start-ver=1.4 cd-journal=joma no-vol=366 cd-vols= no-issue=1 article-no= start-page=110 end-page=116 dt-received= dt-revised= dt-accepted= dt-pub-year=2008 dt-pub=20080201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inhibition of tumor-stromal interaction through HGF/Met signaling by valproic acid en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hepatocyte 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. en-copyright= kn-copyright= en-aut-name=MatsumotoYohsuke en-aut-sei=Matsumoto en-aut-mei=Yohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MotokiTakahiro en-aut-sei=Motoki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakigawaMasaharu en-aut-sei=Takigawa en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsubouchiHirohito en-aut-sei=Tsubouchi en-aut-mei=Hirohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GohdaEiichi en-aut-sei=Gohda en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Department of Immunochemistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Immunochemistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Biochemistry and Molecular Dentistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Biochemistry and Molecular Dentistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Digestive Disease and Life-style Related Disease, Health Research Human and Environmental Sciences, Kagoshima University, Graduate School of Medicine and Dental Sciences affil-num=6 en-affil= kn-affil=Department of Immunochemistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=hepatocyte growth factor kn-keyword=hepatocyte growth factor en-keyword=valproic acid kn-keyword=valproic acid en-keyword=histone deacetylase inhibitor kn-keyword=histone deacetylase inhibitor en-keyword=butyric acid kn-keyword=butyric acid en-keyword=trichostatin A kn-keyword=trichostatin A en-keyword=induction kn-keyword=induction en-keyword=tumor invasion kn-keyword=tumor invasion en-keyword=dermal fibroblast kn-keyword=dermal fibroblast END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue= article-no= start-page=209 end-page=217 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=201302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CACNA1A variants may modify the epileptic phenotype of Dravet syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract= 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. en-copyright= kn-copyright= en-aut-name=OhmoriIori en-aut-sei=Ohmori en-aut-mei=Iori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=JitsumoriYoshimi en-aut-sei=Jitsumori en-aut-mei=Yoshimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriAkiko en-aut-sei=Mori en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishikiTeiichi en-aut-sei=Nishiki en-aut-mei=Teiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhtsukaYoko en-aut-sei=Ohtsuka en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuiHideki en-aut-sei=Matsui en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil= kn-affil= affil-num=5 en-affil=Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil= kn-affil= affil-num=9 en-affil=Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=260 cd-vols= no-issue=5 article-no= start-page=4301 end-page=4338 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Convex compact sets in RN-1 give traveling fronts of cooperation-diffusion systems in R-N en-subtitle= kn-subtitle= en-abstract= kn-abstract=This 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. en-copyright= kn-copyright= en-aut-name=TaniguchiMasaharu en-aut-sei=Taniguchi en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Department of Mathematics, Faculty of Science, Okayama University en-keyword=Traveling front kn-keyword=Traveling front en-keyword=Cooperation diffusion system kn-keyword=Cooperation diffusion system en-keyword=Non-symmetric kn-keyword=Non-symmetric END start-ver=1.4 cd-journal=joma no-vol=533 cd-vols= no-issue= article-no= start-page=125 end-page=136 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Two novel fungal negative-strand RNA viruses related to mymonaviruses and phenuiviruses in the shiitake mushroom (Lentinula edodes) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Abstract 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. en-copyright= kn-copyright= en-aut-name=Lin Yu-Hsin en-aut-sei=Lin en-aut-mei= Yu-Hsin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Fujita Miki en-aut-sei=Fujita en-aut-mei= Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Chiba Sotaro en-aut-sei=Chiba en-aut-mei= Sotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Hyodo Kiwamu en-aut-sei=Hyodo en-aut-mei= Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Andika Ida Bagus en-aut-sei=Andika en-aut-mei= Ida Bagus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Suzuki Nobuhiro en-aut-sei=Suzuki en-aut-mei= Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Kondo Hideki en-aut-sei=Kondo en-aut-mei= Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Bioagricultural Sciences, Nagoya University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=Ambisense kn-keyword=Ambisense en-keyword=Bipartite genome kn-keyword=Bipartite genome en-keyword=Endogenous virus element kn-keyword=Endogenous virus element en-keyword=Evolution kn-keyword=Evolution en-keyword=High-throughput sequencing kn-keyword=High-throughput sequencing en-keyword=Lentinula edodes kn-keyword=Lentinula edodes en-keyword=Mymonaviridae kn-keyword=Mymonaviridae en-keyword=Negative-strand RNA virus kn-keyword=Negative-strand RNA virus en-keyword=Phenuiviridae kn-keyword=Phenuiviridae en-keyword=Shitake mushroom kn-keyword=Shitake mushroom END start-ver=1.4 cd-journal=joma no-vol=520 cd-vols= no-issue=3 article-no= start-page=600 end-page=605 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ischemic 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. en-copyright= kn-copyright= en-aut-name=WeiHeng en-aut-sei=Wei en-aut-mei=Heng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangChen en-aut-sei=Wang en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GuoRui en-aut-sei=Guo en-aut-mei=Rui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cardiomyocytes kn-keyword=Cardiomyocytes en-keyword=Human induced pluripotent stem cells kn-keyword=Human induced pluripotent stem cells en-keyword=Ischemic heart disease kn-keyword=Ischemic heart disease en-keyword=Myocardial infarction kn-keyword=Myocardial infarction END start-ver=1.4 cd-journal=joma no-vol=556 cd-vols= no-issue= article-no= start-page=879 end-page=907 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200815 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Constructing indecomposable integrally closed modules over a two-dimensional regular local ring en-subtitle= kn-subtitle= en-abstract= kn-abstract=In 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. en-copyright= kn-copyright= en-aut-name=HayasakaFutoshi en-aut-sei=Hayasaka en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Environmental and Mathematical Sciences, Okayama University kn-affil= en-keyword=Integral closure kn-keyword=Integral closure en-keyword=Indecomposable module kn-keyword=Indecomposable module en-keyword=Monomial ideal kn-keyword=Monomial ideal en-keyword=Regular local ring kn-keyword=Regular local ring END