improved their physical condition after the seminar by the use of DBS. In addition, 42 women of the respondents reduced their body weight. Our DBS was confirmed to be effective as the diet education material for the seminar clients. It is expected to be applicable widely for management and prevention of lifestyle-related diseases. We need to establish much more effective program and to make a support system for the specific health counseling

ネンチョウジ ノ スキー ノ トリクミ ニツイテ : ホッカイドウ ブンキョウ ダイガク フゾク ヨウチエン ネンチョウグミ ノ スキー ジュギョウ

雪国に育つ子どもたちが、幼児期からスキーに親しむことが必要と、附属幼稚園においてスキー学習を行っている。平成22 年度は1 月〜3 月まで8 回、年長児5 歳児スキー授業を行った。経験のある幼児が少ない状態で始まったが、最終的に、すべての子がリフトで山の上まで登り、自力で滑り降りることができた。　スキーの技術習得にとどまらず自信をつけた、自尊感情を高めた等の保育上の成果を得たが、この反省を踏まえ、さらに、保護者の期待をアンケートで把握し、子どもたちひとりひとりの保育課題を明らかにした、スキー学習の取り組み案を編成した

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

Utero-ovarian varices and absent inferior vena cava in pregnancy.

Extensively distended and tortuous vessels on both sides of the uterus are rare incidental findings on transvaginal sonography in early pregnancy. A 31-year-old woman with a history of surgical repair for congenital intestinal stenosis was noted to have utero-ovarian varices on a transvaginal ultrasound examination during her first prenatal visit at 6 weeks' gestation. Magnetic resonance imaging revealed dilated ovarian veins along with infrarenal absence of inferior vena cava as well as the absence of external and common iliac veins. Despite concerns regarding spontaneous utero-ovarian vessels rupture, her antenatal course was uneventful. A vaginal delivery was successfully achieved without any postpartum complication. We also demonstrated an intraoperative view of the utero-ovarian vessels during cesarean section in her subsequent pregnancy. Absence of inferior vena cava and pelvic varices can occur in women with a history of neonatal surgery. Although the risk of utero-ovarian varices rupture remains unclear, vaginal delivery may be safely achieved