FTY720 Reduces Lipid Accumulation by Upregulating ABCA1 through Liver X Receptor and Sphingosine Kinase 2 Signaling in Macrophages

Formation of foam cells as a result of excess lipid accumulation by macrophages is a pathological hallmark of atherosclerosis. Fingolimod (FTY720) is an immunosuppressive agent used in clinical settings for the treatment of multiple sclerosis and has been reported to inhibit atherosclerotic plaque development. However, little is known about the effect of FTY720 on lipid accumulation leading to foam cell formation. In this study, we investigated the effects of FTY720 on lipid accumulation in murine macrophages. FTY720 treatment reduced lipid droplet formation and increased the expression of ATP-binding cassette transporter A1 (ABCA1) in J774 mouse macrophages. FTY720 also enhanced the expression of liver X receptor (LXR) target genes such as FASN, APOE, and ABCG1. In addition, FTY720-induced upregulation of ABCA1 was abolished by knockdown of sphingosine kinase 2 (SphK2) expression. Furthermore, we found that FTY720 treatment induced histone H3 lysine 9 (H3K9) acetylation, which was lost in SphK2-knockdown cells. Taken together, FTY720 induces ABCA1 expression through SphK2-mediated acetylation of H3K9 and suppresses lipid accumulation in macrophages, which provides novel insights into the mechanisms of action of FTY720 on atherosclerosis

Study of Sumida River, Part 2: Analysis of Identification of COD and EC Characteristics in Fall 2021

The Sumida River streamside makes up a part of the Kitasenjyu campus at Teikyo University of Science(TUS). It is essential for university students and faculty members to learn its environmental and chemical characteristics from the viewpoint of environmental education. A water analysis of the Sumida River was conducted in the fall season (Fall 2021) at 10 locations around the Kitasenjyu campus, along with a 24-hour continuous survey in front of the No. 7 building. The fall analysis was performed using the same procedure as the previous analysis in spring (Spring 2021). The conclusions we reached are as follows: 1) Discharge water from the Mikawagima wastewater purification facility (WPF) was found to be the primary source of chemical contamination in the study area, causing an increase in COD (chemical oxygen demand). Upstream, Miyagi WPF was presumed to be the primary source of the chemical contamination. 2) The discharged high COD water from these WPFs was diffused by the tidal movement of Tokyo Bay and then was homogenized in the study area. 3) From our survey on the streaming motion of the Sumida River and public COD data from the Tokyo metropolitan government, we redefined the boundary between high and low COD zones set under the Agastuma Bridge. 4) Urethane foam with photocatalysis material of TiO2 was synthesized as a novel wastewater treatment material. As it displayed good decomposition characteristics oforganic material in tested water, porous and robust materials with TiO2 for continuous outdoor use should be investigated to achieve practical applications shortly

Study of Sumida River, Part-1; Its COD and EC characteristics from data collected in spring, 2021

The Sumida River, a typical urban river in Tokyo, has been recognized as a site for fostering Tokyo’s urbanlife that serves as a venue of leisure and relaxation for its residents. As the Teikyo University of Science(TUS) is located near the Sumida River, students spend a lot of time nearby. Clarifying the characteristics ofSumida River, and teaching it to students, are important not only for enhancing environmental awarenessamong students, but also local environment conservation. In this study, chemical oxygen demand (COD)and electric conductivity (EC) data, major sources of contamination, and the characteristics of the river wereanalyzed and interpreted as follows. 1) Although our COD and EC data showed that Sumida River wasaffected by tidal movement, the river water in our research area (from Otakebashi Bridge to Senju-OhashiBridge) might exhibit backward and forward movements, and it was slightly affected by sea water from theTokyo Bay. 2) Major chemical contaminant sources of investigated area were determined to be the Miyagiwastewater purification facility (WPF) and the Mikawajima WPF at the upstream and downstream sides ofthe TUS, respectively. 3) We presume a two-fraction zone in the Sumida River from our analytical resultsand public data, including a "high COD zone" with an upstream stagnant zone upper the Shirahige Bridge,and a "low COD zone" with a downstream flush zone under the Shirahige Bridge. Raising environmentalawareness concerning the urban river among its residents presumably might contribute to maintaining itsclean and safe environment. We came to conclusion that the importance of educating the citizens aboutkeeping urban rivers environmentally clean and safe for the future generations

Psychosocial factors at work and inflammatory markers: protocol for a systematic review and meta-analysis

Introduction Chronic inflammation may be a mediator for the development of cardiovascular disease (CVD), metabolic diseases and psychotic and neurodegenerative disorders. Meta-analytic associations between work-related psychosocial factors and inflammatory markers have shown that work-related psychosocial factors could affect the flexibility and balance of the immune system. However, few systematic reviews or meta-analyses have investigated the association between work-related psychosocial factors and inflammatory markers. Based on prospective studies, the present investigation will conduct a comprehensive systematic review and meta-analysis of the association between work-related psychosocial factors and inflammatory markers.Methods and analysis The systematic review and meta-analysis will include published studies identified from electronic databases (PubMed, EMBASE, PsycINFO, PsycARTICLES, Web of Science and Japan Medical Abstracts Society) according to recommendations of the Meta-analysis of Observational Studies in Epidemiology guideline. Inclusion criteria are studies that: examined associations between work-related psychosocial factors and increased inflammatory markers; used longitudinal or prospective cohort designs; were conducted among workers; provided sufficient data for calculating ORs or relative risk with 95% CIs; were published as original articles in English or Japanese; and were published up to the end of 2017. Study selection, data extraction, quality assessment and statistical syntheses will be conducted by 14 investigators. Any inconsistencies or disagreements will be resolved through discussion. The quality of studies will be evaluated using the Risk of Bias Assessment Tool for Non-randomized Studies.Ethics and dissemination The investigation study will be based on published studies, so ethics approval is not required. The results of this study will be submitted for publication in a scientific peer-reviewed journal. The findings may be useful for assessing risk factors for increased inflammatory markers in the workplace and determining future approaches for preventing CVD, metabolic diseases and psychotic and neurodegenerative disorders

看護基礎教育におけるActive Learningの手法を用いた公衆衛生学教育の試み（第3報）

本研究は、A 大学看護学部の看護基礎教育で実施されたActive Leaning の手法を用いた公衆衛生学の演習プログラムにおける学生の学びを明らかにすることを目的とした。対象は、A 大学看護学部の学士課程に在籍する２年次の学生であり、演習は、大学に対する「大学内禁煙対策に対する政策提言」を目指し、３年間を一纏まりとして計画され、３年目の演習では、大学内の禁煙対策で使用できるパンフレットを作成した。その結果、学生は「公衆衛生入門で学んだ地域の特性、生活環境特性から対象に必要なケアを見出し、予防的行動を促すという視点は、病棟看護師にも必要なものである」などの学びを得ていた。また、本演習を通し看護学部と保健センターが連携したことで、大学内で防煙・卒煙の取り組み等が行われるようになった。現実の課題を題材にActive Leaning の手法を用いた本稿の試みは、当初の目的以上の展開を迎えたと考えられるが、その分析については今後の課題である

Neurotensin Receptor 1 Gene (NTSR1) Polymorphism Is Associated with Working Memory

BACKGROUND: Recent molecular genetics studies showed significant associations between dopamine-related genes (including genes for dopamine receptors, transporters, and degradation) and working memory, but little is known about the role of genes for dopamine modulation, such as those related to neurotensin (NT), in working memory. A recent animal study has suggested that NT antagonist administration impaired working memory in a learning task. The current study examined associations between NT genes and working memory among humans. METHODS: Four hundred and sixty healthy undergraduate students were assessed with a 2-back working memory paradigm. 5 SNPs in the NTSR1 gene were genotyped. 5 ANOVA tests were conducted to examine whether and how working memory differed by NTSR1 genotype, with each SNP variant as the independent variable and the average accuracy on the working memory task as the dependent variable. RESULTS: ANOVA results suggested that two SNPs in the NTSR1 gene (rs4334545 and rs6090453) were significantly associated with working memory. These results survived corrections for multiple comparisons. CONCLUSIONS: Our results demonstrated that NTSR1 SNP polymorphisms were significantly associated with variance in working memory performance among healthy adults. This result extended previous rodent studies showing that the NT deficiency impairs the working memory function. Future research should replicate our findings and extend to an examination of other dopamine modulators

Unc-51/ATG1 Controls Axonal and Dendritic Development via Kinesin-Mediated Vesicle Transport in the Drosophila Brain

Background:Members of the evolutionary conserved Ser/Thr kinase Unc-51 family are key regulatory proteins that control neural development in both vertebrates and invertebrates. Previous studies have suggested diverse functions for the Unc-51 protein, including axonal elongation, growth cone guidance, and synaptic vesicle transport.Methodology/Principal Findings:In this work, we have investigated the functional significance of Unc-51-mediated vesicle transport in the development of complex brain structures in Drosophila. We show that Unc-51 preferentially accumulates in newly elongating axons of the mushroom body, a center of olfactory learning in flies. Mutations in unc-51 cause disintegration of the core of the developing mushroom body, with mislocalization of Fasciclin II (Fas II), an IgG-family cell adhesion molecule important for axonal guidance and fasciculation. In unc-51 mutants, Fas II accumulates in the cell bodies, calyx, and the proximal peduncle. Furthermore, we show that mutations in unc-51 cause aberrant overshooting of dendrites in the mushroom body and the antennal lobe. Loss of unc-51 function leads to marked accumulation of Rab5 and Golgi components, whereas the localization of dendrite-specific proteins, such as Down syndrome cell adhesion molecule (DSCAM) and No distributive disjunction (Nod), remains unaltered. Genetic analyses of kinesin light chain (Klc) and unc-51 double heterozygotes suggest the importance of kinesin-mediated membrane transport for axonal and dendritic development. Moreover, our data demonstrate that loss of Klc activity causes similar axonal and dendritic defects in mushroom body neurons, recapitulating the salient feature of the developmental abnormalities caused by unc-51 mutations.Conclusions/Significance:Unc-51 plays pivotal roles in the axonal and dendritic development of the Drosophila brain. Unc-51-mediated membrane vesicle transport is important in targeted localization of guidance molecules and organelles that regulate elongation and compartmentalization of developing neurons

看護基礎教育におけるActive Learningの手法を用いた公衆衛生学教育の試み（第2報）

本研究は、Ａ大学看護学部の看護基礎教育で実施されたActive Leaning の手法を用いた公衆衛生学の演習プログラムの2 年目の取り組みを記述し、学生が捉えた公衆衛生学を学ぶ意義と看護職が禁煙対策に取り組む意義の2 つを明らかにすることを目的とした。対象は、2015 年度Ａ大学看護学部の学士課程に在籍した2 年次の学生であり、2 年目の演習は、大学におけるプライマリーインフォーマントとキーインフォーマントに対するインタビュー調査を実施した。その結果、学生は【看護・公衆衛生は全ての人々を対象とすることを実感する】こと、【看護学生として大学の健康増進・予防活動でできることがある】と感じることなどを公衆衛生学を学ぶ意義と捉えていた。また、看護職が禁煙対策に取り組む意義として【人々の生命を守るという看護職の使命を果たすことに繋がる】ことなどをあげており、演習が学生の主体性を高め、自身の看護観を深めることに寄与していることが示唆された

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