肺癌におけるREG Iα遺伝子の発現は、腺癌、肩平上皮癌で異なったメカニズムにより、予後不良を示唆する。

The aim of the present study was to evaluate the effects of the REG Iα and REG Iβ genes on lung cancer cell lines, and thereafter, the expression of REG family genes (REG Iα, REG Iβ, REG III, HIP/PAP and REG IV) in lung cancer in relation to patient prognosis was evaluated. Lung adenocarcinoma (AD) and squamous cell carcinoma (SCC) cell lines expressing REG Iα or REG Iβ (HLC-1 REG Iα/Iβ and EBC-1 REG Iα/Iβ) were established, and cell number, cell invasive activity, and anchorage-independent cell growth were compared with these variables in the control cells. The expression levels of REG family genes were evaluated by real-time RT-PCR in surgically resected lung cancers, and disease-specific survival (DSS) curves were generated. The HLC-1 REG Iα/Iβ cell line showed significant increases in cell number and anchorage-independent cell growth compared with the control cells. EBC-1 REG Iα/Iβ cells showed significant increases in cell invasive activity and anchorage-independent cell growth as compared with the control cells. Except for the REG Iβ gene, expression of other REG family genes was observed in the surgically resected samples; however, DSS was significantly worse only in stage I patients who were positive for REG Iα expression than in patients who were negative for REG Iα expression. The effects of REG Iα on AD and SCC cells were different in the in vitro study, and a correlation between REG Iα expression and patient prognosis was noted in the in vivo study. Therefore, overexpression of REG Iα is a risk factor for poor prognosis caused by discrete mechanisms in AD and SCC patients.博士（医学）・乙第1339号・平成26年5月28日本文のリンク：http://dx.doi.org/10.3892/or.2013.2739Copyright © Spandidos Publications 201

Seasonal changes of arsenic speciation in lake waters in relation to eutrophication

金沢大学理工研究域物質化学系In this study, the influence of eutrophication on arsenic speciation in lake waters was investigated. Surface water samples (n = 1-10) were collected from 18 lakes in Japan during July 2007 and February 2008. The lakes were classified into mesotrophic (7 lakes) and eutrophic (11 lakes) based on the total phosphate (T-P) and chlorophyll-a (Chl-a) concentrations in water column. Inorganic, methylated and ultraviolet-labile fractions of arsenic species were determined by combining hydride generation atomic absorption spectrometry with ultraviolet irradiation. Organoarsenicals (mainly methylated and ultraviolet-labile fractions) comprised 30-60% of the total arsenic in most lakes during summer. On the other hand, inorganic arsenic species (As(III + V)) dominates (about 60-85%) during winter. The occurrence of ultraviolet-labile fractions of arsenic was higher in eutrophic lakes than those in mesotrophic lakes in both seasons. The concentration of dimethyl arsenic (DMAA) was high in eutrophic lakes during winter; and in mesotrophic lakes during summer. The results suggest that the conversion of As(III + V) to more complicated organoarsenicals occurred frequently in eutrophic lakes compared to that in mesotrophic lakes, which is thought to be the influence of biological activity in the water column. The distribution of arsenic species were well correlated with phosphate concentrations than those of Chl-a. This might be due to the competitive uptake of As(V) and phosphate by phytoplankton. The organoarsenicals (OrgAs)/As(V) ratio was higher at low phosphate concentration indicating that conversion of As(V) to OrgAs species was more active in phosphate-exhausted lakes with high phytoplankton density. © 2009 Elsevier B.V. All rights reserved

Seasonal changes of arsenic speciation in lake waters in relation to eutrophication.

金沢大学理工研究域物質化学系In this study, the influence of eutrophication on arsenic speciation in lake waters was investigated. Surface water samples (n=1-10) were collected from 18 lakes in Japan during July 2007 and February 2008. The lakes were classified into mesotrophic (7 lakes) and eutrophic (11 lakes) based on the total phosphate (T-P) and chlorophyll-a (Chl-a) concentrations in water column. Inorganic, methylated and ultraviolet-labile fractions of arsenic species were determined by combining hydride generation atomic absorption spectrometry with ultraviolet irradiation. Organoarsenicals (mainly methylated and ultraviolet-labile fractions) comprised 30-60% of the total arsenic in most lakes during summer. On the other hand, inorganic arsenic species (As(III+V)) dominates (about 60-85%) during winter. The occurrence of ultraviolet-labile fractions of arsenic was higher in eutrophic lakes than those in mesotrophic lakes in both seasons. The concentration of dimethyl arsenic (DMAA) was high in eutrophic lakes during winter; and in mesotrophic lakes during summer. The results suggest that the conversion of As(III+V) to more complicated organoarsenicals occurred frequently in eutrophic lakes compared to that in mesotrophic lakes, which is thought to be the influence of biological activity in the water column. The distribution of arsenic species were well correlated with phosphate concentrations than those of Chl-a. This might be due to the competitive uptake of As(V) and phosphate by phytoplankton. The organoarsenicals (OrgAs)/As(V) ratio was higher at low phosphate concentration indicating that conversion of As(V) to OrgAs species was more active in phosphate-exhausted lakes with high phytoplankton density

妊娠高血圧症候群におけるRAGEの関与

Preeclampsia/hypertensive disorders of pregnancy (PE/HDP) is a serious and potentially life-threatening disease. Recently, PE/HDP has been considered to cause adipose tissue inflammation, but the detailed mechanism remains unknown. We exposed human primary cultured adipocytes with serum from PE/HDP and healthy controls for 24 h, and analyzed mRNA expression of several adipokines, cytokines, and ligands of the receptor for advanced glycation endproducts (RAGE). We found that the mRNA levels of interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), high mobility group box 1 (HMGB1), and RAGE were significantly increased by the addition of PE/HDP serum. Among RAGE ligands, advanced glycation endproducts (AGE) and HMGB1 increased mRNA levels of IL-6 and CCL2 in SW872 human adipocytes and mouse 3T3-L1 cells. The introduction of small interfering RNA for RAGE (siRAGE) into SW872 cells abolished the AGE- and HMGB1-induced up-regulation of IL-6 and CCL2. In addition, lipopolysaccharide (LPS), a ligand of RAGE, increased the expression of IL-6 and CCL2 and siRAGE attenuated the LPS-induced expression of IL-6 and CCL2. These results strongly suggest that the elevated AGE, HMGB1, and LPS in pregnant women up-regulate the expression of IL-6 and CCL2 via the RAGE system, leading to systemic inflammation such as PE/HDP.博士（医学）・乙第1451号・令和2年3月16日© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Prevention of Reg I-induced β-cell apoptosis by IL-6/dexamethasone through activation of HGF gene regulation

AbstractReg (regenerating gene) product, Reg protein, is induced in pancreatic β-cells and acts as autocrine/paracrine growth factor for regeneration via the cell surface Reg receptor. However, high concentrations of Reg I protein induced β-cell apoptosis. In the present study, we found that hepatocyte growth factor (HGF) attenuated the β-cell apoptosis induced by the high concentrations of Reg I protein and that the combined stimulation of interleukin-6 (IL-6) and dexamethasone (Dx) induced the accumulation of HGF mRNA as well as Reg I mRNA in β-cells. The accumulation of the HGF mRNA was caused by the activation of the HGF promoter. Deletion analysis revealed that the region of −96 to −92 of the HGF gene was responsible for the promoter activation by IL-6+Dx. The promoters contain a consensus transcription factor binding sequence for signal transducer and activator of transcription (STAT). Site-directed mutations of STAT-binding motif in the region markedly attenuated the HGF promoter activity. Chromatin immunoprecipitation assay showed that STAT3 is located at the active HGF promoter in response to IL-6+Dx stimulation. These results strongly suggest that the combined stimulation of IL-6 and glucocorticoids induces the activation of both Reg and HGF genes and that the anti-apoptotic effects of HGF against the Reg I-induced apoptosis may help β-cell regeneration by Reg I protein

Secretion of Streptomyces mobaraensis pro-transglutaminase by coryneform bacteria

We previously reported on the secretion of Streptomyces mobaraensis transglutaminase by Corynebacterium glutamicum ATCC13869 (formerly classified as Brevibacterium lactofermentum). In the present work, we investigated whether any other coryneform bacteria showed higher productivity than C. glutamicum ATCC13869. We found that most coryneform species secreted pro-transglutaminase efficiently. Moreover, we confirmed that Corynebacterium ammoniagenes ATCC6872 produced about 2.5 g/l pro-transglutaminase over a 71-h period in a jar fermentor. Our findings suggest that some other coryneform bacteria, especially C. ammoniagenes ATCC6872, are potential hosts for industrial scale protein production

BioHackathon series in 2011 and 2012: penetration of ontology and linked data in life science domains

The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed