The incidence of diabetes among the non-diabetic residents in Kawauchi village, Fukushima, who experienced evacuation after the 2011 Fukushima Daiichi nuclear power plant disaster

OBJECTIVES: After the Fukushima Daiichi nuclear power plant disaster in 2011, residents of Kawauchi village who experienced evacuation had a high risk of suffering from diabetes and metabolic syndrome compared with non-evacuees. In addition to evacuation, lifestyle characteristics can be important factors influencing the development and prognosis of diabetes or glucose tolerance. The current study aimed to evaluate the effects of evacuation (i.e., lifestyle changes) on the incidence of diabetes among the non-diabetic residents of Kawauchi village. METHODS: Design is retrospective cohort study. Annual health examination data of residents of Kawauchi village and control area (Ono town) in Fukushima prefecture from 2008 to 2017, as available from the Japanese National Health Insurance system. Participants were classified into three groups: "Diabetes (DM)" (FBG ≥ 126 mg/dL or HbA1c ≥ 6.5% or hospital visit for DM or usage of diabetic medication), "Borderline DM" (126 mg/dL > FBG ≥ 110 mg/dL or 6.5% > HbA1c ≥ 6.0%, and without hospital visit, and without diabetic medication), and "Normoglycemic" (FBG < 110 mg/dL and HbA1c < 6.0%, and without hospital visit, and without diabetic medication). New onset of diabetes was evaluated and the events or missing data were occurred at health checkup. For this survival analysis, 339 residents in Kawauchi and 598 residents in Ono were included. Average follow-up periods after 2010 were 3.9 years in Kawauchi village and 3.6 years in Ono town. RESULTS: Compared with the normoglycemic group, incidence of DM was much greater in the borderline DM group, where DM occurred among 38.2% of the group in 2012 and increased to over 60% cumulatively through 2017 in Kawauchi village. DM had a prevalence of 16.3% in 2012, and below 30% in 2017 in borderline DM group of Ono town. Cox proportional hazard regression analysis was applied to non-DM groups at both study sites separately to evaluate the effects of lifestyle changes at each site. While BMI, BMI change, and the lack of regular exercise (HR = 1.29, 1.72, and 5.04, respectively) showed significant associations with the onset of diabetes in Ono town, only BMI and late-night dinner (HR = 1.21 and 4.86, respectively) showed significant associations with diabetes onset in Kawauchi village. CONCLUSIONS: The current results confirmed that diabetes incidence was increased 6 years after the Daiichi nuclear power plant disaster in Kawauchi. We also found changes in lifestyle habits, suggesting that diabetes prevention with promotion of healthy lifestyle behaviors is an urgent priority

Seminolipid and its precursor/degradative product, galactosylalkylacylglycerol, in the testis of saposin A- and prosaposin-deficient mice

Sphingolipid activator proteins (saposins A, B, C, and D) are derived from a common precursor protein (prosaposin) and specifically activate in vivo degradation of glycolipids with short carbohydrate chains. A mouse model of prosaposin deficiency (prosaposi

Liganded Thyroid Hormone Receptor Inhibits Phorbol 12-O-Tetradecanoate-13-Acetate-Induced Enhancer Activity via Firefly Luciferase cDNA

Thyroid hormone receptor (TR) belongs to the nuclear hormone receptor (NHR) superfamily and regulates the transcription of its target genes in a thyroid hormone (T3)-dependent manner. While the detail of transcriptional activation by T3 (positive regulation) has been clarified, the mechanism of T3-dependent repression (negative regulation) remains to be determined. In addition to naturally occurring negative regulations typically found for the thyrotropin β gene, T3-bound TR (T3/TR) is known to cause artificial negative regulation in reporter assays with cultured cells. For example, T3/TR inhibits the transcriptional activity of the reporter plasmids harboring AP-1 site derived from pUC/pBR322-related plasmid (pUC/AP-1). Artificial negative regulation has also been suggested in the reporter assay with firefly luciferase (FFL) gene. However, identification of the DNA sequence of the FFL gene using deletion analysis was not performed because negative regulation was evaluated by measuring the enzymatic activity of FFL protein. Thus, there remains the possibility that the inhibition by T3 is mediated via a DNA sequence other than FFL cDNA, for instance, pUC/AP-1 site in plasmid backbone. To investigate the function of FFL cDNA as a transcriptional regulatory sequence, we generated pBL-FFL-CAT5 by ligating FFL cDNA in the 5' upstream region to heterologous thymidine kinase promoter in pBL-CAT5, a chloramphenicol acetyl transferase (CAT)-based reporter gene, which lacks pUC/AP-1 site. In kidney-derived CV1 and choriocarcinoma-derived JEG3 cells, pBL-FFL-CAT5, but not pBL-CAT5, was strongly activated by a protein kinase C activator, phorbol 12-O-tetradecanoate-13-acetate (TPA). TPA-induced activity of pBL-FFL-CAT5 was negatively regulated by T3/TR. Mutation of nt. 626/640 in FFL cDNA attenuated the TPA-induced activation and concomitantly abolished the T3-dependent repression. Our data demonstrate that FFL cDNA sequence mediates the TPA-induced transcriptional activity, which is inhibited by T3/TR

SUMOylation of DISC1: a potential role in neural progenitor proliferation in the developing cortex

DISC1 is a multifunctional, intracellular scaffold protein. At the cellular level, DISC1 plays a pivotal role in neural progenitor proliferation, migration, and synaptic maturation. Perturbation of the biological pathways involving DISC1 is known to lead to behavioral changes in rodents, which supports a clinical report of a Scottish pedigree in which the majority of family members with disruption of the DISC1 gene manifest depression, schizophrenia, and related mental conditions. The discrepancy between modest evidence in genetics and strong biological support for the role of DISC1 in mental conditions suggests a working hypothesis that regulation of DISC1 at the protein level, such as posttranslational modification, may play a role in the pathology of mental conditions. In this study, we report on the SUMOylation of DISC1. This posttranslational modification occurs on lysine residues where the small ubiquitin-related modifier (SUMO) and its homologs are conjugated to a large number of cellular proteins, which in turn regulates their subcellular distribution and protein stability. By using in silico, biochemical, and cell-biological approaches, we now demonstrate that human DISC1 is SUMOylated at one specific lysine 643 (K643). We also show that this residue is crucial for proper neural progenitor proliferation in the developing cortex

Targeted expression of stepfunction opsins in transgenic rats for optogenetic studies

Abstract Rats are excellent animal models for experimental neuroscience. However, the application of optogenetics in rats has been hindered because of the limited number of established transgenic rat strains. To accomplish cell-type specific targeting of an optimized optogenetic molecular tool, we generated ROSA26/CAG-floxed STOP-ChRFR(C167A)-Venus BAC rats that conditionally express the step-function mutant channelrhodopsin ChRFR(C167A) under the control of extrinsic Cre recombinase. In primary cultured cortical neurons derived from this reporter rat, only Cre-positive cells expressing ChRFR(C167A) became bi-stable, that is, their excitability was enhanced by blue light and returned to the baseline by yellow~red light. In bigenic pups carrying the Phox2B-Cre driver, ChRFR(C167A) was specifically expressed in the rostral parafacial respiratory group (pFRG) in the medulla, where endogenous Phox2b immunoreactivity was detected. These neurons were sensitive to blue light with an increase in the firing frequency. Thus, this transgenic rat actuator/reporter system should facilitate optogenetic studies involving the effective in vivo manipulation of the activities of specific cell fractions using light of minimal intensity

創造性を育成するための看護教育方法の開発(その1) : 創造性看護教育に関する海外研修レポート

報告Report2006年9月、共同研究「創造性を育成するための看護教育方法の開発」の一環としての韓国研修の機会を得た。今回の研修の目的は、研究を進めるにあたって、研究対象の1つである韓国における研究計画の実現可能性の確認と具体的な打ち合わせを行うことであった。病院見学をはじめ、嶺南(ヨンナム)理工大学看護学科教員との交流セッション、嶺南大学の大学院生とのラベルワークの実施を通して、両国の看護教育に対する理解を深めるとともに、われわれの研究に対する理解と協力を得ることができた。さらに研究の具体的計画の実現可能性の確認できた。また、共同研究者である朴教授と綿密な打ち合わせもでき、研究を発展させるための方向性と課題を明確にすることができた。その成果を報告する

GATA2 Mediates Thyrotropin-Releasing Hormone-Induced Transcriptional Activation of the Thyrotropin β Gene

Thyrotropin-releasing hormone (TRH) activates not only the secretion of thyrotropin (TSH) but also the transcription of TSHβ and α-glycoprotein (αGSU) subunit genes. TSHβ expression is maintained by two transcription factors, Pit1 and GATA2, and is negatively regulated by thyroid hormone (T3). Our prior studies suggest that the main activator of the TSHβ gene is GATA2, not Pit1 or unliganded T3 receptor (TR). In previous studies on the mechanism of TRH-induced activation of the TSHβ gene, the involvements of Pit1 and TR have been investigated, but the role of GATA2 has not been clarified. Using kidney-derived CV1 cells and pituitary-derived GH3 and TαT1 cells, we demonstrate here that TRH signaling enhances GATA2-dependent activation of the TSHβ promoter and that TRH-induced activity is abolished by amino acid substitution in the GATA2-Zn finger domain or mutation of GATA-responsive element in the TSHβ gene. In CV1 cells transfected with TRH receptor expression plasmid, GATA2-dependent transactivation of αGSU and endothelin-1 promoters was enhanced by TRH. In the gel shift assay, TRH signal potentiated the DNA-binding capacity of GATA2. While inhibition by T3 is dominant over TRH-induced activation, unliganded TR or the putative negative T3-responsive element are not required for TRH-induced stimulation. Studies using GH3 cells showed that TRH-induced activity of the TSHβ promoter depends on protein kinase C but not the mitogen-activated protein kinase, suggesting that the signaling pathway is different from that in the prolactin gene. These results indicate that GATA2 is the principal mediator of the TRH signaling pathway in TSHβ expression