Crystal structure of pathogenic Staphylococcus aureus lipase complex with the anti-obesity drug orlistat

抗肥満薬が黄色ブドウ球菌の病原因子を阻害するメカニズムを解明. 京都大学プレスリリース. 2020-03-31.Staphylococcus aureus lipase (SAL), a triacylglycerol esterase, is an important virulence factor and may be a therapeutic target for infectious diseases. Herein, we determined the 3D structure of native SAL, the mutated S116A inactive form, and the inhibitor complex using the anti-obesity drug orlistat to aid in drug development. The determined crystal structures showed a typical α/β hydrolase motif with a dimeric form. Fatty acids bound near the active site in native SAL and inactive S116A mutant structures. We found that orlistat potently inhibits SAL activity, and it covalently bound to the catalytic Ser116 residue. This is the first report detailing orlistat–lipase binding. It provides structure-based information on the production of potent anti-SAL drugs and lipase inhibitors. These results also indicated that orlistat can be repositioned to treat bacterial diseases

Discovery of a new pulsating X-ray source with a 1549.1-s period, AX J183220-0840

A new pulsating X-ray source, AX J183220-0840, with a 1549.1-s period was discovered at R.A.= 18h32m20s and Dec.=-8d40'30'' (J2000, uncertainty=0.6degree) during an ASCA observation on the Galactic plane. The source was observed two times, in 1997 and in 1999. A phase-averaged X-ray flux of 1.1E-11 ergs cm-2 s-1 and pulsation period of 1549.1+/-0.4 s were consistently obtained from these two observations. The X-ray spectrum was represented by a flat absorbed power-law with a photon-index of =~0.8 and an absorption column density of =~1.3E22 cm-2. Also, a signature of iron K-shell line emission with a centroid of 6.7 keV and an equivalent width of approximately 450 eV was detected. From the pulsation period and the iron-line feature, AX J183220-0840 is likely to be a magnetic white dwarf binary with a complexly absorbed thermal spectrum with a temperature of about 10 keV.Comment: 13 pages, 4 figures, accepted for publication in ApJ Letter

Factors Predicting the Quality of Life of University Students in Japan Amidst COVID-19: A Cross-Sectional Study

Owing to the COVID-19 pandemic, classes and club activities in Japanese universities have been canceled; this may increase students’ perceived stress and adversely affect their quality of life. This study investigated the factors that influence Japanese university students’ quality of life during the pandemic. An online questionnaire collating data related to demographic characteristics, the perceived stress scale (PSS), sense of coherence (SOC), number of social supports, and quality of life (Short Form Health Survey; SF-8) was distributed to university students. Participants were divided into two groups: those who entered university before (seniors) and after (juniors) the onset of the pandemic. Their scores on the two sub-domains (physical and mental) of the SF-8 were evaluated. Multiple regression analysis was performed to identify factors associated with the composite mental summary of the SF-8. Regression analysis indicated that the predictor model of the composite mental summary differed between juniors and seniors. Among seniors, the composite mental summary was significantly indicated by the composite physical summary (b = 0.549, p < 0.0001) and PSS (b = 0.422, p < 0.0001). Among juniors, it was significantly indicated by the composite physical summary (b = 0.531, p < 0.0001), PSS (b = 0.390, p < 0.0001), and number of social supports (b = −0.148, p = 0.006). The factors associated with quality of life differed between seniors and juniors. Universities must provide opportunities for students to find more friends, especially for juniors who have limited socialization opportunities owing to the pandemic

現代アメリカ英語の諸相(2)

米国の現代小説や漫画などに見られるが、辞書などでまだ明確にされていない現代アメリカ英語の英語表現について明らかにするとともに、その背景文化について記述した

Analysis of hydroxy sphingomyelin

Sphingomyelin (SM) with N-α-hydroxy fatty acyl residues (hSM) has been shown to occur in mammalian skin and digestive epithelia. However, the metabolism and physiological relevance of this characteristic SM species have not been fully elucidated yet. Here, we show methods for mass spectrometric characterization and quantification of hSM. The hSM in mouse skin was isolated by TLC. The hydroxy hexadecanoyl residue was confirmed by electron impact ionization-induced fragmentation in gas chromatography-mass spectrometry. Mass shift analysis of acetylated hSM by time of flight mass spectrometry revealed the number of hydroxyl groups in the molecule. After correcting the difference in detection efficacy, hSM in mouse skin and intestinal mucosa were quantified by liquid chromatography-tandem mass spectrometry, and found to be 16.5 ± 2.0 and 0.8 ± 0.4 nmol/μmol phospholipid, respectively. The methods described here are applicable to biological experiments on hSM in epithelia of the body surface and digestive tract

LPA, C1P, and S1P in IPF

Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonias. Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are signaling lipids that evoke growth factor-like responses to many cells. Recent studies revealed the involvement of LPA and S1P in the pathology of IPF. In this study, we determined LPA, S1P and ceramide 1-phosphate (C1P) in peripheral blood plasma of IPF patients, and examined correlation to the vital capacity of lung (VC), an indicator of development of fibrosis. Blood plasma samples were taken from eleven patients with IPF and seven healthy volunteers. The lipids of the sample were extracted and subjected to liquid chromatography-tandem mass spectrometry for analysis. Results showed that there is a significant negative correlation between VC and plasma LPA levels, indicating that IPF patients with advanced fibrosis had higher concentration of LPA in their plasma. Average of S1P levels were significantly higher in IPF patients than those in healthy subjects. Although it is not statistically significant, a similar correlation trend that observed in LPA levels also found between VC and S1P levels. These results indicated that plasma LPA and S1P may be associated with deterioration of pulmonary function of IPF patients

LIPUS effect on osteoarthritic TMJs

The aim of this study was to assess the effect of low-intensity pulsed ultrasound (LIPUS) application on rat temporomandibular joints (TMJs) with early-stage of osteoarthritis-like conditions induced by mechanical overloading. Fifteen-week-old male Wistar rats were divided into two experimental groups and a control group (n = 10 each). Both TMJs of all rats in one experimental group were subjected to mechanical overloading for 5 d, and those in the other experimental group were exposed to LIPUS for 20 min/d after overloading. Condyles were assessed using micro-computed tomography, histology and histomorphometry. LIPUS treatment attenuated cartilage degeneration, decreased the number of osteoclastic cells and restored the expression of aggrecan after an initial decrease induced by mechanical overloading. These results indicate that LIPUS may have a protective effect on the early progression of TMJ osteoarthritis

明治初期教科書『物理階梯』のコーパス作成による語彙の考察

会議名: 言語資源活用ワークショップ2016, 開催地: 国立国語研究所, 会期: 2017年3月7日-8日, 主催: 国立国語研究所 コーパス開発センター明治5 年に文部省から刊行された『物理階梯』は，日本で初めての物理学の教科書である。発表者らは，本書のコーパス化を進めており，そのコーパスによって行った語彙調査の概要を報告し，本書の語彙の性格について若干の考察を加える。本書は，短単位で，延べ約39,000 語，異なり約4,400 語からなる。本書の語彙を，同時期の啓蒙雑誌『明六雑誌』の語彙（延べ約178,000 語，異なり約13,200 語）と比較し，本書で高頻度でありながら，『明六雑誌』で頻度0 または1 の約300語を抽出し，その性格を考察した。その結果，(1) 物理学の話題で使われる「テーマ語」，(2) 物理学の「専門語」，(3) 物理学に限定されない「学術語」に分けられた。(1) は「管」「動き」「浮かぶ」など，旧来からある語，(2) は「光線」「静止」「空気」など，蘭学以後登場した語，(2) は「距離」「両端」「中央」など従来の一般語が学術語化したものと，蘭学以後登場した新語の両方が見られた

Developing Trans-Curriculum Learning of Japanese Language Arts in a K-9 integrated school II: For nurturing students with the zest for living and with capabilities to solving their own tasks for themselves

本研究は，昨年度に引き続き，幼小中一貫校としての特色を生かして，通教科的能力を位置づけた国語科の学習開発を行うことによって，新領域「希望（のぞみ）」との関連を明らかにすることを目的としている。本年度は，幼小中各学校段階において，「物語で作者が伝えたいこと」をどのようにとらえているのかを比較・検討することによって，幼小中12年間を見通した通教科的能力の育成につなげていった。幼稚園年長児・小学校１年生・中学校３年生では「おおきなかぶ」を，小学校４年生と中学校１年生では「世界でいちばんやかましい音」を教材として，その読みを比較・検討した。結果として，読みの系統性を踏まえた課題設定を通して上位学年の読みに近づく学習活動により，通教科的能力の育成に資することができた。The purpose of this study is intended to clarify the relationship with “NOZOMI” and our developing literature units for nurturing students’ learning abilities beyond each school subject. In this paper, by examining how students make out “what authors convey through stories” in each grade levels of elementary and secondary classes, the teaching objectives for lessons for nurturing students’ abilities adapting any situations were settled. Based on the outcomes of the lessons about A BIG TURNIP(a Russian folk tale) in the eldest class in kindergarten, Grade1 and Grade9 classes, and THE LOUDEST NOISE IN THE WORLD(by Benjamin Elkin) in Grade4 and Grade7 classes, any features of students’ responses were revealed through comparing and examining reader responses to each texts in each grades. For developing “NOZOMI” related learnings, it would be important to implement learning activities with the task settings following the ladders for reading development so much

Novel SPEF2 Variant in a Japanese Patient with Primary Ciliary Dyskinesia: A Case Report and Literature Review

Primary ciliary dyskinesia (PCD) is a genetic and congenital disease associated with an abnormal ciliary ultrastructure and function and is estimated to affect 1 in 15,000–20,000 individuals. A PCD diagnosis can be achieved by genotyping. Here, we performed whole-exome analysis for the diagnosis of PCD and described the detailed clinical characteristics of the case. A 39-year-old Japanese woman with sinusitis and bronchiectasis without situs inversus had had upper and lower respiratory symptoms since childhood and had received long-term macrolide therapy without an accurate diagnosis. A moderate deterioration of cilia function was observed by high-speed video microscopy analysis; additionally, the number of cells with moving cilia was fewer than that in patients without PCD. Electron microscopy revealed no apparent structural abnormalities. We performedwhole-exome analysis and identified novel biallelic variants of SPEF2 in the homozygous state (c.1860_1861insCT).We confirmed the absence of SPEF2 protein expression in the cilia of the nasal mucosa using fluorescent immunostaining. Accordingly, she was diagnosed as having PCD with the SPEF2 variant. The present case suggests that the deterioration of cilia function is moderate, the number of respiratory cells with moving cilia might be reduced, and the respiratory condition could be severe in patients with PCD with the SPEF2 variant