start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=5991 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210316 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9(-/-) and Gal-9(wt/wt) C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9(-/-) mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9(wt/wt) mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9(-/-) mice receiving Gal-9(-/-) or Gal-9(wt/wt) bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9(wt/wt) mice receiving Gal-9(-/-) BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H2O2. The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity. en-copyright= kn-copyright= en-aut-name=NunoueTomokazu en-aut-sei=Nunoue en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaguchiSatoshi en-aut-sei=Yamaguchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TeshigawaraSanae en-aut-sei=Teshigawara en-aut-mei=Sanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatayamaAkihiro en-aut-sei=Katayama en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakatsukaAtsuko en-aut-sei=Nakatsuka en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NikiToshiro en-aut-sei=Niki en-aut-mei=Toshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Immunology, Kagawa University kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=1 article-no= start-page=373 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210319 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Vaspin-HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Proximal tubular cells (PTCs) are crucial for maintaining renal homeostasis, and tubular injuries contribute to progression of diabetic kidney disease (DKD). However, the roles of visceral adipose tissue-derived serine protease inhibitor (vaspin) in the development of DKD is not known. We found vaspin maintains PTCs through ameliorating ER stress, autophagy impairment, and lysosome dysfunction in DKD. Vaspin-/- obese mice showed enlarged and leaky lysosomes in PTCs associated with increased apoptosis, and these abnormalities were also observed in the patients with DKD. During internalization into PTCs, vaspin formed a complex with heat shock protein family A (Hsp70) member 1 like (HSPA1L) as well as 78kDa glucose-regulated protein (GRP78). Both vaspin-partners bind to clathrin heavy chain and involve in the endocytosis. Notably, albumin-overload enhanced extracellular release of HSPA1L and overexpression of HSPA1L dissolved organelle stresses, especially autophagy impairment. Thus, vapsin/HSPA1L-mediated pathways play critical roles in maintaining organellar function of PTCs in DKD. en-copyright= kn-copyright= en-aut-name=NakatsukaAtsuko en-aut-sei=Nakatsuka en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaguchiSatoshi en-aut-sei=Yamaguchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakutaShigeru en-aut-sei=Kakuta en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwakuraYoichiro en-aut-sei=Iwakura en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, the University of Tokyo kn-affil= affil-num=5 en-affil=Research Institute for Biomedical Sciences, Tokyo University of Science kn-affil= affil-num=6 en-affil=Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=1100 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structure of photosystem I-LHCI-LHCII from the green alga Chlamydomonas reinhardtii in State 2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosystem I (PSI) and II (PSII) balance their light energy distribution absorbed by their light-harvesting complexes (LHCs) through state transition to maintain the maximum photosynthetic performance and to avoid photodamage. In state 2, a part of LHCII moves to PSI, forming a PSI-LHCI-LHCII supercomplex. The green alga Chlamydomonas reinhardtii exhibits state transition to a far larger extent than higher plants. Here we report the cryo-electron microscopy structure of a PSI-LHCI-LHCII supercomplex in state 2 from C. reinhardtii at 3.42?? resolution. The result reveals that the PSI-LHCI-LHCII of C. reinhardtii binds two LHCII trimers in addition to ten LHCI subunits. The PSI core subunits PsaO and PsaH, which were missed or not well-resolved in previous Cr-PSI-LHCI structures, are observed. The present results reveal the organization and assembly of PSI core subunits, LHCI and LHCII, pigment arrangement, and possible pathways of energy transfer from peripheral antennae to the PSI core. en-copyright= kn-copyright= en-aut-name=HuangZihui en-aut-sei=Huang en-aut-mei=Zihui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShenLiangliang en-aut-sei=Shen en-aut-mei=Liangliang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangWenda en-aut-sei=Wang en-aut-mei=Wenda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaoZhiyuan en-aut-sei=Mao en-aut-mei=Zhiyuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YiXiaohan en-aut-sei=Yi en-aut-mei=Xiaohan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuangTingyun en-aut-sei=Kuang en-aut-mei=Tingyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZhangXing en-aut-sei=Zhang en-aut-mei=Xing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HanGuangye en-aut-sei=Han en-aut-mei=Guangye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Biophysics, and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=2 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=5 en-affil=Department of Biophysics, and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=6 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=7 en-affil=Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Department of Biophysics, and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=9 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue= article-no= start-page=2 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gravity sensing in plant and animal cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gravity determines shape of body tissue and affects the functions of life, both in plants and animals. The cellular response to gravity is an active process of mechanotransduction. Although plants and animals share some common mechanisms of gravity sensing in spite of their distant phylogenetic origin, each species has its own mechanism to sense and respond to gravity. In this review, we discuss current understanding regarding the mechanisms of cellular gravity sensing in plants and animals. Understanding gravisensing also contributes to life on Earth, e.g., understanding osteoporosis and muscle atrophy. Furthermore, in the current age of Mars exploration, understanding cellular responses to gravity will form the foundation of living in space. en-copyright= kn-copyright= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiHideyuki en-aut-sei=Takahashi en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FuruichiTakuya en-aut-sei=Furuichi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ToyotaMasatsugu en-aut-sei=Toyota en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Furutani-SeikiMakoto en-aut-sei=Furutani-Seiki en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiTakeshi en-aut-sei=Kobayashi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Watanabe-TakanoHaruko en-aut-sei=Watanabe-Takano en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShinoharaMasahiro en-aut-sei=Shinohara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Numaga-TomitaTakuro en-aut-sei=Numaga-Tomita en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Sakaue-SawanoAsako en-aut-sei=Sakaue-Sawano en-aut-mei=Asako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MiyawakiAtsushi en-aut-sei=Miyawaki en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=3 en-affil=Faculty of Human Life Sciences, Hagoromo University of International Studies kn-affil= affil-num=4 en-affil=Department of Biochemistry and Molecular Biology, Saitama University kn-affil= affil-num=5 en-affil=Department of Systems Biochemistry in Regeneration and Pathology, Graduate School of Medicine, Yamaguchi University kn-affil= affil-num=6 en-affil=Department of Integrative Physiology, Graduate School of Medicine, Nagoya University kn-affil= affil-num=7 en-affil=Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute kn-affil= affil-num=8 en-affil=Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities kn-affil= affil-num=9 en-affil=Department of Molecular Pharmacology, Shinshu University School of Medicine kn-affil= affil-num=10 en-affil=Lab for Cell Function and Dynamics, CBS, RIKEN kn-affil= affil-num=11 en-affil=Lab for Cell Function and Dynamics, CBS, RIKEN kn-affil= affil-num=12 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=16490 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201005 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spred2-deficiency enhances the proliferation of lung epithelial cells and alleviates pulmonary fibrosis induced by bleomycin en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mitogen-activated protein kinase (MAPK) pathways are involved in many cellular processes, including the development of fibrosis. Here, we examined the role of Sprouty-related EVH-1-domain-containing protein (Spred) 2, a negative regulator of the MAPK-ERK pathway, in the development of bleomycin (BLM)-induced pulmonary fibrosis (PF). Compared to WT mice, Spred2?/? mice developed milder PF with increased proliferation of bronchial epithelial cells. Spred2?/? lung epithelial cells or MLE-12 cells treated with spred2 siRNA proliferated faster than control cells in vitro. Spred2?/? and WT macrophages produced similar levels of TNFƒ¿ and MCP-1 in response to BLM or lipopolysaccharide and myeloid cell-specific deletion of Spred2 in mice had no effect. Spred2?/? fibroblasts proliferated faster and produced similar levels of MCP-1 compared to WT fibroblasts. Spred2 mRNA was almost exclusively detected in bronchial epithelial cells of na?ve WT mice and it accumulated in approximately 50% of cells with a characteristic of Clara cells, 14 days after BLM treatment. These results suggest that Spred2 is involved in the regulation of tissue repair after BLM-induced lung injury and increased proliferation of lung bronchial cells in Spred2?/? mice may contribute to faster tissue repair. Thus, Spred2 may present a new therapeutic target for the treatment of PF. en-copyright= kn-copyright= en-aut-name=KawaraAkina en-aut-sei=Kawara en-aut-mei=Akina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MizutaRyo en-aut-sei=Mizuta en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItoToshihiro en-aut-sei=Ito en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiChunning en-aut-sei=Li en-aut-mei=Chunning kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraKaoru en-aut-sei=Nakamura en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SunCuiming en-aut-sei=Sun en-aut-mei=Cuiming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KuwabaraMasaki en-aut-sei=Kuwabara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KitabatakeMasahiro en-aut-sei=Kitabatake en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Immunology, Nara Medical University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=9 en-affil=Department of Immunology, Nara Medical University kn-affil= affil-num=10 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È affil-num=11 en-affil=Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= en-keyword=Cell signalling kn-keyword=Cell signalling en-keyword=Mechanisms of disease kn-keyword=Mechanisms of disease END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=14711 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200907 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mechanism underlying hippocampal long-term potentiation and depression based on competition between endocytosis and exocytosis of AMPA receptors en-subtitle= kn-subtitle= en-abstract= kn-abstract=N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) and long-term depression (LTD) of signal transmission form neural circuits and thus are thought to underlie learning and memory. These mechanisms are mediated by AMPA receptor (AMPAR) trafficking in postsynaptic neurons. However, the regulatory mechanism of bidirectional plasticity at excitatory synapses remains unclear. We present a network model of AMPAR trafficking for adult hippocampal pyramidal neurons, which reproduces both LTP and LTD. We show that the induction of both LTP and LTD is regulated by the competition between exocytosis and endocytosis of AMPARs, which are mediated by the calcium-sensors synaptotagmin 1/7 (Syt1/7) and protein interacting with C-kinase 1 (PICK1), respectively. Our result indicates that recycling endosomes containing AMPAR are always ready for Syt1/7-dependent exocytosis of AMPAR at peri-synaptic/synaptic membranes. This is because molecular motor myosin V-b constitutively transports the recycling endosome toward the membrane in a Ca2+-independent manner. en-copyright= kn-copyright= en-aut-name=SumiTomonari en-aut-sei=Sumi en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaradaKouji en-aut-sei=Harada en-aut-mei=Kouji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Computer Science and Engineering, Toyohashi University of Technology kn-affil= en-keyword=Biophysical models kn-keyword=Biophysical models en-keyword=Long-term depression kn-keyword=Long-term depression en-keyword=Long-term potentiation kn-keyword=Long-term potentiation END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=4387 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200309 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Three-dimensional observation and analysis of remineralization in dentinal caries lesions en-subtitle= kn-subtitle= en-abstract= kn-abstract=The remineralization mechanism in dental caries lesions is not completely understood. This study reports on ultrastructural and chemical changes observed within arrested caries lesions. Carious human teeth were observed using scanning electron microscopy (SEM) and focused-ion-beam (FIB)-SEM. The crystals detected in the caries lesions were characterized by transmission electron microscopy (TEM), along with chemical element mapping using energy-dispersive spectroscopy (EDS)-STEM. FIB-SEM 3D reconstructions revealed a severely damaged dentin surface abundantly covered by bacteria. Although the dentin tubules were clogged up to a depth of 100 mu m, bacterial invasion into dentin tubules was not observed. TEM crystal analysis and EDS-STEM revealed the presence of Ca and P, as well as of Mg within the HAp crystals deposited inside the dentin tubules. It was concluded that extensive remineralization with deposition of Mg-HAp crystals had occurred in dentin tubules of caries-arrested dentin. Understanding the natural remineralization process is thought to be helpful for developing clinical biomimetic remineralization protocols. en-copyright= kn-copyright= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraAkiko en-aut-sei=Nakamura en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaraToru en-aut-sei=Hara en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HayakawaSatoshi en-aut-sei=Hayakawa en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Van MeerbeekMeerbeek, Bart en-aut-sei=Van Meerbeek en-aut-mei=Meerbeek, Bart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Pathology & Experimental Medicine kn-affil= affil-num=2 en-affil=Okayama University Dental School, Advanced Research Center for Oral and Craniofacial Sciences kn-affil= affil-num=3 en-affil=National Institute for Materials Science kn-affil= affil-num=4 en-affil=National Institute for Materials Science kn-affil= affil-num=5 en-affil=Okayama University, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Biomaterials Laboratory kn-affil= affil-num=6 en-affil=Hokkaido University, Faculty of Dental Medicine, Department of Biomaterials and Bioengineering kn-affil= affil-num=7 en-affil=KU Leuven (University of Leuven), Department of Oral Health Research, BIOMAT & UZ Leuven (University Hospitals Leuven) kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=6486 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Whitish daytime radiative cooling using diffuse reflection of non-resonant silica nanoshells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Daytime radiative cooling offers efficient passive cooling of objects by tailoring their spectral responses, holding great promise for green photonics applications. A specular reflector has been utilized in cooling devices to minimize sunlight absorption, but such a glaring surface is visually less appealing, thus undesirable for public use. Here, by exploiting strong diffuse reflection of silica nanoshells in a polymer matrix, daytime radiative cooling below the ambient temperature is experimentally demonstrated, while showing whitish color under sunlight. The cooling device consists of a poly(methyl methacrylate) layer with randomly distributed silica nanoshells and a polydimethylsiloxane (PDMS) layer on an Ag mirror. The non-resonant nanoshells exhibit uniform diffuse reflection over the solar spectrum, while fully transparent for a selective thermal radiation from the underneath PDMS layer. In the temperature measurement under the sunlight irradiation, the device shows 2.3 degrees C cooler than the ambient, which is comparable to or even better than the conventional device without the nanoshells. Our approach provides a simple yet powerful nanophotonic structure for realizing a scalable and practical daytime radiative cooling device without a glaring reflective surface. en-copyright= kn-copyright= en-aut-name=SuichiTakahiro en-aut-sei=Suichi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaAtsushi en-aut-sei=Ishikawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaTakuo en-aut-sei=Tanaka en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HayashiYasuhiko en-aut-sei=Hayashi en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsurutaKenji en-aut-sei=Tsuruta en-aut-mei=Kenji kn-aut-name=Œ’“ñ kn-aut-sei= kn-aut-mei=Œ’“ñ aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Electrical and Electronic Engineering, Okayama University kn-affil= affil-num=2 en-affil=Department of Electrical and Electronic Engineering, Okayama University kn-affil= affil-num=3 en-affil=Metamaterials Laboratory, RIKEN Cluster for Pioneering Research kn-affil= affil-num=4 en-affil=Department of Electrical and Electronic Engineering, Okayama University kn-affil= affil-num=5 en-affil=Department of Electrical and Electronic Engineering, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=282 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transversus Abdominis Plane Block Reduced Early Postoperative Pain after Robot-assisted Prostatectomy: a Randomized Controlled Trial en-subtitle= kn-subtitle= en-abstract= kn-abstract=Analgesic effect of transversus abdominis plane block (TAP block) in lower major abdominal laparoscopic surgery with about 5 cm of maximum surgical scar has been controversial. We hypothesized that TAP block has benefits, so the analgesic effect of TAP block after robot-assisted laparoscopic prostatectomy (RALP) was evaluated. One hundred patients were enrolled in this prospective, double-blinded, randomized study. Standardized general anesthesia with wound infiltration on camera port and fentanyl dose limit of 3 mu g/kg was provided. Ultrasound-guided, single-shot subcostal TAP block with either 0.375% ropivacaine (Ropivacaine group, 48 patients) or normal saline (Control group, 52 patients) was performed by anesthesiologist in charge (34 anesthesiologists) after surgical procedure. Pain score using numerical rating scale (NRS) and postoperative intravenous fentanyl were evaluated for the first 24 postoperative hours. Median values (interquartile range) of NRS scores when the patients were transferred to post-anesthesia care unit (PACU) were 5 (2-7) in Ropivacaine group and 6 (4-8) in Control group at rest (P = 0.03), 5 (2-8) in Ropivacaine group and 7 (5-8) in Control group during movement (P < 0.01). These significant differences disappeared at the time of discharging PACU. Fentanyl doses for the first 24 postoperative hours were 210 mu g (120-360) in Ropivacaine group and 200 mu g (120-370) in Control group (P = 0.79). These results indicated that subcostal TAP block by anesthesiologists of varied level of training reduced postoperative pain immediate after RALP. TAP block had fundamental analgesic effect, but this benefit was too small to reduce postoperative 24-hour fentanyl consumption. en-copyright= kn-copyright= en-aut-name=TaninishiHideki en-aut-sei=Taninishi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsusakiTakashi en-aut-sei=Matsusaki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=282 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vectorial Proton Transport Mechanism of RxR, a Phylogenetically Distinct and Thermally Stable Microbial Rhodopsin en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rubrobacter xylanophilus rhodopsin (RxR) is a phylogenetically distinct and thermally stable seven-transmembrane protein that functions as a light-driven proton (H+) pump with the chromophore retinal. To characterize its vectorial proton transport mechanism, mutational and theoretical investigations were performed for carboxylates in the transmembrane region of RxR and the sequential proton transport steps were revealed as follows: (i) a proton of the retinylidene Schiff base (Lys209) is transferred to the counterion Asp74 upon formation of the blue-shifted M-intermediate in collaboration with Asp205, and simultaneously, a respective proton is released from the proton releasing group (Glu187/Glu197) to the extracellular side, (ii) a proton of Asp85 is transferred to the Schiff base during M-decay, (iii) a proton is taken up from the intracellular side to Asp85 during decay of the red-shifted O-intermediate. This ion transport mechanism of RxR provides valuable information to understand other ion transporters since carboxylates are generally essential for their functions. en-copyright= kn-copyright= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UetaTetsuya en-aut-sei=Ueta en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NojiTomoyasu en-aut-sei=Noji en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoKeisuke en-aut-sei=Saito en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KaneharaKanae en-aut-sei=Kanehara en-aut-mei=Kanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshizawaSusumu en-aut-sei=Yoshizawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshikitaHiroshi en-aut-sei=Ishikita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=5 en-affil=Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo kn-affil= affil-num=8 en-affil=Faculty of Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Biochemistry kn-keyword=Biochemistry en-keyword=Biophysics kn-keyword=Biophysics END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=3507 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200226 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Precise MEP monitoring with a reduced interval is safe and useful for detecting permissive duration for temporary clipping en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although temporary clipping of the parent artery is an indispensable technique in clipping surgery for intracranial aneurysms, the permissive duration of temporary clipping is still not well known. The aim of this study is to confirm the safety of precise motor evoked potential (MEP) monitoring and to estimate the permissive duration of temporary clipping for middle cerebral artery (MCA) aneurysm based on precise MEP monitoring results. Under precise MEP monitoring via direct cortical stimulation every 30 seconds to 1 minute, surgeons released a temporary clip and waited for MEP amplitude to recover following severe (>50%) reduction of MEP amplitude during temporary clipping. Precise MEP monitoring was safely performed. Twenty-eight instances of temporary clipping were performed in 42 MCA aneurysm clipping surgeries. Because precise MEP monitoring could be used to determine when to release a temporary clip even with a severe reduction in MEP amplitude due to lengthy temporary clipping, no patients experienced permanent postoperative hemiparesis. Based on logistic regression analysis, if a temporary clip is applied for 312 seconds or more, there is a higher probability of a severe reduction in MEP amplitude. We should therefore release temporary clips after 5 minutes in order to avoid permanent postoperative hemiparesis. en-copyright= kn-copyright= en-aut-name=KamedaMasahiro en-aut-sei=Kameda en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HishikawaTomohito en-aut-sei=Hishikawa en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiramatsuMasafumi en-aut-sei=Hiramatsu en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurozumiKazuhiko en-aut-sei=Kurozumi en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=epartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=epartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Stroke kn-keyword=Stroke END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=1578 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200131 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multi-drug therapy for epilepsy influenced bispectral index after a bolus propofol administration without affecting propofol's pharmacokinetics: a prospective cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Some previous studies have indicated that valproate (VPA) might change the pharmacokinetics and enhance the effects of propofol. We evaluated whether clinical VPA therapy affected the propofol blood level, the protein-unbound free propofol level, and/or the anesthetic effects of propofol in the clinical setting. The subjects were divided into the control group (not medicated with antiepileptics), the mono-VPA group (medicated with VPA alone), and the poly-VPA group (medicated with VPA, other antiepileptics, and/or psychoactive drugs). General anesthesia was induced via the administration of a single bolus of propofol and a remifentanil infusion, and when the bispectral index (BIS) exceeded 60 sevoflurane was started. There were no significant differences in the total blood propofol level at 5, 10, 15, and 20 min or the protein-unbound free propofol level at 5 min after the intravenous administration of propofol between the 3 groups. However, the minimum BIS was significantly lower and the time until the BIS exceeded 60 was significantly longer in the poly-VPA group. In the multivariate regression analysis, belonging to the poly-VPA group was found to be independently associated with the minimum BIS value and the time until the BIS exceeded 60. Clinical VPA therapy did not influence the pharmacokinetics of propofol. However, multi-drug therapy involving VPA might enhance the anesthetic effects of propofol. en-copyright= kn-copyright= en-aut-name=KodamaMatsuri en-aut-sei=Kodama en-aut-mei=Matsuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiguchiHitoshi en-aut-sei=Higuchi en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Ishii-MaruhamaMinako en-aut-sei=Ishii-Maruhama en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakanoMai en-aut-sei=Nakano en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Honda-WakasugiYuka en-aut-sei=Honda-Wakasugi en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaedaShigeru en-aut-sei=Maeda en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyawakiTakuya en-aut-sei=Miyawaki en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Drug regulation kn-keyword=Drug regulation en-keyword=Phase IV trials kn-keyword=Phase IV trials END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=4798 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200316 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of an experimental method of systematically estimating protein expression limits in HEK293 cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Protein overexpression sometimes causes cellular defects, although the underlying mechanism is still unknown. A protein's expression limit, which triggers cellular defects, is a useful indication of the underlying mechanism. In this study, we developed an experimental method of estimating the expression limits of target proteins in the human embryonic kidney cell line HEK293 by measuring the proteins' expression levels in cells that survived after the high-copy introduction of plasmid DNA by which the proteins were expressed under a strong cytomegalovirus promoter. The expression limits of nonfluorescent target proteins were indirectly estimated by measuring the levels of green fluorescent protein (GFP) connected to the target proteins with the self-cleaving sequence P2A. The expression limit of a model GFP was similar to 5.0% of the total protein, and sustained GFP overexpression caused cell death. The expression limits of GFPs with mitochondria-targeting signals and endoplasmic reticulum localization signals were 1.6% and 0.38%, respectively. The expression limits of four proteins involved in vesicular trafficking were far lower compared to a red fluorescent protein. The protein expression limit estimation method developed will be valuable for defining toxic proteins and consequences of protein overexpression. en-copyright= kn-copyright= en-aut-name=MoriYoshihiro en-aut-sei=Mori en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaYuki en-aut-sei=Yoshida en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriyaHisao en-aut-sei=Moriya en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Sony Computer Science Laboratories kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Research Core for Interdisciplinary Sciences, Okayama University kn-affil= en-keyword=Biological techniques kn-keyword=Biological techniques en-keyword=Cell biology kn-keyword=Cell biology en-keyword=Gene expression analysis kn-keyword=Gene expression analysis en-keyword=Molecular biology kn-keyword=Molecular biology en-keyword=Protein translocation kn-keyword=Protein translocation en-keyword=Protein transport kn-keyword=Protein transport END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=9500 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200611 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=N-terminal deletion of Swi3 created by the deletion of a dubious ORF YJL175W mitigates protein burden effect in S. cerevisiae en-subtitle= kn-subtitle= en-abstract= kn-abstract=Extreme overproduction of gratuitous proteins can overload cellular protein production resources, leading to growth defects, a phenomenon known as the protein burden/cost effect. Genetic screening in the budding yeast Saccharomyces cerevisiae has isolated several dubious ORFs whose deletions mitigated the protein burden effect, but individual characterization thereof has yet to be delineated. We found that deletion of the YJL175W ORF yielded an N-terminal deletion of Swi3, a subunit of the SWI/SNF chromatin remodeling complex, and partial loss of function of Swi3. The deletion mutant showed a reduction in transcription of genes encoding highly expressed, secreted proteins and an overall reduction in translation. Mutations in the chromatin remodeling complex could thus mitigate the protein burden effect, likely by reallocating residual cellular resources used to overproduce proteins. This cellular state might also be related to cancer cells, as they frequently harbor mutations in the SWI/SNF complex. en-copyright= kn-copyright= en-aut-name=SaekiNozomu en-aut-sei=Saeki en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EguchiYuichi en-aut-sei=Eguchi en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KintakaReiko en-aut-sei=Kintaka en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MakanaeKoji en-aut-sei=Makanae en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShichinoYuichi en-aut-sei=Shichino en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwasakiShintaro en-aut-sei=Iwasaki en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KannoManabu en-aut-sei=Kanno en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KimuraNobutada en-aut-sei=Kimura en-aut-mei=Nobutada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriyaHisao en-aut-sei=Moriya en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Center for Mechanisms of Evolution, School of Life Sciences, Arizona State University kn-affil= affil-num=3 en-affil=Donnelly Center for Cellular and Biomolecular Research, Department of Medical Genetics, University of Toronto kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research kn-affil= affil-num=6 en-affil=RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research kn-affil= affil-num=7 en-affil=Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=8 en-affil=Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=9 en-affil=Research Core for Interdisciplinary Sciences, Okayama University kn-affil= en-keyword=Cell growth kn-keyword=Cell growth en-keyword=Gene expression kn-keyword=Gene expression en-keyword=Gene regulation kn-keyword=Gene regulation END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=6869 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200422 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Deficiency of CD44 prevents thoracic aortic dissection in a murine model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thoracic aortic dissection (TAD) is a life-threatening vascular disease. We showed that CD44, a widely distributed cell surface adhesion molecule, has an important role in inflammation. In this study, we examined the role of CD44 in the development of TAD. TAD was induced by the continuous infusion of beta-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, and angiotensin II (AngII) for 7 days in wild type (WT) mice and CD44 deficient (CD44(-/-)) mice. The incidence of TAD in CD44(-/-) mice was significantly reduced compared with WT mice (44% and 6%, p<0.01). Next, to evaluate the initial changes, aortic tissues at 24hours after BAPN/AngII infusion were examined. Neutrophil accumulation into thoracic aortic adventitia in CD44(-/-) mice was significantly decreased compared with that in WT mice (5.7 +/- 0.3% and 1.6 +/- 0.4%, p<0.01). In addition, BAPN/AngII induced interleukin-6, interleukin-1 beta, matrix metalloproteinase-2 and matrix metalloproteinase-9 in WT mice, all of which were significantly reduced in CD44(-/-) mice (all p<0.01). In vitro transmigration of neutrophils from CD44(-/-) mice through an endothelial monolayer was significantly decreased by 18% compared with WT mice (p<0.01). Our findings indicate that CD44 has a critical role in TAD development in association with neutrophil infiltration into adventitia. en-copyright= kn-copyright= en-aut-name=HatipogluOmer F. en-aut-sei=Hatipoglu en-aut-mei=Omer F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YonezawaTomoko en-aut-sei=Yonezawa en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoMegumi en-aut-sei=Kondo en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AmiokaNaofumi en-aut-sei=Amioka en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=9 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= en-keyword=Aneurysm kn-keyword=Aneurysm en-keyword=Aortic diseases kn-keyword=Aortic diseases END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=7307 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Controlling Electronic States of Few-walled Carbon Nanotube Yarn via Joule-annealing and p-type Doping Towards Large Thermoelectric Power Factor en-subtitle= kn-subtitle= en-abstract= kn-abstract=Flexible, light-weight and robust thermoelectric (TE) materials have attracted much attention to convert waste heat from low-grade heat sources, such as human body, to electricity. Carbon nanotube (CNT) yarn is one of the potential TE materials owing to its narrow band-gap energy, high charge carrier mobility, and excellent mechanical property, which is conducive for flexible and wearable devices. Herein, we propose a way to improve the power factor of CNT yarns fabricated from few-walled carbon nanotubes (FWCNTs) by two-step method; Joule-annealing in the vacuum followed by doping with p-type dopants, 2,3,5,6-tetrafluo-7,7,8,8-tetracyanoquinodimethane (F4TCNQ). Numerical calculations and experimental results explain that Joule-annealing and doping modulate the electronic states (Fermi energy level) of FWCNTs, resulting in extremely large thermoelectric power factor of 2250 mu Wm(-1) K-2 at a measurement temperature of 423K. Joule-annealing removes amorphous carbon on the surface of the CNT yarn, which facilitates doping in the subsequent step, and leads to higher Seebeck coefficient due to the transformation from (semi) metallic to semiconductor behavior. Doping also significantly increases the electrical conductivity due to the effective charge transfers between CNT yarn and F4TCNQ upon the removal of amorphous carbon after Joule-annealing. en-copyright= kn-copyright= en-aut-name=MyintMay Thu Zar en-aut-sei=Myint en-aut-mei=May Thu Zar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishikawaTakeshi en-aut-sei=Nishikawa en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmotoKazuki en-aut-sei=Omoto en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueHirotaka en-aut-sei=Inoue en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamashitaYoshifumi en-aut-sei=Yamashita en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KyawAung Ko Ko en-aut-sei=Kyaw en-aut-mei=Aung Ko Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HayashiYasuhiko en-aut-sei=Hayashi en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Department of Electrical and Electronic Engineering, Southern University of Science and Technology kn-affil= affil-num=7 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Materials science kn-keyword=Materials science en-keyword=Nanoscience and technology kn-keyword=Nanoscience and technology END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=9414 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment. en-copyright= kn-copyright= en-aut-name=MoritaTakuya en-aut-sei=Morita en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KiyonoMasahiro en-aut-sei=Kiyono en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YokooSuguru en-aut-sei=Yokoo en-aut-mei=Suguru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Sarcoma kn-keyword=Sarcoma en-keyword=Translational research kn-keyword=Translational research END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=12581 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing en-subtitle= kn-subtitle= en-abstract= kn-abstract=The use of primary patient-derived organoids for drug sensitivity and resistance testing could play an important role in precision cancer medicine. We developed expandable ovarian cancer organoids in<3 weeks; these organoids captured the characteristics of histological cancer subtypes and replicated the mutational landscape of the primary tumours. Seven pairs of organoids (3 high-grade serous, 1 clear cell, 3 endometrioid) and original tumours shared 59.5% (36.1-73.1%) of the variants identified. Copy number variations were also similar among organoids and primary tumours. The organoid that harboured the BRCA1 pathogenic variant (p.L63*) showed a higher sensitivity to PARP inhibitor, olaparib, as well as to platinum drugs compared to the other organoids, whereas an organoid derived from clear cell ovarian cancer was resistant to conventional drugs for ovarian cancer, namely platinum drugs, paclitaxel, and olaparib. The overall success rate of primary organoid culture, including those of various histological subtypes, was 80% (28/35). Our data show that patient-derived organoids are suitable physiological ex vivo cancer models that can be used to screen effective personalised ovarian cancer drugs. en-copyright= kn-copyright= en-aut-name=NankiYoshiko en-aut-sei=Nanki en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChiyodaTatsuyuki en-aut-sei=Chiyoda en-aut-mei=Tatsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OokuboAki en-aut-sei=Ookubo en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItohManabu en-aut-sei=Itoh en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UenoMasaru en-aut-sei=Ueno en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkahaneTomoko en-aut-sei=Akahane en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KameyamaKaori en-aut-sei=Kameyama en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamagamiWataru en-aut-sei=Yamagami en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KataokaFumio en-aut-sei=Kataoka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AokiDaisuke en-aut-sei=Aoki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=JSR?Keio University Medical and Chemical Innovation Center (JKiC), JSR Corp. kn-affil= affil-num=5 en-affil=JSR?Keio University Medical and Chemical Innovation Center (JKiC), JSR Corp. kn-affil= affil-num=6 en-affil=JSR?Keio University Medical and Chemical Innovation Center (JKiC), JSR Corp. kn-affil= affil-num=7 en-affil=JSR?Keio University Medical and Chemical Innovation Center (JKiC), Keio University School of Medicine kn-affil= affil-num=8 en-affil=Department of Pathology, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=10 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= affil-num=11 en-affil=Department of Obstetrics and Gynecology, Keio University School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=10876 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200702 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The role of RND-type efflux pumps in multidrug-resistant mutants of Klebsiella pneumoniae en-subtitle= kn-subtitle= en-abstract= kn-abstract=The emergence of multidrug-resistant Klebsiella pneumoniae is a worldwide problem. K. pneumoniae possesses numerous resistant genes in its genome. We isolated mutants resistant to various antimicrobials in vitro and investigated the importance of intrinsic genes in acquired resistance. The isolation frequency of the mutants was 10(-7)-10(-9). Of the multidrug-resistant mutants, hyper-multidrug-resistant mutants (EB256-1, EB256-2, Nov1-8, Nov2-2, and OX128) were identified, and accelerated efflux activity of ethidium from the inside to the outside of the cells was observed in these mutants. Therefore, we hypothesized that the multidrug efflux pump, especially RND-type efflux pump, would be related to changes of the phenotype. We cloned all RND-type multidrug efflux pumps from the K. pneumoniae genome and characterized them. KexEF and KexC were powerful multidrug efflux pumps, in addition to AcrAB, KexD, OqxAB, and EefABC, which were reported previously. It was revealed that the expression of eefA was increased in EB256-1 and EB256-2: the expression of oqxA was increased in OX128; the expression of kexF was increased in Nov2-2. It was found that a region of 1,485 bp upstream of kexF, was deleted in the genome of Nov2-2. K. pneumoniae possesses more potent RND-multidrug efflux systems than E. coli. However, we revealed that most of them did not contribute to the drug resistance of our strain at basic levels of expression. On the other hand, it was also noted that the overexpression of these pumps could lead to multidrug resistance based on exposure to antimicrobial chemicals. We conclude that these pumps may have a role to maintain the intrinsic resistance of K. pneumoniae when they are overexpressed. The antimicrobial chemicals selected many resistant mutants at the same minimum inhibitory concentration (MIC) or a concentration slightly higher than the MIC. These results support the importance of using antibiotics at appropriate concentrations at clinical sites. en-copyright= kn-copyright= en-aut-name=NiRui Ting en-aut-sei=Ni en-aut-mei=Rui Ting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnishiMotoyasu en-aut-sei=Onishi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MizusawaMinako en-aut-sei=Mizusawa en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitagawaRyoko en-aut-sei=Kitagawa en-aut-mei=Ryoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KishinoTakanori en-aut-sei=Kishino en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsubaraFutoshi en-aut-sei=Matsubara en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsuchiyaTomofusa en-aut-sei=Tsuchiya en-aut-mei=Tomofusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KurodaTeruo en-aut-sei=Kuroda en-aut-mei=Teruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OgawaWakano en-aut-sei=Ogawa en-aut-mei=Wakano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Microbiology, Faculty of Pharmaceutical Sciences,Okayama University kn-affil= affil-num=5 en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Microbiology and Biochemistry, Daiichi University of Pharmacy kn-affil= affil-num=7 en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Antimicrobial resistance kn-keyword=Antimicrobial resistance en-keyword=Bacteria kn-keyword=Bacteria en-keyword=Bacteriology kn-keyword=Bacteriology END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=10595 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200629 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lung perfusion scintigraphy to detect chronic lung allograft dysfunction after living-donor lobar lung transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Because chronic lung allograft dysfunction (CLAD) develops predominantly on one side after bilateral living-donor lobar lung transplantation (LDLLT), lung perfusion scintigraphy (Q-scinti) was expected to show a perfusion shift to the contralateral unaffected lung with the development of CLAD. Our study examined the potential usefulness of Q-scinti in the diagnosis of CLAD after bilateral LDLLT. We conducted a single-center retrospective cohort study of 58 recipients of bilateral LDLLT. The unilateral shift values on Q-scinti were calculated and compared between the CLAD group (N=27) and the non-CLAD group (N=31) from 5 years before to 5 years after the diagnosis of CLAD. The unilateral shift values in Q-scinti were significantly higher in the CLAD group than in the non-CLAD group from 5 years before the diagnosis of CLAD to 5 years after the diagnosis (P<0.05). The unilateral shift values in Q-scinti were significantly correlated with the percent baseline values of the forced expiratory volume in 1 s (P=0.0037), the total lung capacity (P=0.0028), and the forced vital capacity (P=0.00024) at the diagnosis of CLAD. In patients developing unilateral CLAD after bilateral LDLLT, Q-scinti showed a unilateral perfusion shift to the contralateral unaffected lung. Thus, Q-scinti appears to have the potential to predict unilateral CLAD after bilateral LDLLT. en-copyright= kn-copyright= en-aut-name=YamamotoHaruchika en-aut-sei=Yamamoto en-aut-mei=Haruchika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurosakiTakeshi en-aut-sei=Kurosaki en-aut-mei=Takeshi kn-aut-name= ‹BŽj kn-aut-sei= kn-aut-mei= ‹BŽj aut-affil-num=3 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtaniShinji en-aut-sei=Otani en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamaneMasaomi en-aut-sei=Yamane en-aut-mei=Masaomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtoTakahiro en-aut-sei=Oto en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Organ Transplant Center, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=10702 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Skewed electronic band structure induced by electric polarization in ferroelectric BaTiO3 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Skewed band structures have been empirically described in ferroelectric materials to explain the functioning of recently developed ferroelectric tunneling junction (FTJs). Nonvolatile ferroelectric random access memory (FeRAM) and the artificial neural network device based on the FTJ system are rapidly developing. However, because the actual ferroelectric band structure has not been elucidated, precise designing of devices has to be advanced through appropriate heuristics. Here, we perform angle-resolved hard X-ray photoemission spectroscopy of ferroelectric BaTiO3 thin films for the direct observation of ferroelectric band skewing structure as the depth profiles of atomic orbitals. The depth-resolved electronic band structure consists of three depth regions: a potential slope along the electric polarization in the core, the surface and interface exhibiting slight changes. We also demonstrate that the direction of the energy shift is controlled by the polarization reversal. In the ferroelectric skewed band structure, we found that the difference in energy shifts of the atomic orbitals is correlated with the atomic configuration of the soft phonon mode reflecting the Born effective charges. These findings lead to a better understanding of the origin of electric polarization. en-copyright= kn-copyright= en-aut-name=OshimeNorihiro en-aut-sei=Oshime en-aut-mei=Norihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanoJun en-aut-sei=Kano en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkenagaEiji en-aut-sei=Ikenaga en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasuiShintaro en-aut-sei=Yasui en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamasakiYosuke en-aut-sei=Hamasaki en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YasuharaSou en-aut-sei=Yasuhara en-aut-mei=Sou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HinokumaSatoshi en-aut-sei=Hinokuma en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IkedaNaoshi en-aut-sei=Ikeda en-aut-mei=Naoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=JanolinPierre-Eymeric en-aut-sei=Janolin en-aut-mei=Pierre-Eymeric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KiatJean-Michel en-aut-sei=Kiat en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ItohMitsuru en-aut-sei=Itoh en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YokoyaTakayoshi en-aut-sei=Yokoya en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiiTatsuo en-aut-sei=Fujii en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YasuiAkira en-aut-sei=Yasui en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OsawaHitoshi en-aut-sei=Osawa en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Japan Synchrotron Radiation Research Institute, JASRI kn-affil= affil-num=4 en-affil=Laboratory for Materials and Structures, Tokyo Institute of Technology kn-affil= affil-num=5 en-affil=Laboratory for Materials and Structures, Tokyo Institute of Technology kn-affil= affil-num=6 en-affil=Laboratory for Materials and Structures, Tokyo Institute of Technology kn-affil= affil-num=7 en-affil=Innovative Oxidation Team, Interdisciplinary Research Center for Catalytic Chemistry, National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=8 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Universit? Paris-Saclay,CentraleSup?lec, CNRS, Laboratoire SPMS kn-affil= affil-num=10 en-affil=Universit? Paris-Saclay,CentraleSup?lec, CNRS, Laboratoire SPMS kn-affil= affil-num=11 en-affil=Laboratory for Materials and Structures, Tokyo Institute of Technology kn-affil= affil-num=12 en-affil=GResearch Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=13 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=14 en-affil=Japan Synchrotron Radiation Research Institute, JASRI kn-affil= affil-num=15 en-affil=Japan Synchrotron Radiation Research Institute, JASRI kn-affil= END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=10418 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200626 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Decreased miR-200b-3p in cancer cells leads to angiogenesis in HCC by enhancing endothelial ERG expression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Transcription factor ERG (erythroblast transformation-specific (ETS)-related gene) is essential in endothelial differentiation and angiogenesis, in which microRNA (miR)-200b-3p targeting site is expected by miRNA target prediction database. miR-200b is known decreased in hepatocellular carcinoma (HCC), however, the functional relation between ERG and miR-200b-3p, originating from pre-miR-200b, in HCC angiogenesis remains unclear. We investigated whether hepatocyte-derived miR-200b-3p governs angiogenesis in HCC by targeting endothelial ERG. Levels of miR-200b-3p in HCC tissues were significantly lower than those in adjacent non-HCC tissues. Poorly differentiated HCC cell line expressed lower level of miR-200b-3p compared to well-differentiated HCC cell lines. The numbers of ERG-positive endothelial cells were higher in HCC tissues than in adjacent non-HCC tissues. There was a negative correlation between the number of ERG-positive cells and miR-200b-3p expression in HCC tissues. Culture supernatants of HCC cell lines with miR-200b-3p-overexpression reduced cell migration, proliferation and tube forming capacity in endothelial cells relative to the control, while those with miR-200b-3p-inhibition augmented the responses. Exosomes isolated from HCC culture supernatants with miR-200b-3p overexpression suppressed endothelial ERG expression. These results suggest that exosomal miR-200b-3p from hepatocytes suppresses endothelial ERG expression, and decreased miR-200b-3p in cancer cells promotes angiogenesis in HCC tissues by enhancing endothelial ERG expression. en-copyright= kn-copyright= en-aut-name=Moh-Moh-AungAye en-aut-sei=Moh-Moh-Aung en-aut-mei=Aye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItoSachio en-aut-sei=Ito en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatayamaHiroshi en-aut-sei=Katayama en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtaYoko en-aut-sei=Ota en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Molecular medicine kn-keyword=Molecular medicine en-keyword=Tumour angiogenesis kn-keyword=Tumour angiogenesis END