Photo-induced imine reduction by a photoredox biocatalyst consisting of a pentapeptide and a Ru bipyridine terpyridine complex

Kano R., Oohora K., Hayashi T. Photo-induced imine reduction by a photoredox biocatalyst consisting of a pentapeptide and a Ru bipyridine terpyridine complex. Journal of Inorganic Biochemistry 259, 112657 (2024); https://doi.org/10.1016/j.jinorgbio.2024.112657.Imine reduction is a useful reaction in the preparation of amine derivatives. Various catalysts have been reported to promote this reaction and photoredox catalysts are promising candidates for sustainable amine synthesis. Improvement of this reaction using biomolecule-based reaction scaffolds is expected to increase the utility of the reaction. In this context, we have recently investigated photoredox Ru complexes with pentapeptide scaffolds via coordination bonds as catalysts for photoreduction of dihydroisoquinoline derivatives. First, Ru bipyridine terpyridine complexes coordinated with five different pentapeptides (XVHVV: X = V, F, W, Y, C) were prepared and characterized by mass spectrometry. Catalytic activities of the Ru complexes with XVHVV were evaluated for photoreduction of dihydroisoquinoline derivatives in the presence of ascorbate and thiol compounds as sacrificial reagents and hydrogen sources. Interestingly, the turnover number of the Ru complex with VVHVV is 531, which is two-fold higher than that of a simple Ru complex with an imidazole ligand. The detailed emission lifetime measurements indicate that the enhanced catalytic activity provided by the peptide scaffold is caused by an efficient reaction with the thiol derivative to accelerate reductive quenching of Ru complex. The quenching behavior suggests formation of an active species such as a Ru(I) complex. These findings reveal that the simple pentapeptide serves as an effective scaffold to enhance the photocatalytic activity of a photoactive Ru complex

Chemical properties of surface waters in the limestone regions of western Japan: Evaluation of chemical conditions for the deposition of tufas

In order to understand the chemical conditions for the depositionof tufas, chemical properties of were investigated for the 201 surface waters collected from the limestone regions including newly discovered localities of tufas. The collected waters were categorized, according to the association with tufas, mainly into; category N (waters without tufa deposition), category T (waters depositing tufas), and category S (spring waters of tufa-depositing streams). These three categories clearly differ in Ca contents, equilibrium CO 2 partial pressure (PCO2), and saturation index for calcite (SIC); all of which are the most important chemical properties for the deposition of tufas. The waters of the category N are characterized by small Ca contents (mainly 15～35 ppm) and low PCO2(350～1,000 µatm) which indicate that they are basically flowing on a limestone substrate without an efficient CO2 uptake from soils. Their SIC never exceeds +0.5. The waters depositing tufas (category T) normally exhibitCa contents more than 45 ppm and PCO2 ranging 500～2,000 µatm. The waters of category S show comparable or slightly larger Ca contents than category T, however their PCO2 is considerably higher (than 2,000 µatm). Their raised values of Ca contents and PCO2 are ascribed to efficient CO2 uptake in a soil layer and subsequent dissolution of CaCO3. Furthermore, their SIC around 0.0 indicates that the waters dissolve CaCO3 until they reach the saturation in underground water systems. The large difference in PCO2 between categories T and S results from degassing of CO2 during flowing on the streams. The degassing increases pH and SIC of the waters. The SIC of category T mostly exceeds +0.5, that is probably the most important chemical condition for an efficient deposition of tufas. This study indicates that tufas are not very rare, but also that their distribution tends to be concentrated in a certain area, such as northwestern Okayama Prefecture. Local geological and hydrological conditions can be also important controls for deposition of tufas

継続教育を見通した短大教職課程の教育

Our college has teachers training course of physical and health education. Our many students want to get teacher\u27s license when they get into the college. They study hard special subjects on pedagogy, educational psychology, teaching methods, and gymnastics, swimming, dancing, basketball etc. And they have to have special lectures by the headmasters of junior high schools. When they become the second-year students, they have teaching practice at junior high schools as student teachers for 2 or 3 weeks. They say they have had hard, fruitful and exciting days. And they hope to be teachers or sports instructors. Some of them want to go to university to study furthermore. Teachers training program in junior college has contributed when they think and choose their vocation

スポーツ社会学におけるスキー場開発研究の位置づけに関する一視角 : 観光地理学を参考にして

The aim of this study was to create an original method in sport sociology concerned with the ski area development in Japan. At first, the general research tendencies for tourist geography (tourism) were reviewd in this country. In 1960\u27s, Y. Koike described the purpose, the method and the objects of tourist geography. He pointed out that the purpose of tourism was to clarify the region itself as the total body by explaining of its personality and its spatial arrangement. In 1970\u27s, influenced by the structual-functional theory, J. Yamamura described the central viewpoint of the geographical researches. He said that the point of view was drawn by grasping the substance of the tourist regions. In 1980\u27s, H. Ishii insisted on the significance of historical perspective for the tourism studies. Second, the several studies on ski area were reviewed. They were described on the point of geographical concern and each had the special issue of the features related to the region. Third, the researches on the development of ski area and lodging facilities (minshuku) were reviewd for the next step. H. Ishii compared the minshuku in ski area with it in the seaside recreational zone. S. Shirasaka reported the characteristics of the change about the several major ski areas in Japan. In the geographical researches, it was sought to describe the region as a total bady. Of course they included social issues, but more social viewpoint must be required for the sociological study. Especially, it is nessecery to resarch from the standpoint of dwellers in ski area, because the developments influence directly on them

Assessing white matter microstructural changes in idiopathic normal pressure hydrocephalus using voxel-based R2* relaxometry analysis

BackgroundR2* relaxometry and quantitative susceptibility mapping can be combined to distinguish between microstructural changes and iron deposition in white matter. Here, we aimed to explore microstructural changes in the white matter associated with clinical presentations such as cognitive impairment in patients with idiopathic normal-pressure hydrocephalus (iNPH) using R2* relaxometry analysis in combination with quantitative susceptibility mapping.MethodsWe evaluated 16 patients clinically diagnosed with possible or probable iNPH and 18 matched healthy controls (HC) who were chosen based on similarity in age and sex. R2* and quantitative susceptibility mapping were compared using voxel-wise and atlas-based one-way analysis of covariance (ANCOVA). Finally, partial correlation analyses were performed to assess the relationship between R2* and clinical presentations.ResultsR2* was lower in some white matter regions, including the bilateral superior longitudinal fascicle and sagittal stratum, in the iNPH group compared to the HC group. The voxel-based quantitative susceptibility mapping results did not differ between the groups. The atlas-based group comparisons yielded negative mean susceptibility values in almost all brain regions, indicating no clear paramagnetic iron deposition in the white matter of any subject. R2* and cognitive performance scores between the left superior longitudinal fasciculus (SLF) and right sagittal stratum (SS) were positively correlated. In addition to that, R2* and gait disturbance scores between left SS were negatively correlated.ConclusionOur analysis highlights the microstructural changes without iron deposition in the SLF and SS, and their association with cognitive impairment and gait disturbance in patients with iNPH

Utility of immune checkpoint inhibitors in non-small-cell lung cancer patients with poor performance status

Most clinical trials of non-small-cell lung cancer (NSCLC) exclude patients with poor ECOG performance status (PS). Thus, the efficacy of immune checkpoint inhibitors (ICIs) in patients with poor PS remains unclear. Herein, we used data from a retrospective cohort to assess the potential clinical benefits of ICIs in NSCLC patients with poor PS. Data from NSCLC patients who received ICI monotherapy at 9 institutions between December 2015 and May 2018 were retrospectively analyzed. After excluding 4 patients who lacked PS data, a total of 527 ICI-treated patients, including 79 patients with PS 2 or higher, were used for our analyses. The progression-free survival (PFS) and overall survival (OS) of patients with PS 2 or higher were significantly shorter compared with those of PS 0-1 patients (median PFS, 4.1 vs 2.0 months;P < .001 and median OS, 17.4 vs 4.0 months;P < .001). Among NSCLC patients with programmed cell death protein-ligand 1 (PD-L1) expression of 50% or higher who were treated with pembrolizumab as first-line therapy, the median PFS times of patients with PS 2 and 0-1 were 7.3 and 8.1 months, respectively. There was no significant difference in PFS between patients with PS 2 and 0-1 (P = .321). Although poor PS was significantly associated with worse outcomes in NSCLC patients treated with ICIs, pembrolizumab as a first-line treatment in NSCLC patients expressing high levels of PD-L1 could provide a clinical benefit, even in patients with PS 2

本学学生の体力水準と評価方法に関する研究 : 平成6年度 健康・栄養専攻 女子学生を対象として

The purpose of the present study is to clarify phyisical fitness level of Musashigaoka College female students. The subjects of the study were 129 female freshman students enrolled in general health and physical education classes. The subjects took fitness tests(grip strength, back strength, vertical jump, sidestep test, standing trunk flexion, trunk extension, and step test). The basic statistical analysis was examined. No significant difference was found between the results of the present study and standards of Japanese students

発症早期ALS患者に対する超高用量メチルコバラミンの有効性・安全性について : ランダム化比較試験

Importance: Post hoc analysis in a phase 2/3 trial indicated ultra-high dose methylcobalamin slowed decline of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score at week 16 as well as at week 182, without increase of adverse events, in patients with amyotrophic lateral sclerosis (ALS) who were enrolled within 1 year from onset. Objective: To validate the efficacy and safety of ultra-high dose methylcobalamin for patients with ALS enrolled within 1 year of onset. Design: A multicenter, placebo-controlled, double-blind, randomized phase 3 trial with 12-week observation and 16-week randomized period, conducted from October 2017 to September 2019. Setting: Twenty-five neurology centers in Japan. Participants: Patients with ALS diagnosed within 1 year of onset by the updated Awaji criteria were initially enrolled. Of those, patients fulfilling the following criteria after 12-week observation were eligible for randomization: 1- or 2-point decrease in ALSFRS-R total score, a percent forced vital capacity over 60%, no history of noninvasive respiratory support and tracheostomy, and being ambulant. The target number was 64 in both methylcobalamin and placebo groups. Of 203 patients enrolled in the observation, 130 patients (age, 61.0 ± 11.7 years; female, 56) met the criteria and were randomly assigned through an electronic web-response system to methylcobalamin or placebo (65 for each). Of these, 129 patients were eligible for the full analysis set, and 126 completed the double-blind stage. Interventions: Intramuscular injection of methylcobalamin 50 mg or placebo twice weekly for 16 weeks. Main outcomes and measures: The primary endpoint was change in ALSFRS-R total score from baseline to week 16 in the full analysis set. Results: The least-squares mean difference in ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin than placebo (−2.66 versus −4.63; 95% CI, 0.44–3.50; P = 0.012). The incidence of adverse events was similar between the two groups. Conclusions and relevance: Ultra-high dose methylcobalamin was efficacious in slowing functional decline and safe in the 16-week treatment period in ALS patients in the early stage and with moderate progression rate. Trial registration: UMIN-CTR Identifier: UMIN000029588 (umin.ac.jp/ctr); ClinicalTrials.gov Identifier: NCT03548311 (clinicaltrials.gov

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10−8). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10−4). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10−11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS

A comprehensive validation of very early rule-out strategies for non-ST-segment elevation myocardial infarction in emergency departments:protocol for a multicentre prospective cohort study

Introduction: Recent advances in troponin sensitivity enabled early and accurate judgement of ruling-out myocardial infarction, especially non-ST elevation myocardial infarction (NSTEMI) in emergency departments (EDs) with development of various prediction-rules and high-sensitive-troponin-based strategies (hs-troponin). Reliance on clinical impression, however, is still common, and it remains unknown which of these strategies is superior. Therefore, our objective in this prospective cohort study is to comprehensively validate the diagnostic accuracy of clinical impression-based strategies, prediction-rules and hs-troponin-based strategies for ruling-out NSTEMIs. Methods and analysis: In total, 1500 consecutive adult patients with symptoms suggestive of acute coronary syndrome will be prospectively recruited from five EDs in two tertiary-level, two secondary-level community hospitals and one university hospital in Japan. The study has begun in July 2018, and recruitment period will be about 1 year. A board-certified emergency physician will complete standardised case report forms, and independently perform a clinical impression-based risk estimation of NSTEMI. Index strategies to be compared will include the clinical impression-based strategy; prediction rules and hs-troponin-based strategies for the following types of troponin (Roche Elecsys hs-troponin T; Abbott ARCHITECT hs-troponin I; Siemens ADVIA Centaur hs-troponin I; Siemens ADVIA Centaur sensitive-troponin I). The reference standard will be the composite of type 1 MI and cardiac death within 30 days after admission to the ED. Outcome measures will be negative predictive value, sensitivity and effectiveness, defined as the proportion of patients categorised as low risk for NSTEMI. We will also evaluate inter-rater reliability of the clinical impression-based risk estimation. Ethics and dissemination: The study is approved by the Ethics Committees of the Kyoto University Graduate School and Faculty of Medicine and of the five hospitals where we will recruit patients. We will disseminate the study results through conference presentations and peer-reviewed journals