Academic PressActa Medica Okayama002186935562020Constructing indecomposable integrally closed modules over a two-dimensional regular local ring879907ENFutoshiHayasakaDepartment of Environmental and Mathematical Sciences, Okayama UniversityIn this article, we construct integrally closed modules of rank two over a two-dimensional regular local ring. The modules are explicitly constructed from a given complete monomial ideal with respect to a regular system of parameters. Then we investigate their indecomposability. As a consequence, we have a large class of indecomposable integrally closed modules whose Fitting ideal is not simple. This gives an answer to Kodiyalam's question.No potential conflict of interest relevant to this article was reported.Academic PressActa Medica Okayama0006291X52032019Development of a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells600605ENHengWeiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChenWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRuiGuoDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIschemic heart disease remains the largest cause of death worldwide. Accordingly, many researchers have sought curative options, often using laboratory animal models such as rodents. However, the physiology of the human heart differs significantly from that of the rodent heart. In this study, we developed a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells (hiPS-CMs). After optimizing the conditions of ischemia, including the concentration of oxygen and duration of application, we evaluated the consequent damage to hiPS-CMs. Notably, exposure to 2% oxygen, 0 mg/ml glucose, and 0% fetal bovine serum increased the percentage of nuclei stained with propidium iodide, an indicator of membrane damage, and decreased cellular viability. These conditions also decreased the contractility of hiPS-CMs. Furthermore, ischemic conditioning increased the mRNA expression of IL-8, consistent with observed conditions in the in vivo heart. Taken together, these findings suggest that our hiPS-CM-based model can provide a useful platform for human ischemic heart disease research.No potential conflict of interest relevant to this article was reported.Academic PressActa Medica Okayama004268225332019Two novel fungal negative-strand RNA viruses related to mymonaviruses and phenuiviruses in the shiitake mushroom (Lentinula edodes)125136EN Yu-HsinLinInstitute of Plant Science and Resources (IPSR), Okayama University MikiFujitaInstitute of Plant Science and Resources (IPSR), Okayama University SotaroChibaGraduate School of Bioagricultural Sciences, Nagoya University KiwamuHyodoInstitute of Plant Science and Resources (IPSR), Okayama University Ida BagusAndikaInstitute of Plant Science and Resources (IPSR), Okayama University NobuhiroSuzukiInstitute of Plant Science and Resources (IPSR), Okayama University HidekiKondoInstitute of Plant Science and Resources (IPSR), Okayama UniversityAbstract There is still limited information on the diversity of (−)ssRNA viruses that infect fungi. Here, we have discovered two novel (−)ssRNA mycoviruses in the shiitake mushroom (Lentinula edodes). The first virus has a monopartite RNA genome and relates to that of mymonaviruses (Mononegavirales), especially to Hubei rhabdo-like virus 4 from arthropods and thus designated as Lentinula edodes negative-strand RNA virus 1. The second virus has a putative bipartite RNA genome and is related to the recently discovered bipartite or tripartite phenui-like viruses (Bunyavirales) associated with plants and ticks, and designated as Lentinula edodes negative-strand RNA virus 2 (LeNSRV2). LeNSRV2 is likely the first segmented (−)ssRNA virus known to infect fungi. Its smaller RNA segment encodes a putative nucleocapsid and a plant MP-like protein using a potential ambisense coding strategy. These findings enhance our understanding of the diversity, evolution and spread of (−)ssRNA viruses in fungi.No potential conflict of interest relevant to this article was reported.Academic PressActa Medica Okayama0022039626052016Convex compact sets in RN-1 give traveling fronts of cooperation-diffusion systems in R-N43014338ENMasaharuTaniguchiThis paper studies traveling fronts to cooperation diffusion systems in R-N for N >= 3. We consider (N - 2)-dimensional smooth surfaces as boundaries of strictly convex compact sets in RN-1, and define an equivalence relation between them. We prove that there exists a traveling front associated with a given surface and show its stability. The associated traveling fronts coincide up to phase transition if and only if the given surfaces satisfy the equivalence relation. No potential conflict of interest relevant to this article was reported.Academic PressActa Medica Okayama09699961502013CACNA1A variants may modify the epileptic phenotype of Dravet syndrome209217ENIoriOhmoriDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMamoruOuchidaDepartment of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKatsuhiroKobayashiYoshimiJitsumoriAkikoMoriDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyukiMichiueDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTeiichiNishikiDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYokoOhtsukaHidekiMatsuiDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Dravet syndrome is an intractable epileptic syndrome beginning in the first year of life. De novo mutations of SCN1A, which encode the Na(v)1.1 neuronal voltage-gated sodium channel, are considered the major cause of Dravet syndrome. In this study, we investigated genetic modifiers of this syndrome. We performed a mutational analysis of all coding exons of CACNA1A in 48 subjects with Dravet syndrome. To assess the effects of CACNA1A variants on the epileptic phenotypes of Dravet syndrome, we compared clinical features in two genotype groups: 1) subjects harboring SCN1A mutations but no CACNA1A variants (n=20) and 2) subjects with SCN1A mutations plus CACNA1A variants (n=20). CACNA1A variants detected in patients were studied using heterologous expression of recombinant human Ca(v)2.1 in HEK 293 cells and whole-cell patch-clamp recording. Nine CACNA1A variants, including six novel ones, were detected in 21 of the 48 subjects (43.8%). Based on the incidence of variants in healthy controls, most of the variants seemed to be common polymorphisms. However, the subjects harboring SCN1A mutations and CACNA1A variants had absence seizures more frequently than the patients with only SCN1A mutations (8/20 vs. 0/20, p=0.002). Moreover, the former group of subjects exhibited earlier onset of seizures and more frequent prolonged seizures before one year of age, compared to the latter group of subjects. The electrophysiological properties of four of the five novel Ca(v)2.1 variants exhibited biophysical changes consistent with gain-of-function. We conclude that CACNA1A variants in some persons with Dravet syndrome may modify the epileptic phenotypes.No potential conflict of interest relevant to this article was reported.Academic PressActa Medica Okayama0006-291X36612008Inhibition of tumor-stromal interaction through HGF/Met signaling by valproic acid110116ENYohsukeMatsumotoTakahiroMotokiSatoshiKubotaMasaharuTakigawaHirohitoTsubouchiEiichiGohdaHepatocyte growth factor (HGF), which is produced by surrounding stromal cells, including fibroblasts and endothelial cells, has been shown to be a significant factor responsible for cancer cell invasion mediated by tumor-stromal interactions. We found in this study that the anti-tumor agent valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, strongly inhibited tumor-stromal interaction. VPA inhibited HGF production in fibroblasts induced by epidermal growth factor (EGF), platelet-derived growth factor, basic fibroblast growth factor, phorbol 12-myristate 13-acetate (PMA) and prostaglandin E-2 without any appreciable cytotoxic effect. Other HDAC inhibitors, including butyric acid and trichostatin A (TSA), showed similar inhibitory effects on HGF production stimulated by various inducers. Up-regulations of HGF gene expression induced by PMA and EGF were also suppressed by VPA and TSA. Furthermore, VPA significantly inhibited HGF-induced invasion of HepG2 hepatocellular carcinoma cells. VPA, however, did not affect the increases in phosphorylation of MAPK and Akt in HGF-treated HepG2 cells. These results demonstrated that VPA inhibited two critical processes of tumor-stromal interaction, induction of fibroblastic HGF production and HGF-induced invasion of HepG2 cells, and suggest that those activities serve for other anti-tumor mechanisms of VPA besides causing proliferation arrest, differentiation, and/or apoptosis of tumor cells.No potential conflict of interest relevant to this article was reported.