Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review

Proteinase-activated receptor 2 (PAR2) is a cell surface receptor activated by serine proteinases or specific synthetic compounds. Interest in PAR2 as a pharmaceutical target for various diseases is increasing. Here we asked two questions relevant to endothelial dysfunction and diabetes: How is PAR2 function affected in blood vessels? What role does PAR2 have in promoting obesity, diabetes, and/or metabolic syndrome, specifically via the endothelium and adipose tissues? We conducted a systematic review of the published literature in PubMed and Scopus (July 2015; search terms: par2, par-2, f2lr1, adipose, obesity, diabetes, and metabolic syndrome). Seven studies focused on PAR2 and vascular function. The obesity, diabetes, or metabolic syndrome animal models differed amongst studies, but each reported that PAR2-mediated vasodilator actions were preserved in the face of endothelial dysfunction. The remaining studies focused on nonvascular functions and provided evidence supporting the concept that PAR2 activation promoted obesity. Key studies showed that PAR2 activation regulated cellular metabolism, and PAR2 antagonists inhibited adipose gain and metabolic dysfunction in rats.We conclude that PAR2 antagonists for treatment of obesity indeed show early promise as a therapeutic strategy; however, endothelial-specific PAR2 functions, which may offset mechanisms that produce vascular dysfunction in diabetes, warrant additional study

Immune-mediated hematopoietic failure after allogeneic hematopoietic stem cell transplantation: A common cause of late graft failure in patients with complete donor chimerism

13301甲第4644号博士（医学）金沢大学博士論文要旨Abstract 以下に掲載：Biology of Blood and Marrow Transplantation 24(1) pp.43-49 2018. Elsevier. 共著者：Maruyama K, Aotsuka N, Kumano Y, Sato N, Kawashima N, Onda Y, Maruyama H, Katagiri T, Zaimoku Y, Nakagawa N, Hosomichi K, Ogawa S, Nakao

EEG resting-state networks in Alzheimer’s disease associated with clinical symptoms

Alzheimer’s disease (AD) is a progressive neuropsychiatric disease affecting many elderly people and is characterized by progressive cognitive impairment of memory, visuospatial, and executive functions. As the elderly population is growing, the number of AD patients is increasing considerably. There is currently growing interest in determining AD’s cognitive dysfunction markers. We used exact low-resolution-brain-electromagnetic-tomography independent-component-analysis (eLORETA-ICA) to assess activities of five electroencephalography resting-state-networks (EEG-RSNs) in 90 drug-free AD patients and 11 drug-free patients with mild-cognitive-impairment due to AD (ADMCI). Compared to 147 healthy subjects, the AD/ADMCI patients showed significantly decreased activities in the memory network and occipital alpha activity, where the age difference between the AD/ADMCI and healthy groups was corrected by linear regression analysis. Furthermore, the age-corrected EEG-RSN activities showed correlations with cognitive function test scores in AD/ADMCI. In particular, decreased memory network activity showed correlations with worse total cognitive scores for both Mini-Mental-State-Examination (MMSE) and Alzheimer’s Disease-Assessment-Scale-cognitive-component-Japanese version (ADAS-J cog) including worse sub-scores for orientation, registration, repetition, word recognition and ideational praxis. Our results indicate that AD affects specific EEG-RSNs and deteriorated network activity causes symptoms. Overall, eLORETA-ICA is a useful, non-invasive tool for assessing EEG-functional-network activities and provides better understanding of the neurophysiological mechanisms underlying the disease

Clinical significance and origin of leukocytes that lack HLA-A allele expression in patients with acquired aplastic anemia

To gain insight into the origin and clinical significance of leukocytes that lack human leukocyte antigen A (HLA-A) allele expression caused by a copy-number-neutral loss of heterozygosity in the short arm of chromosome 6 in patients with acquired aplastic anemia (AA), we used a high-sensitivity flow cytometry assay to investigate the presence of HLA-A allele-lacking leukocytes (HLA-LLs) in 144 AA patients. HLA-LLs, accounting for 0.2–99.8% of each leukocyte population, were detected in 18 of 71 (25.4%) newly diagnosed patients and in 25 of 73 (34.2%) previously treated patients. The lineage combination patterns of the HLA-LLs in the 43 HLA-LL+ patients were granulocytes (Gs), monocytes (Ms), B cells (Bs), and T cells (Ts; GMBT) in 13 cases, GMB in 16 cases, GM in 11 cases, and B alone in three cases. The response rate to antithymocyte globulin plus cyclosporine therapy (100%) and the 2-year, failure-free survival rate (100%) in 8 newly diagnosed HLA-LL+ patients were significantly higher than in 23 HLA-LL− patients (52.2% for both). These data suggest that HLA-LLs are a useful marker of the presence of immune pathophysiology in AA and that T-cell attacks against hematopoietic progenitor cells, rather than against hematopoietic stem cells, can trigger bone marrow failure in AA patients. © 2016 ISEH - International Society for Experimental HematologyEmbargo Period 12 month

Therapy for CKD-associated muscle dysfunction

Background Chronic kidney disease (CKD) patients experience skeletal muscle wasting and decreased exercise endurance. Our previous study demonstrated that indoxyl sulfate (IS), a uremic toxin, accelerates skeletal muscle atrophy. The purpose of this study was to examine the issue of whether IS causes mitochondria dysfunction and IS-targeted intervention using AST-120, which inhibits IS accumulation, or mitochondria-targeted intervention using L-carnitine or teneligliptin, a dipeptidyl peptidase-4 inhibitor which retains mitochondria function and alleviates skeletal muscle atrophy and muscle endurance in chronic kidney disease mice. Methods The in vitro effect of IS on mitochondrial status was evaluated using mouse myofibroblast cells (C2C12 cell). The mice were divided into sham or 5/6-nephrectomized (CKD) mice group. Chronic kidney disease mice were also randomly assigned to non-treatment group and AST-120, L-carnitine, or teneligliptin treatment groups. Results In C2C12 cells, IS induced mitochondrial dysfunction by decreasing the expression of PGC-1α and inducing autophagy in addition to decreasing mitochondrial membrane potential. Co-incubation with an anti-oxidant, ascorbic acid, L-carnitine, or teneligliptine restored the values to their original state. In CKD mice, the body and skeletal muscle weights were decreased compared with sham mice. Compared with sham mice, the expression of interleukin-6 and atrophy-related factors such as myostatin and atrogin-1 was increased in the skeletal muscle of CKD mice, whereas muscular Akt phosphorylation was decreased. In addition, a reduced exercise capacity was observed for the CKD mice, which was accompanied by a decreased expression of muscular PCG-1α and increased muscular autophagy, as reflected by decreased mitochondria-rich type I fibres. An AST-120 treatment significantly restored these changes including skeletal muscle weight observed in CKD mice to the sham levels accompanied by a reduction in IS levels. An L-carnitine or teneligliptin treatment also restored them to the sham levels without changing IS level. Conclusions Our results indicate that IS induces mitochondrial dysfunction in skeletal muscle cells and provides a potential therapeutic strategy such as IS-targeted and mitochondria-targeted interventions for treating CKD-induced muscle atrophy and decreased exercise endurance

東京湾内湾に造成された砂浜海岸と泥質干潟の魚類相と多様性

東京湾内湾に造成された海浜と干潟が魚類にどのような場を提供しているのか明らかにすることを目的として、月に一度の小型地曳網による調査を5年間行った。調査地点は東京都大田区の「大森ふるさとの浜辺公園」で、同公園は海浜（1.2 ha）と干潟（1.0 ha）、それらの間に浅場（4.6 ha）の海域を有する公園である。周辺は水深約5 mの運河域であるが、運河域との境界に海底から高さ約4 mの砂留潜堤が造成されたため、浅場の水深は最も深い部分で1.5 m程度となっている。採集された魚類は海浜で19科40種60,050個体、干潟で19科38種44,807個体であった。2地点の底質には違いがみられたが、出現する種数や個体数、または生活史型や利用様式から魚類相はほぼ同様であった。本調査地点はハゼ科河口魚が優占し、またそれらのハゼ科河口魚には仔魚から成魚までの長期的な成育場を提供していることが明らかとなった。しかし、運河域の最奥に立地していることから、海水魚の出現は少なかった。また、多摩川河口域の3つの干潟と多様度の比較を行うと、本調査地点は劣ることが明らかとなった。The Furuhama Park, which was artificially improved and developed in 2000 at Heiwajima artificial island of Ota City, is located at the innermost part of Tokyo Bay. The Park is composed of the sandy beach (1.2 ha) and tidal flat (1.0 ha) with a shallow water area (4.6ha) between them, and separated from the outside canal by submerged dikes. Monthly samplings of fishes were carried out in both the sandy beach and tidal flat by using the small seine-net from May 2014 to April 2019. A total of 60,050 individuals of 40 species of 19 families and 44,807 individuals of 38 species of 19 families were collected from the sandy beach and tidal flat, respectively. Despite a difference was confirmed in the bottom sediment between the sandy beach and tidal flat, no remarkable differences were detected on the fish fauna. Comparisons with previous studies conducted at natural habitats in the inner Tokyo Bay revealed that the fish diversity of the Park were inferior to natural tidal flats. Our study suggests that the Park provides various habitats for estuarine gobiids, but the location of the Park secluded from the open sea through canals is likely to be unsuitable for marine fish habitats.丸山啓太・河野博: 東京海洋大学魚類学研究室Keita MARUYAMA(Corresponding author) and Hiroshi KOHNO: Laboratory of Ichthyology, Tokyo Univercity of Marine Science and Technology(TUMSAT)河野博: 東京海洋大学学術研究院海洋環境科学部門Hiroshi KOHNO: Department of Ocean Sciences, Tokyo University of Marine Science and Technology (TUMSAT)竹山佳奈・中瀬浩太: 五洋建設株式会社環境事業部Kana TAKEYAMA and Kota NAKASE: Penta-ocean Construction Co., Lt

Financial Issues of Higher Education: Marketization of Funding Resources: Proceedings of the 45th R.I.H.E. Annual Study Meeting

This report is a summary of the 45th Research Institute for Higher Education Annual Study Meeting, held at the Higashi-Hiroshima campus of Hiroshima University in 2017. The theme of the year was “Financial Issues of Higher Education – Marketization of Funding Resources”. Takafumi Goda, President of Shokei Gakuin University, opened proceedings with an inaugural speech entitled “Restructuring of higher education finance”. Subsequently, three speakers made presentations, followed by comments and discussion. Japanese universities are at a significant turning point regarding their management as financial assistance to higher education is being reduced. More specifically, the basic research funding available from the central government is being reduced, and universities increasingly have to apply for competitive research funding. As a result, the sum total of scientific research funds has increased, but the drop in the relative international position of Japanese research activities is brought into question. At this Annual Study Meeting, we learned about the policy and circumstances of higher education finance from a leading expert in the field and discussed what form of resource allocation was most desirable.はしがき … 大膳 司 i 研究員集会の趣旨 … iii 趣旨説明の補足－高等教育の市場化政策・財政規模・補助金による国立大学の分化－ … 藤村 正司 1 基調講演 　高等教育財政の構造改革に向けて－なぜ混迷が深まるのか－ … 合田 隆史 9 　セッション1の司会を担当して … 藤村 正司 29 論点提起 　アメリカの研究大学の資源配分 … 阿曽沼 明裕 33 　米国州政府による大学評価に基づく資源配分 … 吉田 香奈 43 　競争的資源配分と教育・研究の歪みについて－学術的価値生産関数の効率性の観点から－ … 吉田 浩 55 　第45回研究員集会「セッション2−論点提起−」を司会して … 濱中 義隆 69 　第45回研究員集会セッション2－論点提起－を司会して … 二宮 祐 73 コメントとディスカッション 　コメント … 金子 元久 77 　セッション3 の議論から … 浦田 広明 83 　高等教育の財政問題 司会を担当して … 丸山 文裕 87 　研究員集会の概要 … 9

佐世保市民における食育の認知及び実践

佐世保市では平成18年に｢佐世保市食育推進計画｣を策定し､食育に取り組んできた｡本報告では平成18年からの5か年で佐世保市民の食育に関する知識や食生活がどのように変化したのかを平成22年9月に行った｢食育に関するｱﾝｹｰﾄ調査｣の結果を基に検討し､今後の食育推進における資料を得ることを目的とした｡食育に関する知識は平成18年と比較すると広く普及していたが､食生活の改善に結びついていない項目も多くみられた｡また､食生活の改善には食育の取り組みを行うという意識を持つことが最も重要であることが示されたが､食育に関する知識がない者も正しい知識を得ることで､改善する可能性が示された｡以上のことより､佐世保市においては今後も継続した食育の推進を図ることが必要であり､食生活の改善のためには､食育に取り組むことを目指すだけでなく､食育に関する正しい知識の普及が重要であることが示された｡“Sasebo Food Education Promotion Plan”was designed in 2006 in Sasebo city and then incorporated into food education. Subsequently, after 5 years, a“questionnaire survey related to food education”was conducted in September 2010 in order to examine whether there was a change in the dietary habits and dietary knowledge of the residents of Sasebo city. The objective of the present report was to obtain a future data regarding the promotion of food education on the basis of the results of the questionnaire administered in 2010.The information about food education is spreading widely now, as compared to 2006. However, many instances not related to the improvement of dietary habits were found. Moreover, it was indicated that in order to improve dietary habits, one has to be aware of incorporating the food education plan in his or her life, but the right dietary knowledge should be provided to people who do not have any knowledge regarding this.Therefore, in future, a plan for continuous promotion of food education should be designed in Sasebo city, and it should not only be incorporated in food education, but the right information should be imparted in order to improve the dietary habits

佐世保市の食育に関するｱﾝｹｰﾄ調査報告(学齢期)

近年の子どもたちを取り巻く社会環境においては､朝食欠食や偏食等にみられるような不規則な食生活など､様々な問題が提起されている1-4)｡平成17年に食育基本法が公布され､佐世保市においても､平成18年度に｢佐世保市食育推進計画｣(平成18年度～平成22年度)6) を作成し､食育の推進に努めてきた｡この食育推進計画における目標値の達成状況を把握するために｢食育に関するｱﾝｹｰﾄ調査｣7) を行った｡本報告においては､特に学齢期の子どもを対象とした調査結果および数値目標との比較を行った｡その結果､計画策定時の状態よりも改善されている事項が多く､食育推進の取組の効果があった｡ただし､目標値にまだ達していないことから､今後も継続した食育推進の取組が必要であり､それには､家庭や教育機関､社会など環境が関与する必要があることが示唆された｡Children in recent years are irregular eating habits in breakfast skipping a meal or an unbalanced diet, and have become a social problem. The basic law on nutritional education was proclaimed in 2005, the Sasebo food education promotion plan was drawn up also in Sasebo in 2006, and it has striven for promotion of food education. In this food education promotion plan, the questionnaire about food education was performed to the original investigation, and the progress which is a plan was checked. Especially this report compared results of an investigation and a desired value for the school age child. As a result, there were many improving points as an effect of a food education promotion plan. However, since a desired value has not been reached yet, the continued food education promotion is required. And it was suggested to goal achievement that the influence of a home, educational facilities, and society is a theme