２００８年の気温からみた佐世保市の環境について

２１世紀に入り、地球温暖化が益々大きな社会問題となっている。本論文では、気象庁が発表した最高気温、最低気温及び平均気温のデータをもとに、２００８年の佐世保市における月別及び年間の最高気温、最低気温及び平均気温の平均値、冬日、真冬日、夏日、真夏日、猛暑日、熱帯夜の出現回数を調査し、２００１年から２００７年のそれらの平均値と比較した。その結果、２００８年の月別及び年間の最高気温、最低気温及び平均気温は、２００１年から２００７年と比較して極端に暑かったり寒かったりすることはなかった。２００８年の日々の気温においては、冬日が２月に２回、真冬日は０回、夏日は４月から１０月まで１４５回、真夏日は６５回、猛暑日は３回、熱帯夜は４３回観測された。なお、７月と８月は全日夏日であり、９月もほぼ夏日であった。また、７月６日から８月１８日まで４４日間連続して真夏日若しくは猛暑日であった。２００１年から２００７年と比較すると、夏日、真夏日、猛暑日の出現回数に大きな変化はみられなかったが、熱帯夜の出現回数の増加及び冬日の出現回数の減少がみられ、２００１年以降という短期間においても地球温暖化の影響がみられるものとなっている。Global warming is one of the major environmental problems of the 21 st Century. In this paper, we investigate the frequencies of cold and very cold days in winter, hot, tropical and very hot days in summer, and tropical nights in Sasebo using data on maximum, minimum, and average temperatures published by the Japan Meteorological Agency. Based on monthly average temperatures in 2008, the climate in Sasebo remained unchanged when compared with those values from 2001 to 2007. The frequencies of frosty, icy, hot, tropical, and very hot days and tropical nights in 2008 were 2 times, 0times, 145times, 65times, 3times and 43times, respectively. While the frequencies of summer, tropical, and very hot days were similar to those frequencies from 2001 to 2007, an increase in the number of tropical nights and a decrease in the number of frosty days were confirmed. As a result, the influence of global warming since 2001 is believed to have been observed

Stability Testing of Drug Products Approved by the Japanese Government in 2014

2014年に日本で承認された新医療用製剤に対し､安定性試験の現状を調査した｡我々は､2014年に安定性試験の記述がある134の新医療用製剤を特定した｡長期保存試験としては､82製剤が25±2℃/60±5%相対湿度の条件下で､48製剤が5±3℃の条件下で､4製剤が10℃未満の条件下で試験が実施されていた｡また､光安定性試験では､78製剤が光学的に安定であったが､48製剤は光学的に不安定であった.光学的に不安定な製剤は､遮光保存をするといった適切な保存方法がとられている.これらの結果から､2014年に日本で承認された新医療用製剤は､ICH ｶﾞｲﾄﾞﾗｲﾝに従って､適正に承認されていることがわかった｡We investigated the current status of stability testing of new drug products in Japan. One hundred thirty-four new drug products that had undergone stability testing in 2014 were identified. Among these, 82 were tested at 25℃ ± 2℃ / 60% ± 5% relative humidity, 48 were tested at 5℃ ± 3℃, and 4 were tested at less than 10℃ on long-term testing. Based on photostability testing, 78 new drug products were found to be optically stable and 48 were optically unstable. New drug products that appeared unstable in photostability testing were stored in the dark. Based on these results, the new drug products approved in Japan according to the ICH guidelines in 2014 were found to have been adequately tested

Stability Testing of Drug Products Approved by the Japanese Government in 2015

2015年に日本で承認された新医療用製剤に対し、安定性試験の現状を調査した。我々は、2015年に安定性試験の記述がある81の新医療用製剤を特定した。長期保存試験としては、5製剤が30±2℃/65±5％相対湿度の条件下で、55製剤が25±2℃/60±5％相対湿度の条件下で、21製剤が5±3℃の条件下で試験が実施されていた。また、加速性試験では、60製剤が40±2℃/75±5％相対湿度の条件下で実施されていた。17製剤は25±2℃/60±5％相対湿度の条件下で実施された。3製剤は温度及び試験期間がマスキングされていて、不明であった。1製剤は半減期が短いため、加速試験は実施されなかった｡これらの結果から、2015年に日本で承認された新医療用製剤は、1つを除いて ICH ガイドラインに従って、適正に承認されていることがわかった

ERRγ agonist under mechanical stretching manifests hypertrophic cardiomyopathy phenotypes of engineered cardiac tissue through maturation

iPS細胞から成熟した人工心筋組織の作製方法の開発 肥大型心筋症の治療法開発への利用に期待. 京都大学プレスリリース. 2023-10-06.Stretching and stimulating engineered heart tissues to accurately portray hypertrophic cardiomyopathy. 京都大学プレスリリース. 2023-10-17.Engineered cardiac tissue (ECT) using human induced pluripotent stem cell-derived cardiomyocytes is a promising tool for modeling heart disease. However, tissue immaturity makes robust disease modeling difficult. Here, we established a method for modeling hypertrophic cardiomyopathy (HCM) malignant (MYH7 R719Q) and nonmalignant (MYBPC3 G115∗) pathogenic sarcomere gene mutations by accelerating ECT maturation using an ERRγ agonist, T112, and mechanical stretching. ECTs treated with T112 under 10% elongation stimulation exhibited more organized and mature characteristics. Whereas matured ECTs with the MYH7 R719Q mutation showed broad HCM phenotypes, including hypertrophy, hypercontraction, diastolic dysfunction, myofibril misalignment, fibrotic change, and glycolytic activation, matured MYBPC3 G115∗ ECTs displayed limited phenotypes, which were primarily observed only under our new maturation protocol (i.e., hypertrophy). Altogether, ERRγ activation combined with mechanical stimulation enhanced ECT maturation, leading to a more accurate manifestation of HCM phenotypes, including non-cardiomyocyte activation, consistent with clinical observations

Comparative Study of Chemical Oxygen Demand and Total Organic Carbon in Omura Bay

化学的酸素要求量(COD)と全有機炭素量(TOC)を測定することにより､大村湾における有機汚濁ﾚﾍﾞﾙを評価した｡本研究では､2008年5月から2010年5月にかけ､水深別(0､2､6､10m)に5地点(湾口部､湾央部､湾奥部3地点)より採水し､両者を測定した｡その結果､COD は 0.68～3.94mg/L(平均 1.95mg/L)､TOC は 0.811～2.170mg/L(平均 1.345mg/L)となり､COD では試料の約半数が環境基準の 2mg/L 以上を示したのに対し､TOC ではほぼ全試料で 2mg/L 以下となり､COD と比べて低値を示した｡両者とも表層で高く､深度とともに低い傾向を示した｡Pearson の積率相関分析を行った結果､両者の間には正の相関がみられた(相関係数:0.604)｡また､海水交換が十分でないと示唆される湾奥部ほど､両者の相関性が高くなる傾向がみられた｡以上の結果より､閉鎖性海域ほど両者の相関性が高く､TOC の測定は水質汚濁を把握するには有効であることが示唆された｡The organic pollutant levels in Omura Bay were evaluated by measuring chemical oxygen demand(COD)and total organic carbon(TOC). We investigated these factors in Omura Bay from May 2008 to May 2010, in order to clarify the relationship between them. Samples were collected from four depths(0, 2, 6, and 10 m)at five sites. The COD values ranged from 0.68 to 3.94 mg/L with a mean value of 1.95 mg/L, while the TOC values ranged from 0.811 to 2.170 mg/L with a mean value of 1.345 mg/L. Although half of the samples showed high COD values(>2.0 mg/L), most of the samples showed low TOC values(<2.0 mg/L). The samples from the upper layer showed higher COD and TOC values than the samples from the middle or bottom layers. A significant positive correlation between the COD and TOC values was obtained(0.604); furthermore, a strong correlation between these parameters was observed for the samples obtained from the inner bay. These results suggest that measuring TOC may be useful for estimating the degree of pollution in enclosed coastal sea areas

ERRγ enhances cardiac maturation with T-tubule formation in human iPSC-derived cardiomyocytes

ヒトのiPS細胞から新生児レベルまで成熟した心筋細胞を作製する. 京都大学プレスリリース. 2021-06-21.Lowering the cost of heart cell therapies. 京都大学プレスリリース. 2021-06-21.One of the earliest maturation steps in cardiomyocytes (CMs) is the sarcomere protein isoform switch between TNNI1 and TNNI3 (fetal and neonatal/adult troponin I). Here, we generate human induced pluripotent stem cells (hiPSCs) carrying a TNNI1[EmGFP] and TNNI3[mCherry] double reporter to monitor and isolate mature sub-populations during cardiac differentiation. Extensive drug screening identifies two compounds, an estrogen-related receptor gamma (ERRγ) agonist and an S-phase kinase-associated protein 2 inhibitor, that enhances cardiac maturation and a significant change to TNNI3 expression. Expression, morphological, functional, and molecular analyses indicate that hiPSC-CMs treated with the ERRγ agonist show a larger cell size, longer sarcomere length, the presence of transverse tubules, and enhanced metabolic function and contractile and electrical properties. Here, we show that ERRγ-treated hiPSC-CMs have a mature cellular property consistent with neonatal CMs and are useful for disease modeling and regenerative medicine

大村湾における貧酸素分布について

一般に閉鎖性水域においては貧酸素水塊(溶存酸素:DO 3.0mg/L 以下)が発生しやすいことが知られており､魚介類の生育･生息に障害を及ぼすことが指摘されている｡本研究では､典型的な閉鎖性水域である大村湾における貧酸素水塊の発生状況を調査するために､平成20年(2008年)2月から平成21年(2009年)2月にかけて､水深別(0､2､6､10m)に5地点(湾口部､湾央湾､湾奥部3地点)より採水し､DO を含む各種水質項目を測定した｡その結果､9月における湾奥部の水深6m 以下において DO が 3.0mg/L 以下であり､貧酸素水塊の発生が認められた｡湾奥部においては5月における表層と底層(水深 10m)との温度差が湾央部や湾口部と比較して大きく､5月以降水温成層が形成し始めていることが示唆された｡なお､湾央部や湾口部においても水深 10m で DO が 3.5mg/L 以下と貧酸素水塊に準ずる状態の発生が認められた｡しかし､11月にはいずれの地点においても水深 10m で DO が 5.0mg/L 以上と貧酸素水塊が消失していることがわかった｡Generally, it is known that the hypoxic water mass(Dissolved Oxygen: DO<3.0mg/L)is easy to be formed in an enclosed coastal sea. As Omura Bay is a typical enclosed coastal sea, the oxygen content of seawater was measured in Omura Bay from February in 2008 to February in 2009. Samples were collected from four depths(0, 2, 6, and 10m)at five sites. The hypoxic water mass were observed at bottom water in September, especially at inner bay, which water column was began to develop in May

改質乳清ﾀﾝﾊﾟｸ質の加熱臭の抑制とｹﾞﾙ形成能に及ぼす食塩添加の影響

改質乳清ﾀﾝﾊﾟｸ質(Process Whey Protein:PWP)のｹﾞﾙ特性を調理･加工へ利用する基礎資料を得るため､ｶﾞｽｸﾛﾏﾄｸﾞﾗﾌｨｰにより PWP のﾍｯﾄﾞｽﾍﾟｰｽｶﾞｽ中における揮発性成分の捕集および同定を行い､PWP の加熱臭について検討した｡また､PWP は塩を加え加熱することでｹﾞﾙ化することから､塩は一般に調理で使用する食塩について､PWP のｹﾞﾙ形成能に及ぼす食塩添加量および PWP の使用量の影響を調べた｡(1) ｶﾞｽｸﾛﾏﾄｸﾞﾗﾌｨｰ分析では､加熱前の PWP ではみられなかった新たなﾋﾟｰｸが加熱後の PWP では出現し､その新たな出現ﾋﾟｰｸは保持時間が6.89分であることから､ﾍﾌﾟﾀﾅｰﾙと同定した｡また､ﾀﾏﾈｷﾞﾊﾟｳﾀﾞｰ添加群および茶抽出物製剤添加群ともに濃度依存的にﾋﾟｰｸ面積が減少し､牛乳特有のにおいが減少した｡(2) 食塩添加量および PWP の使用量が増すとともに濃度依存的に硬く､付着性に富んだｹﾞﾙを形成した｡To obtain the basic materials for utilizing the gel property of process whey protein(PWP)in cooking and processing, we examined the smell of PWP by collecting and identifying the volatile components in the gas of PWP in a head-space, using a gas chromatography. As PWP could be gelled by adding salt and heating, we examined the effect of the added amount of table salt upon the gel formation ability of PWP and the amount of PWP used, in regard to the table salt that is generally used in cooking.(1) In the analysis of gas chromatography, a new peak that was not observed in PWP before heating appeared after heating, and, as the retention time of the new peak was 6.89 minutes, we identified it as heptanal. Also, in both the onion-powder added group and the tea-extract preparation added group, the peak area decreased concentration-dependently, and the smell peculiar to a cow\u27s milk decreased.(2) With the increasing amount of table-salt added and of the PWP used, a gel, which became hardened concentration-dependently and became full of adhesion, was formed

Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice

金沢大学医薬保健研究域医学系Oxytocin sets the stage for childbirth by initiating uterine contractions, lactation and maternal bonding behaviours. Mice lacking secreted oxcytocin (Oxt -/-, Cd38 -/-) or its receptor (Oxtr -/-) fail to nurture. Normal maternal behaviour is restored by peripheral oxcytocin replacement in Oxt -/- and Cd38 -/-, but not Oxtr -/- mice, implying that circulating oxcytocin crosses the blood-brain barrier. Exogenous oxcytocin also has behavioural effects in humans. However, circulating polypeptides are typically excluded from the brain. We show that oxcytocin is transported into the brain by receptor for advanced glycation end-products (RAGE) on brain capillary endothelial cells. The increases in oxcytocin in the brain which follow exogenous administration are lost in Ager -/- male mice lacking RAGE, and behaviours characteristic to abnormalities in oxcytocin signalling are recapitulated in Ager -/- mice, including deficits in maternal bonding and hyperactivity. Our findings show that RAGE-mediated transport is critical to the behavioural actions of oxcytocin associated with parenting and social bonding.3082047