start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=8786 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficient and stable n-type sulfide overall water splitting with separated hydrogen production en-subtitle= kn-subtitle= en-abstract= kn-abstract=N-type sulfide semiconductors are promising photocatalysts due to their broad visible-light absorption, facile synthesis and chemical diversity. However, photocorrosion and limited electron transport in one-step excitation and solid-state Z-scheme systems hinder efficient overall water splitting. Liquid-phase Z-schemes offer a viable alternative, but sluggish mediator kinetics and interfacial side reactions impede their construction. Here we report a stable Z-scheme system integrating n-type CdS and BiVO? with a [Fe(CN)?]??/[Fe(CN)?]?? mediator, achieving 10.2% apparent quantum yield at 450?nm with stoichiometric H?/O? evolution. High activity reflects synergies between Pt@CrOx and Co3O4 cocatalysts on CdS, and cobalt-directed facet asymmetry in BiVO?, resulting in matched kinetics for hydrogen and oxygen evolution in a reversible mediator solution. Stability is dramatically improved through coating CdS and BiVO4 with different oxides to inhibit Fe4[Fe(CN)6]3 precipitation and deactivation by a hitherto unrecognized mechanism. Separate hydrogen and oxygen production is also demonstrated in a two-compartment reactor under visible light and ambient conditions. This work unlocks the long-sought potential of n-type sulfides for efficient, durable and safe solar-driven hydrogen production. en-copyright= kn-copyright= en-aut-name=LuoHaolin en-aut-sei=Luo en-aut-mei=Haolin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiuZhixi en-aut-sei=Liu en-aut-mei=Zhixi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LvHaifeng en-aut-sei=Lv en-aut-mei=Haifeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=VequizoJunie Jhon M. en-aut-sei=Vequizo en-aut-mei=Junie Jhon M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhengMengting en-aut-sei=Zheng en-aut-mei=Mengting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HanFeng en-aut-sei=Han en-aut-mei=Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YeZhen en-aut-sei=Ye en-aut-mei=Zhen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamakataAkira en-aut-sei=Yamakata en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShangguanWenfeng en-aut-sei=Shangguan en-aut-mei=Wenfeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LeeAdam F. en-aut-sei=Lee en-aut-mei=Adam F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WuXiaojun en-aut-sei=Wu en-aut-mei=Xiaojun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KazunariDomen en-aut-sei=Kazunari en-aut-mei=Domen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=LuJun en-aut-sei=Lu en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=JiangZhi en-aut-sei=Jiang en-aut-mei=Zhi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University kn-affil= affil-num=2 en-affil=Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University kn-affil= affil-num=3 en-affil=State Key Laboratory of Precision and Intelligent Chemistry, School of Chemistry and Material Sciences, and Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), University of Science and Technology of China kn-affil= affil-num=4 en-affil=Institute of Aqua Regeneration, Shinshu University kn-affil= affil-num=5 en-affil=College of Chemical and Biological Engineering, Zhejiang University kn-affil= affil-num=6 en-affil=Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University kn-affil= affil-num=7 en-affil=Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University kn-affil= affil-num=8 en-affil=Faculty of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University kn-affil= affil-num=10 en-affil=Centre for Catalysis and Clean Energy, School of Environment and Science, Griffith University kn-affil= affil-num=11 en-affil=State Key Laboratory of Precision and Intelligent Chemistry, School of Chemistry and Material Sciences, and Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), University of Science and Technology of China kn-affil= affil-num=12 en-affil=Institute of Aqua Regeneration, Shinshu University kn-affil= affil-num=13 en-affil=College of Chemical and Biological Engineering, Zhejiang University kn-affil= affil-num=14 en-affil=Research Center for Combustion and Environment Technology, Shanghai Jiao Tong University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=6 article-no= start-page=dsaf030 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MedakaBase as a unified genomic resource platform for medaka fish biology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Medaka, a group of small, mostly freshwater fishes in the teleost order Beloniformes, includes the rice fish Oryzias latipes, a useful model organism studied in diverse biological fields. Chromosome-scale genome sequences of the Hd-rR strain of this species were obtained in 2007, and its improved version has facilitated various genome-wide studies. However, despite its widespread utility, omics data for O. latipes are dispersed across various public databases and lack a unified platform. To address this, the medaka section of the National Bioresource Project (NBRP) of Japan established a genome informatics team in 2022 tasked with providing various in silico solutions for bench biologists. This initiative led to the launch of MedakaBase (https://medakabase.nbrp.jp), a web server that enables gene-oriented analysis including exhaustive sequence similarity searches. MedakaBase also provides on-demand browsing of diverse genome-wide datasets, including tissue-specific transcriptomes and intraspecific genomic variations, integrated with gene models from different sources. Additionally, the platform offers gene models optimized for single-cell transcriptome analysis, which often requires coverage of the 3′ untranslated region (UTR) of transcripts. Currently, MedakaBase provides genome-wide data for seven Oryzias species, including original data for O. mekongensis and O. luzonensis produced by the NBRP team. This article outlines technical details behind the data provided by MedakaBase. en-copyright= kn-copyright= en-aut-name=MorikamiKenji en-aut-sei=Morikami en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanizawaYasuhiro en-aut-sei=Tanizawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YaguraMasaru en-aut-sei=Yagura en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoMika en-aut-sei=Sakamoto en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawamotoShoko en-aut-sei=Kawamoto en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraYasukazu en-aut-sei=Nakamura en-aut-mei=Yasukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamaguchiKatsushi en-aut-sei=Yamaguchi en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShigenobuShuji en-aut-sei=Shigenobu en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NaruseKiyoshi en-aut-sei=Naruse en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KurakuShigehiro en-aut-sei=Kuraku en-aut-mei=Shigehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=2 en-affil=Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=3 en-affil=Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=4 en-affil=Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=5 en-affil=Department of Genetics, Sokendai (Graduate University for Advanced Studies) kn-affil= affil-num=6 en-affil=Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems kn-affil= affil-num=7 en-affil=Trans-Omics Facility, National Institute for Basic Biology kn-affil= affil-num=8 en-affil=Trans-Omics Facility, National Institute for Basic Biology kn-affil= affil-num=9 en-affil=Laboratory of Bioresources, National Institute for Basic Biology, National Institutes of Natural Sciences kn-affil= affil-num=10 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=11 en-affil=Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems kn-affil= en-keyword=medaka kn-keyword=medaka en-keyword=comparative genomics kn-keyword=comparative genomics en-keyword=genome browser kn-keyword=genome browser en-keyword=MedakaBase kn-keyword=MedakaBase en-keyword=Beloniformes kn-keyword=Beloniformes END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=1 article-no= start-page=ycaf192 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Proliferation of a bloom-forming phytoplankton via uptake of polyphosphate-accumulating bacteria under phosphate-limiting conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Harmful algal blooms negatively impact the ecosystem and fisheries in affected areas. Eutrophication is a major factor contributing to bloom occurrence, and phosphorus is particularly important in limiting the growth of bloom-forming algae. Although algae efficiently utilize orthophosphate (Pi) as a phosphorous source over other molecular forms, Pi is often limited in the marine environment. While uptake and utilization of soluble inorganic and organic phosphorous by bloom-forming algae has been extensively studied, the details of geochemical and biological phosphorous cycling remain to be elucidated. Here, we report for the first time that the bloom-forming alga Heterosigma akashiwo can phagocytose bacteria and grow under phosphate-depleted conditions. The addition of Vibrio comitans to Pi-depleted H. akashiwo enabled the alga propagate to high cell densities, whereas other bacterial strains had only a minor effect. Importantly, V. comitans accumulates polyphosphate?a linear polymer of Pi?at high levels. The extent of algal proliferation induced by the addition of Vibrio species and polyphosphate-accumulating Escherichia coli correlated strongly with their polyphosphate content, indicating that bacterial polyphosphate served as an alternative PO43? source for H. akashiwo. The direct uptake of polyphosphate-accumulating bacteria through algal phagocytosis may represent a novel biological phosphorous-cycling pathway in marine ecosystems. The role of polyphosphate-accumulating marine bacteria as a hidden phosphorous source required for bloom formation warrants further investigation. en-copyright= kn-copyright= en-aut-name=FukuyamaSeiya en-aut-sei=Fukuyama en-aut-mei=Seiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UsamiFumiko en-aut-sei=Usami en-aut-mei=Fumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirotaRyuichi en-aut-sei=Hirota en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=OharaShizuka en-aut-sei=Ohara en-aut-mei=Shizuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoKen en-aut-sei=Kondo en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GomibuchiYuki en-aut-sei=Gomibuchi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YasunagaTakuo en-aut-sei=Yasunaga en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OndukaToshimitsu en-aut-sei=Onduka en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KurodaAkio en-aut-sei=Kuroda en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KoikeKazuhiko en-aut-sei=Koike en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UekiShoko en-aut-sei=Ueki en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Integrated Sciences for Life, Hiroshima University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Integrated Sciences for Life, Hiroshima University kn-affil= affil-num=6 en-affil=Research Institute of Environment, Agriculture and Fisheries , Osaka Prefecture kn-affil= affil-num=7 en-affil=Department of Physics and Information Technology, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology kn-affil= affil-num=8 en-affil=Department of Physics and Information Technology, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology kn-affil= affil-num=9 en-affil=Hatsukaichi Branch, Fisheries Technology Institute , Fisheries Research and Education Agency kn-affil= affil-num=10 en-affil=Graduate School of Integrated Sciences for Life, Hiroshima University kn-affil= affil-num=11 en-affil=Graduate School of Integrated Sciences for Life, Hiroshima University kn-affil= affil-num=12 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e21664 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251014 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Biologically-Architected Wear and Damage-Resistant Nanoparticle Coating From the Radular Teeth of Cryptochiton stelleri en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nature utilizes simple building blocks to construct mechanically robust materials that demonstrate superior performance under extreme conditions. These exquisite structures result from the controlled synthesis and hierarchical assembly of nanoscale organic and mineral components that have provided critical evolutionary advantages to ensure survival. One such example is the ultrahard radular teeth found in mollusks, which are used to scrape against rock to feed on algae. Here, it is reported that the leading edges of these teeth consist of a wear-resistant coating that is comprised of densely packed ?65 nm magnetic nanoparticles integrated within an organic matrix of chitin and protein. These mesocrystalline magnetite-based structures are assembled from smaller, highly aligned nanocrystals with inter/intracrystalline organics introduced during the crystallization process. Nanomechanical testing reveals that this multi-scale, nano-architected coating has a combination of increased hardness and a slight decrease in modulus versus geologic magnetite provides the surface of the chiton tooth with superior abrasion resistance. The mesocrystalline structures fracture at primary domain interfaces, corroborated by computational models, providing significant toughening to the tooth under extreme contact stresses. The design features revealed provide insight for the design and fabrication of next-generation advanced wear- and impact-resistant coatings for tooling, machinery, wind turbines, armor, etc. en-copyright= kn-copyright= en-aut-name=WangTaifeng en-aut-sei=Wang en-aut-mei=Taifeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChenYu en-aut-sei=Chen en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SarmientoEzra en-aut-sei=Sarmiento en-aut-mei=Ezra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaoTaige en-aut-sei=Hao en-aut-mei=Taige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ArakakiAtsushi en-aut-sei=Arakaki en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NemotoMichiko en-aut-sei=Nemoto en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZavattieriPablo en-aut-sei=Zavattieri en-aut-mei=Pablo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KisailusDavid en-aut-sei=Kisailus en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Materials Science and Engineering, University of California kn-affil= affil-num=2 en-affil=Lyles School of Civil and Construction Engineering, Purdue University kn-affil= affil-num=3 en-affil=Department of Materials Science and Engineering, University of California kn-affil= affil-num=4 en-affil=Materials and Manufacturing Technologies Program, University of California kn-affil= affil-num=5 en-affil=Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Lyles School of Civil and Construction Engineering, Purdue University kn-affil= affil-num=8 en-affil=Department of Materials Science and Engineering, University of California kn-affil= en-keyword=biomineralization kn-keyword=biomineralization en-keyword=coatings kn-keyword=coatings en-keyword=damage tolerance kn-keyword=damage tolerance en-keyword=magnetite kn-keyword=magnetite en-keyword=mesocrystals kn-keyword=mesocrystals END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=1 article-no= start-page=219 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Does perioperative discontinuation of anti-rheumatic drugs increase postoperative complications in orthopedic surgery for rheumatoid arthritis? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective This study aimed to investigate whether discontinuation of biological or targeted synthetic antirheumatic disease-modifying drugs (bDMARDs or tsDMARDs) influences the incidence of postoperative complications in patients with rheumatoid arthritis (RA) undergoing orthopedic surgery.
Methods A retrospective multicenter cohort study including patients receiving bDMARDs or tsDMARDs who underwent orthopedic surgery was conducted. Data collected encompassed the duration of drug discontinuation and postoperative adverse events, such as delayed wound healing, surgical site infection (SSI), disease flare-ups, and mortality. The association between drug discontinuation and these outcomes was analyzed. Multivariate analyses were conducted to identify potential risk factors for these events.
Results A total of 2,060 cases were initially enrolled. After applying inclusion and exclusion criteria, data from 1,953 patients were analyzed. No significant differences were observed between the groups regarding delayed wound healing, SSI, or mortality. However, the incidence of disease flare-ups was substantially higher in the drug discontinuation group and in the interleukin (IL)-6 inhibitor group. Multivariate analysis identified that tumor necrosis factor α and IL-6 inhibitor use was associated with a higher risk of delayed wound healing relative to T-cell function modifiers.
Conclusion In orthopedic surgery for patients with RA, maintaining the standard or the half of administration interval of bDMARD appears safe in the preoperative period. However, the drug discontinuation may increase the risk of postoperative flare-ups, particularly with IL-6 inhibitors. In addition, T-cell function modifiers may be associated with a lower risk of delayed wound healing, suggesting their safety profile in this context. en-copyright= kn-copyright= en-aut-name=ItoHiromu en-aut-sei=Ito en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaHajime en-aut-sei=Ishikawa en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujiShigeyoshi en-aut-sei=Tsuji en-aut-mei=Shigeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MochizukiTakeshi en-aut-sei=Mochizuki en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EbinaKosuke en-aut-sei=Ebina en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KojimaToshihisa en-aut-sei=Kojima en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumotoTakumi en-aut-sei=Matsumoto en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KubotaAyako en-aut-sei=Kubota en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakajimaArata en-aut-sei=Nakajima en-aut-mei=Arata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KanekoAtsushi en-aut-sei=Kaneko en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsushitaIsao en-aut-sei=Matsushita en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HaraRyota en-aut-sei=Hara en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakurabaKoji en-aut-sei=Sakuraba en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=AkasakiYukio en-aut-sei=Akasaki en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsubaraTsukasa en-aut-sei=Matsubara en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MochidaYuichi en-aut-sei=Mochida en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KanbeKatsuaki en-aut-sei=Kanbe en-aut-mei=Katsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NakagawaNatsuko en-aut-sei=Nakagawa en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MurataKoichi en-aut-sei=Murata en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MomoharaShigeki en-aut-sei=Momohara en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Kurashiki Central Hospital kn-affil= affil-num=2 en-affil=Department of Rheumatology, Niigata Rheumatic Center kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Osaka Minami Medical Center kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, International University of Health and Welfare kn-affil= affil-num=5 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Kamagaya General Hospital kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Osaka University Faculty of Medicine Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Nagoya University Hospital kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, University of Tokyo kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Toho University Omori Medical Center kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery and Rehabilitation, Toho University Sakura Medical Center kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Nagoya Medical Center kn-affil= affil-num=13 en-affil=Department of Rehabilitation Medicine, Kanazawa Medical University kn-affil= affil-num=14 en-affil=The Center for Rheumatic Diseases, Nara Medical University kn-affil= affil-num=15 en-affil=Department of Orthopaedic Surgery, Kyushu Medical Center kn-affil= affil-num=16 en-affil=Department of Orthopaedic Surgery, Kyushu University kn-affil= affil-num=17 en-affil=Department of Orthopaedic Surgery, Matsubara Mayflower Hospital kn-affil= affil-num=18 en-affil=Department of Orthopaedic Surgery, Yokohama City University Medical Center kn-affil= affil-num=19 en-affil=Department of Orthopaedic Surgery, Nippori Orthopaedics and Rheumatic Clinic kn-affil= affil-num=20 en-affil=Department of Orthopaedic Surgery, Kakogawa Medical Center kn-affil= affil-num=21 en-affil=Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Endowed Course for Advanced Therapy for Musculoskeletal Disorders, Keio University School of Medicine kn-affil= en-keyword=Rheumatoid arthritis kn-keyword=Rheumatoid arthritis en-keyword=Orthopaedic surgery kn-keyword=Orthopaedic surgery en-keyword=DMARD kn-keyword=DMARD en-keyword=Perioperative complications kn-keyword=Perioperative complications END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=166 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PEGylation of liposome-encapsulated midazolam does not improve the bioavailability of midazolam when administered orally en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Liposomes are closed vesicles made of the same phospholipid bilayer as biological membranes and are capable of containing drugs, and so they have been investigated as useful drug carriers for drug delivery. We previously developed liposome-encapsulated midazolam (LE-midazolam) for oral administration, but midazolam is metabolized in the liver, and for clinical use the encapsulation of the liposomes needed to be improved to increase the bioavailability of midazolam. The surfaces of pharmaceutical liposomes are generally coated with polyethylene glycol (PEGylation) because it prevents their capture by phagocytes and helps them to avoid the reticuloendothelial system. Therefore, we considered that PEGylation could reduce the metabolism of orally administered encapsulated midazolam in the liver.
Methods Midazolam solution, LE-midazolam solution, and PEGylated liposome-encapsulated midazolam (PEG-LE-midazolam) solution were prepared, and the characteristics of the liposomes in these solutions were evaluated. Furthermore, these solutions were orally administered to rabbits, and the resultant plasma midazolam concentrations were measured. The effects of the PEGylation of LE-midazolam on the plasma concentration and bioavailability of orally administered midazolam were also evaluated.
Results The PEG-LE-midazolam solution contained a higher percentage of larger liposomes than the LE-midazolam solution. The area under the concentration-time curve (AUC) of the LE-midazolam solution was significantly higher than that of the midazolam solution, but there was no difference between the AUC values of the PEG-LE-midazolam and midazolam solutions.
Conclusions These findings suggest that liposome encapsulation may reduce the first-pass effect following oral administration, but PEGylation is not expected to improve the bioavailability of orally administered midazolam. en-copyright= kn-copyright= en-aut-name=NishiokaYukiko en-aut-sei=Nishioka en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LuYanyin en-aut-sei=Lu en-aut-mei=Yanyin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=MiyakeSaki en-aut-sei=Miyake en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujimotoMaki en-aut-sei=Fujimoto en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Hamaoka-InoueMidori en-aut-sei=Hamaoka-Inoue en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanimuraHiroshi en-aut-sei=Tanimura en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UjitaHitomi en-aut-sei=Ujita en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 ORCID= affil-num=1 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dental Anesthesiology, Okayama University Hospital 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, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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= affil-num=8 en-affil=Department of Dental Anesthesiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=PEGylation kn-keyword=PEGylation en-keyword=Liposome kn-keyword=Liposome en-keyword=Midazolam kn-keyword=Midazolam en-keyword=Oral administration kn-keyword=Oral administration en-keyword=Bioavailability kn-keyword=Bioavailability END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=12 article-no= start-page=1455 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of ROS and NO in Plant Responses to Individual and Combined Salt Stress and Waterlogging en-subtitle= kn-subtitle= en-abstract= kn-abstract=During the climate change era, plants are increasingly exposed to multiple environmental challenges occurring simultaneously or sequentially. Among these, salt stress and waterlogging are two major factors that severely constrain crop productivity worldwide and often occur together. To survive under such conditions, plants have evolved sophisticated systems to scavenge harmful levels of reactive oxygen species (ROS). Despite their cytotoxic potential, ROS also act as key signaling molecules that interact with nitric oxide (NO), Ca2+, protein kinases, ion homeostasis pathways, and plant hormones. These signaling and acclimatory mechanisms are closely associated with the functions of energy-regulating organelles?chloroplasts and mitochondria?which are major sources of ROS under both individual and combined stresses. While many of these responses are shared between salt stress, waterlogging and their combination, it is likely that specific signaling mechanisms are uniquely activated when both stresses occur together?mechanisms that cannot be inferred from responses to each stress alone. Such specificity may depend on precise coordination among organelle-derived signals and the tight regulation of their cross-communication. Within this network, ROS and NO likely serve as central hubs, fine-tuning the integration of multiple signaling pathways that enable plants to adapt to complex and fluctuating stress environments. en-copyright= kn-copyright= en-aut-name=AneeTaufika Islam en-aut-sei=Anee en-aut-mei=Taufika Islam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SewelamNasser A. en-aut-sei=Sewelam en-aut-mei=Nasser A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BautistaNonnatus S. en-aut-sei=Bautista en-aut-mei=Nonnatus S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirayamaTakashi en-aut-sei=Hirayama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University kn-affil= affil-num=2 en-affil=Botany Department, Faculty of Science, Tanta University kn-affil= affil-num=3 en-affil=Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Ba?os kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University kn-affil= en-keyword=chloroplasts kn-keyword=chloroplasts en-keyword=mitochondria kn-keyword=mitochondria en-keyword=nitric oxide (NO) kn-keyword=nitric oxide (NO) en-keyword=reactive oxygen species (ROS) kn-keyword=reactive oxygen species (ROS) en-keyword=salt stress kn-keyword=salt stress en-keyword=stress combination waterlogging kn-keyword=stress combination waterlogging END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=変性タンパク質の化学修飾による可溶化技術を利用した生理活性球状タンパク質生産法の開発 kn-title=Development of a production method for biologically active globular proteins through chemical modification-based solubilization of denatured proteins en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KIMURAShuichiro en-aut-sei=KIMURA en-aut-mei=Shuichiro kn-aut-name=木村修一郎 kn-aut-sei=木村 kn-aut-mei=修一郎 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama university kn-affil=岡山大学大学院自然科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=腫瘍周囲組織が口腔扁平上皮癌の生物学的性格に与える影響 kn-title=The Origin of Stroma Influences the Biological Characteristics of Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OMORIHaruka en-aut-sei=OMORI en-aut-mei=Haruka kn-aut-name=大森悠加 kn-aut-sei=大森 kn-aut-mei=悠加 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=786 cd-vols= no-issue= article-no= start-page=152753 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hydrogen-rich gas enhances mitochondrial membrane potential and respiratory function recovery in Caco-2 cells post-ischemia-reperfusion injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Ischemia-reperfusion (I/R) injury induces oxidative stress, leading to damage in highly susceptible intestinal tissues. Molecular hydrogen (H2) has shown therapeutic potential in I/R injuries, with our prior research showing its efficacy in improving outcomes in rat intestinal transplantation models. However, its impact on mitochondrial function remain insufficiently understood. This study aims to elucidate how H2 modulates mitochondrial function impaired by I/R injury.
Methods: To assess the effects of H2 on I/R injury, cells were divided into three groups: a control group, a hypoxic group (99 % N2, 1 % O2, without H2 for 3, 6, or 24 h), and a hypoxic-H2 group (99 % H2, 1 % O2, for the same durations). After treatment, cells were reoxygenated under normoxic conditions (21 % O2) for 1, 2, 4, or 6 h. Mitochondrial membrane potential, oxygen consumption, and ATP production were measured. Reactive oxygen species production and apoptotic and metabolic regulators were also assessed.
Results: H2 markedly promoting mitochondrial recovery following I/R injury, by enhancing ATP production, restoring mitochondrial membrane potential, and improving oxygen consumption. It also reduced ROS levels and suppressed pro-apoptotic signaling. Notably, H2 suppressed the expression of HIF1α and PDK1, suggesting that H2 may act upstream of hypoxia-driven signaling pathways. These changes promoted oxidative phosphorylation and overall cellular function during reperfusion.
Conclusions: Our findings reveal that H2 therapy supports mitochondrial function, suppresses ROS, and modulates hypoxia-driven pathways in I/R injury. These insights advance the understanding of H2's potential in addressing I/R injury and provide a foundation for its application in other hypoxia-related conditions. en-copyright= kn-copyright= en-aut-name=SeyaMizuki en-aut-sei=Seya en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MengYing en-aut-sei=Meng en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshinoriKosaki en-aut-sei=Yoshinori en-aut-mei=Kosaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WatanabeAkihiro en-aut-sei=Watanabe en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaTaihei en-aut-sei=Yamada en-aut-mei=Taihei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University kn-affil= affil-num=10 en-affil=Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University kn-affil= affil-num=11 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Intestinal ischemia-reperfusion injury kn-keyword=Intestinal ischemia-reperfusion injury en-keyword=Molecular hydrogen kn-keyword=Molecular hydrogen en-keyword=Hydrogen gas therapy kn-keyword=Hydrogen gas therapy en-keyword=Caco-2 cells kn-keyword=Caco-2 cells en-keyword=Mitochondrial function kn-keyword=Mitochondrial function en-keyword=Hypoxia-inducible factor-1α (HIF1α) kn-keyword=Hypoxia-inducible factor-1α (HIF1α) END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002079 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Virus taxonomy proposal summaries: a searchable and citable resource to disseminate virus taxonomy advances en-subtitle= kn-subtitle= en-abstract= kn-abstract=Taxonomic classification of cellular organisms requires the publication of descriptions and proposed names of species and the deposition of specimens. Virus taxonomy is developed through a different system of annual submission of formal taxonomy proposals (TPs) that can be submitted by anyone but are typically prepared by a study group appointed by the International Committee on Taxonomy of Viruses (ICTV) and consisting of experts on a particular group of viruses. These are initially evaluated by an expert subcommittee and by the executive committee (EC) of the ICTV. EC-approved TPs are then submitted for evaluation and a ratification vote by the wider ICTV membership. Following ratification, the new taxonomy is annually updated in the Master Species List, associated databases and bioinformatic resources. The process is consistent, creates traceability in assignments and supports a fully evaluated, hierarchical classification and nomenclature of all taxonomic ranks from species to realms. The structure also facilitates large-scale and coordinated changes to virus taxonomy, such as the recent introduction of a binomial species nomenclature.
TPs are available on the ICTV website after ratification, but they are not indexed in bibliographic databases and are not easily cited. Authors of TPs do not receive citation credit for adopted proposals, and their voluntary contributions are largely invisible in the published literature. For greater visibility of TPs and their authors, the ICTV will commence the annual publication of summaries of all TPs from each ICTV subcommittee. These summaries will provide a searchable compendium of all annual taxonomy changes and additions as well as direct links to the Master Species List and other ICTV bioinformatic resources. Their publication will provide due credit and citations for their authors, form the basis for disseminating taxonomy decisions and promote greater visibility and accessibility to taxonomy changes for the virology community. en-copyright= kn-copyright= en-aut-name=MayneRichard en-aut-sei=Mayne en-aut-mei=Richard kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SimmondsPeter en-aut-sei=Simmonds en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SmithDonald B. en-aut-sei=Smith en-aut-mei=Donald B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AdriaenssensEvelien M. en-aut-sei=Adriaenssens en-aut-mei=Evelien M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LefkowitzElliot J. en-aut-sei=Lefkowitz en-aut-mei=Elliot J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OksanenHanna M. en-aut-sei=Oksanen en-aut-mei=Hanna M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZerbiniFrancisco Murilo en-aut-sei=Zerbini en-aut-mei=Francisco Murilo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Alfenas-ZerbiniPoliane en-aut-sei=Alfenas-Zerbini en-aut-mei=Poliane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AylwardFrank O en-aut-sei=Aylward en-aut-mei=Frank O kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Freitas-Ast?aJuliana en-aut-sei=Freitas-Ast?a en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HendricksonR. Curtis en-aut-sei=Hendrickson en-aut-mei=R. Curtis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HughesHolly R. en-aut-sei=Hughes en-aut-mei=Holly R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=?obockaMa?gorzata en-aut-sei=?obocka en-aut-mei=Ma?gorzata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MushegianArcady R. en-aut-sei=Mushegian en-aut-mei=Arcady R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=PenzesJudit en-aut-sei=Penzes en-aut-mei=Judit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=Mu?ozAlejandro Reyes en-aut-sei=Mu?oz en-aut-mei=Alejandro Reyes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=RobertsonDavid L. en-aut-sei=Robertson en-aut-mei=David L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=RouxSimon en-aut-sei=Roux en-aut-mei=Simon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=RubinoLuisa en-aut-sei=Rubino en-aut-mei=Luisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=SabanadzovicSead en-aut-sei=Sabanadzovic en-aut-mei=Sead kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TurnerDann en-aut-sei=Turner en-aut-mei=Dann kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=Van DoorslaerKoenraad en-aut-sei=Van Doorslaer en-aut-mei=Koenraad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=VarsaniArvind en-aut-sei=Varsani en-aut-mei=Arvind kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Nuffield Department of Medicine, University of Oxford kn-affil= affil-num=2 en-affil=Nuffield Department of Medicine, University of Oxford kn-affil= affil-num=3 en-affil=Nuffield Department of Medicine, University of Oxford kn-affil= affil-num=4 en-affil=Quadram Institute Bioscience kn-affil= affil-num=5 en-affil=Department of Microbiology, University of Alabama at Birmingham kn-affil= affil-num=6 en-affil=Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki kn-affil= affil-num=7 en-affil=Departamento de Fitopatologia/BIOAGRO, Universidade Federal de Vi?osa kn-affil= affil-num=8 en-affil=Departamento de Microbiologia, Universidade Federal de Vi?osa kn-affil= affil-num=9 en-affil=Department of Biological Sciences, Virginia Tech kn-affil= affil-num=10 en-affil=Embrapa Cassava and Fruits, Cruz das Almas kn-affil= affil-num=11 en-affil=Department of Microbiology, University of Alabama at Birmingham kn-affil= affil-num=12 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=13 en-affil=Institut Pasteur, Universit? Paris Cit?, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=14 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=15 en-affil=Institute of Biochemistry and Biophysics of the Polish Academy of Sciences kn-affil= affil-num=16 en-affil=Division of Molecular and Cellular Biosciences, National Science Foundation kn-affil= affil-num=17 en-affil=Institute for Quantitative Biomedicine, Rutgers University kn-affil= affil-num=18 en-affil=Departamento de Ciencias Biol?gicas, Universidad de los Andes kn-affil= affil-num=19 en-affil=MRC-University of Glasgow Centre for Virus Research kn-affil= affil-num=20 en-affil=Department of Energy, Joint Genome Institute, Lawrence Berkeley National Laboratory kn-affil= affil-num=21 en-affil=Consiglio Nazionale delle Ricerche, Istituto per la Protezione Sostenibile delle Piante, Sede Secondaria di Bari kn-affil= affil-num=22 en-affil=Department of Agricultural Science and Plant Protection, Mississippi State University kn-affil= affil-num=23 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=24 en-affil=Molecular Biology, University of the West of England kn-affil= affil-num=25 en-affil=Department of Immunobiology, School of Animal and Comparative Biomedical Sciences, BIO5 Institute, University of Arizona Cancer Center kn-affil= affil-num=26 en-affil=The Biodesign Center for Fundamental and Applied Microbiomics, School of Life Sciences, Center for Evolution and Medicine, Arizona State University kn-affil= en-keyword=ICTV kn-keyword=ICTV en-keyword=master species list kn-keyword=master species list en-keyword=taxonomy proposal kn-keyword=taxonomy proposal en-keyword=virus taxonomy kn-keyword=virus taxonomy END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=1 article-no= start-page=e70258 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Early-life exposures and child health outcomes: A narrative review of LSN21 research in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The Longitudinal Survey of Newborns in the 21st Century (LSN21) tracks two Japanese national birth cohorts?2001 (baseline n?=?47,010) and 2010 (n?=?38,554)?from infancy through young adulthood, capturing parenting practices and family environments. Most studies analyze single exposures or outcomes. We conducted a narrative review summarizing the findings published by the Okayama University group on diverse health and developmental outcomes.
Methods: We reviewed 59 LSN21 papers (2013?2025), extracting data on exposures, outcomes, and methods. Evidence was categorized into four exposure types (infant feeding, sleep, environmental, and perinatal) and three outcome domains (obesity, allergies/respiratory tract infections, and neurobehavioral development), including cohort comparisons.
Results: Exclusive breastfeeding was associated with a lower obesity risk at ages 7 (adjusted odds ratio 0.55, 95% confidence interval 0.39?0.78) and 15, later puberty, and fewer hospitalizations. Short or irregular sleep before age 3 was linked to behavioral problems and injuries. Maternal smoking and prenatal air pollution were associated with respiratory conditions and developmental challenges. Preterm birth and small-for-gestational-age predicted delays, especially without catch-up growth by age 2. Pneumococcal vaccination likely contributed to declining otitis media after 2010. Additional findings included associations between outdoor play and reduced obesity risk, and complex relationships between breastfeeding and food allergies that varied by infantile eczema status.
Conclusions: LSN21 findings highlight modifiable early-life factors (breastfeeding, sleep patterns, and smoke-free environments) and identify preterm and growth-restricted children for priority monitoring. While LSN21's strength lies in longitudinal social assessments, complementary perspectives from other Japanese cohorts could enhance understanding of biological mechanisms and intergenerational effects. en-copyright= kn-copyright= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuoRumi en-aut-sei=Matsuo en-aut-mei=Rumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamuraYuka en-aut-sei=Yamamura en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsugeTakahiro en-aut-sei=Tsuge en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KadowakiTomoka en-aut-sei=Kadowaki en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UraguchiKensuke en-aut-sei=Uraguchi en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TamaiKei en-aut-sei=Tamai en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraKazue en-aut-sei=Nakamura en-aut-mei=Kazue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakeuchiAkihito en-aut-sei=Takeuchi en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Neonatology, NHO Okayama Medical Center kn-affil= affil-num=10 en-affil=Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=breastfeeding kn-keyword=breastfeeding en-keyword=child health kn-keyword=child health en-keyword=environmental exposure kn-keyword=environmental exposure en-keyword=longitudinal studies kn-keyword=longitudinal studies en-keyword=perinatal kn-keyword=perinatal END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=10 article-no= start-page=1483 end-page=1493 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biologics and Small‐Molecule Therapies in Netherton Syndrome: A Comprehensive Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Netherton syndrome (NS) is a rare congenital ichthyosis caused by loss-of-function mutations in the SPINK5 gene, leading to defective expression of the serine protease inhibitor LEKTI. Dysregulated epidermal protease activity results in impaired skin barrier function and chronic inflammation, accompanied by complex immune profiles. NS patients commonly show activation of the inflammatory axis, centered on IL-17 and IL-36, in the skin and blood, and show a psoriasis-like shift to Th17. Conversely, the immune profile differs depending on the clinical type, with ichthyosis linearis circumflexa type characterized by complement activation and Th2-type allergic responses, and scaly erythroderma type characterized by a type I IFN signature and Th9-type allergic responses. While symptomatic treatments such as emollients and topical corticosteroids have been the mainstay of care, recent advances have opened new therapeutic avenues involving biologic agents and oral small-molecule immunomodulators. This review provides a comprehensive overview of the current clinical landscape and future directions of biologics (e.g., dupilumab, secukinumab, ustekinumab) and small-molecule therapies (e.g., JAK inhibitors such as tofacitinib, baricitinib, and upadacitinib) in the treatment of NS. Though evidence remains limited to case reports and small series, preliminary data suggest that cytokine-targeted interventions?particularly those inhibiting IL-4, IL-13, IL-17, IL-36, and JAK pathways?may offer tangible clinical benefits. Well-designed clinical trials and mechanistic investigations are crucial to establishing their place in NS management. en-copyright= kn-copyright= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MukaiTomoyuki en-aut-sei=Mukai en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SunagawaKo en-aut-sei=Sunagawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HasuiKen‐ichi en-aut-sei=Hasui en-aut-mei=Ken‐ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaAnri en-aut-sei=Morita en-aut-mei=Anri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomuraHayato en-aut-sei=Nomura en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=5 article-no= start-page=345 end-page=352 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inhibition of Air-Exposure Stress?Induced Autolysis in Clostridium perfringens by Zn2+ en-subtitle= kn-subtitle= en-abstract= kn-abstract=Clostridium perfringens is a pathogenic anaerobe that causes gas gangrene and food poisoning. Although autolysin-mediated reorganization of the bacterial cell wall is crucial for cell division, excessive autolysin activity induced by stressors can lead to cell lysis. In C. perfringens, air exposure is a significant stressor that causes cell lysis, and Acp (N-acetylglucosaminidase) is known to be a major autolysin. To further facilitate C. perfringens research, a technology to prevent air-induced cell lysis must be developed. This study investigated the role of Acp in air-induced autolysis and explored potential inhibitors that would prevent cell lysis during experimental procedures. Morphological analyses confirmed that Acp functions as an autolysin in C. perfringens, as acpdeficient strains exhibited filamentous growth. The mutants exhibited negligible autolysis under air-exposure stress, confirming the involvement of Acp in the autolytic process. We also evaluated the effects of various divalent cations on Acp activity in vitro and identified Zn2+ as a potent inhibitor. Brief treatment with a Zn2+- containing buffer induced dose-dependent cell elongation and autolysis inhibition in C. perfringens. These findings demonstrate that simple Zn2+ treatment before experiments stabilizes C. perfringens cells, reducing autolysis under aerobic conditions and facilitating various biological studies, except morphological analyses. en-copyright= kn-copyright= en-aut-name=MatsunagaNozomu en-aut-sei=Matsunaga en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EgusaSeira en-aut-sei=Egusa en-aut-mei=Seira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AonoRiyo en-aut-sei=Aono en-aut-mei=Riyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TamaiEiji en-aut-sei=Tamai en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HitusmotoYasuo en-aut-sei=Hitusmoto en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatayamaSeiichi en-aut-sei=Katayama en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=2 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=3 en-affil=Department of Medical Technology, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=4 en-affil=Department of Infectious Disease, College of Pharmaceutical Science, Matsuyama University kn-affil= affil-num=5 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= affil-num=6 en-affil=Department of Life Science, Faculty of Science, Okayama University of Science kn-affil= en-keyword=Clostridium perfringens kn-keyword=Clostridium perfringens en-keyword=autolysin kn-keyword=autolysin en-keyword=zinc kn-keyword=zinc en-keyword=air-exposure autolysis kn-keyword=air-exposure autolysis END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=7 article-no= start-page=1044 end-page=1060 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250527 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oxygen supply is a prerequisite for response to aluminum in cultured cells of tobacco (Nicotiana tabacum) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Responses to aluminum (Al) were investigated in tobacco cells (cell line SL) in a calcium-sucrose solution for up to 24 h under shaking (aerobic) condition. Microarray analysis of upregulated and downregulated genes under Al exposure and following Gene Ontology (GO) enrichment analysis of biological process category revealed only one GO term to be enriched for the upregulated genes, “response to chitin,” annotated with genes encoding transcription factors (NtERF1 and NtMYB3) and MAP kinase (WIPK), and nine GO terms for the downregulated genes, including “cell wall loosening” and “lipid transport,” annotated with genes encoding expansin (NtEXPA4) and lipid transfer protein (LTP)/LTP-like (NtLTP3 and NtEIG-C29), respectively. Al triggered the production of nitric oxide (NO) then reactive oxygen species (ROS). Addition of NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide decreased the levels of NO and a part of the transcriptional changes described above, but increased the levels of ROS and a loss of growth capacity, suggesting a role of the NO to induce the transcriptional changes partly and to repress these toxic responses under Al exposure. Under non-shaking (anaerobic) condition, the cells exhibited upregulation of several hypoxia-responsive genes. The cells exposed to Al exhibited the same level of Al accumulation but much lower levels of the Al responses including NO production, ROS production, a loss of growth capacity, citrate secretion, and a part of the transcriptional changes described above, compared with the cells under shaking condition. These results suggest that coexistence of oxygen with Al is necessary to trigger the Al responses related to toxicity and tolerance. en-copyright= kn-copyright= en-aut-name=TsuchiyaYoshiyuki en-aut-sei=Tsuchiya en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasakiTakayuki en-aut-sei=Sasaki en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoYoko en-aut-sei=Yamamoto en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=aluminum toxicity kn-keyword=aluminum toxicity en-keyword=aluminum-responsive genes kn-keyword=aluminum-responsive genes en-keyword=cell wall loosening kn-keyword=cell wall loosening en-keyword=chitin-responsive genes kn-keyword=chitin-responsive genes en-keyword=dioxygen kn-keyword=dioxygen en-keyword=hypoxia kn-keyword=hypoxia END start-ver=1.4 cd-journal=joma no-vol=40 cd-vols= no-issue=4 article-no= start-page=463 end-page=474 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nationwide diversity of symbolic “city flowers” in Japan is increasing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recognizing and maintaining locally rooted human?nature interactions is essential for utilizing ecosystem services. Although the general public's awareness of biodiversity and ecosystem services has been examined using various proxies, it remains unclear how local governments?key sectors in creating conservation policies?appreciate them within a solid local context. Here, we focused on the “city flower,” an official symbolic species of Japanese cities, as a new proxy for measuring governmental attitudes toward biota and its services. We aimed to capture temporal changes in the awareness of species with locally relevant value at the city government level by examining the changes in city flowers over more than half a century. Data from the official websites of municipalities, including the names, the adoption years, and the reasons for adoption, revealed two major periods of adoption, with a notable increase in species diversity in and after 1993. This increase could be attributed to a recent reduction in bias toward popular flowers and growing interest in alternative, less popular flowers. Analysis of the reasons for adoption suggested that the temporal change in adopted flower species was related to the increasing emphasis on species with an explicit local context, especially those with instrumental value to the city. Our findings indicate the tendency for local governments to increasingly recognize their biocultural backgrounds and the ecosystem services of plants within their regions. The growing awareness of the local governments regarding their biocultural background is a positive sign for the conservation of biodiversity and ecosystem services. en-copyright= kn-copyright= en-aut-name=TsuzukiYoichi en-aut-sei=Tsuzuki en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhsakiHaruna en-aut-sei=Ohsaki en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaguchiYawako W. en-aut-sei=Kawaguchi en-aut-mei=Yawako W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiSayaka en-aut-sei=Suzuki en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaradaShogo en-aut-sei=Harada en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtakeYurie en-aut-sei=Otake en-aut-mei=Yurie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShinoharaNaoto en-aut-sei=Shinohara en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatsuharaKoki R. en-aut-sei=Katsuhara en-aut-mei=Koki R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Health and Environmental Risk Division, National Institute for Environmental Studies kn-affil= affil-num=2 en-affil=Department of Biological Sciences, Tokyo Metropolitan University kn-affil= affil-num=3 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=4 en-affil=Center for Ecological Research, Kyoto University kn-affil= affil-num=5 en-affil=Department of Biology, Graduate School of Science, Osaka City University kn-affil= affil-num=6 en-affil=Center for Ecological Research, Kyoto University kn-affil= affil-num=7 en-affil=Center for Ecological Research, Kyoto University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=awareness of local governments kn-keyword=awareness of local governments en-keyword=biocultural diversity kn-keyword=biocultural diversity en-keyword=ecosystem services kn-keyword=ecosystem services en-keyword=manual web scraping kn-keyword=manual web scraping en-keyword=temporal trend kn-keyword=temporal trend END start-ver=1.4 cd-journal=joma no-vol=118 cd-vols= no-issue=10 article-no= start-page=146 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Duganella hordei sp. nov., Duganella caerulea sp. nov., and Duganella rhizosphaerae sp. nov., isolated from barley rhizosphere en-subtitle= kn-subtitle= en-abstract= kn-abstract=Duganella sp. strains R1T, R57T, and R64T, isolated from barley roots in Japan, are Gram-stain-negative, motile, rod-shaped bacteria. Duganella species abundantly colonized barley roots. Strains R1T, R57T, and R64T were capable of growth at 4 °C, suggesting adaptation to colonize winter barley roots. Strains R57T and R64T formed purple colonies, indicating violacein production, while strain R1T did not. Based on 16S rRNA gene sequence similarities, strains R1T, R57T, and R64T were most closely related to D. violaceipulchra HSC-15S17T (99.10%), D. vulcania FT81WT (99.45%), and D. violaceipulchra HSC-15S17T (99.86%), respectively. Their genome sizes ranged from 7.05 to 7.38 Mbp, and their genomic G+C contents were 64.2?64.7%. The average nucleotide identity and digital DNA?DNA hybridization values between R1T and D. violaceipulchra HSC-15S17T, R57T and D. vulcania FT81WT, R64T and D. violaceipulchra HSC-15S17T were 86.0% and 33.2%, 95.7% and 67.9%, and 92.7% and 52.6%, respectively. Their fatty acids were predominantly composed of C16:0, C17:0 cyclo, and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). Based on their distinct genetic and phenotypic characteristics, and supported by chemotaxonomic analyses, we propose that strains R1T, R57T, and R64T represent novel species within the Duganella genus, for which the names Duganella hordei (type strain R1T?=?NBRC 115982 T?=?DSM 115069 T), Duganella caerulea (type strain R57T?=?NBRC 115983 T?=?DSM 115070 T), and Duganella rhizosphaerae (type strain R64T?=?NBRC 115984 T?=?DSM 115071 T) are proposed. en-copyright= kn-copyright= en-aut-name=KishiroKatsumoto en-aut-sei=Kishiro en-aut-mei=Katsumoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SahinNurettin en-aut-sei=Sahin en-aut-mei=Nurettin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaishoDaisuke en-aut-sei=Saisho en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamajiNaoki en-aut-sei=Yamaji en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamashitaJun en-aut-sei=Yamashita en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MondenYuki en-aut-sei=Monden en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakagawaTomoyuki en-aut-sei=Nakagawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MochidaKeiichi en-aut-sei=Mochida en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TaniAkio en-aut-sei=Tani en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Egitim Fakultesi, Mugla Sitki Kocman University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Applied Biological Sciences, Gifu University kn-affil= affil-num=8 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Barley kn-keyword=Barley en-keyword=Duganella kn-keyword=Duganella en-keyword=Novel species kn-keyword=Novel species en-keyword=Rhizosphere kn-keyword=Rhizosphere END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=10 article-no= start-page=4724 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250515 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Stem Cell Factors BAM1 and WOX1 Suppressing Longitudinal Cell Division of Margin Cells Evoked by Low-Concentration Auxin in Young Cotyledon of Arabidopsis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Highly differentiated tissues and organs play essential biological functions in multicellular organisms. Coordination of organ developmental process with tissue differentiation is necessary to achieve proper development of mature organs, but mechanisms for such coordination are not well understood. We used cotyledon margin cells from Arabidopsis plant as a new model system to investigate cell elongation and cell division during organ growth and found that margin cells endured a developmental phase transition from the “elongation” phase to the “elongation and division” phase at the early stage in germinating seedlings. We also discovered that the stem cell factors BARELY ANY MERISTEM 1 (BAM1) and WUSCHEL-related homeobox1 (WOX1) are involved in the regulation of margin cell developmental phase transition. Furthermore, exogenous auxin treatment (1 nanomolar,nM) promotes cell division, especially longitudinal cell division. This promotion of cell division did not occur in bam1 and wox1 mutants. Based on these findings, we hypothesized a new “moderate auxin concentration” model which emphasizes that a moderate auxin concentration is the key to triggering the developmental transition of meristematic cells. en-copyright= kn-copyright= en-aut-name=JiangYuli en-aut-sei=Jiang en-aut-mei=Yuli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiangJian en-aut-sei=Liang en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangChunyan en-aut-sei=Wang en-aut-mei=Chunyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanLi en-aut-sei=Tan en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawanoYoji en-aut-sei=Kawano en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagawaShingo en-aut-sei=Nagawa en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute for Translational Brain Reaearch, Fudan University kn-affil= affil-num=2 en-affil=Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences kn-affil= en-keyword=BAM1 kn-keyword=BAM1 en-keyword=WOX1 kn-keyword=WOX1 en-keyword=margin cells kn-keyword=margin cells en-keyword=auxin kn-keyword=auxin END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Alternative Approach Based on Skin Electrical Impedance to Determine Transepidermal Water Loss for Skin Barrier Function Assessments en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: The transepidermal water loss (TEWL) has long been measured as an indicator to assess the skin barrier function in dermatological research and clinical practice. However, practical limitations such as time requirement, environmental sensitivity, and measurement complexity hinder the widespread uptake of conventional TEWL measurements in clinical settings and routine monitoring. Consequently, there is a growing need for rapid, robust, and clinically applicable alternatives to conventional TEWL measurements. Here, we present a simple, non-invasive, and time-efficient method based on the skin electrical impedance for skin barrier function assessments.
Methods: The skin electrical impedance, TEWL, stratum corneum (SC) thickness, and SC surface water content of 25 healthy adult participants with no history of dermatological diseases were measured at two adjacent forearm sites: intact site with a normal skin barrier and tape-stripped site with an impaired skin barrier. The measured impedance was used to calculate the SC thickness and surface water content, from which the TEWL was estimated and then compared against the TEWL measured using a Tewameter. The estimation accuracy was evaluated by determining the correlation coefficient (R) and root mean square error (RMSE) between estimated and measured TEWL.
Results: A strong correlation (R?=?0.891) was observed between estimated and measured TEWL, with an RMSE of 6.05 g/m?/h, indicating high accuracy of the proposed method.
Conclusion: This impedance-based method provides accurate estimations of the TEWL, indicating its potential as a practical alternative to conventional TEWL measurements for skin barrier function assessments, particularly in clinical or high-throughput settings. en-copyright= kn-copyright= en-aut-name=UeharaOsamu en-aut-sei=Uehara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraTakao en-aut-sei=Nakamura en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=Transepidermal water loss kn-keyword=Transepidermal water loss en-keyword=Electrical impedance kn-keyword=Electrical impedance en-keyword=Stratum corneum kn-keyword=Stratum corneum en-keyword=Skin barrier kn-keyword=Skin barrier END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=17 article-no= start-page=8145 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250822 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Augmentation of the Benzyl Isothiocyanate-Induced Antiproliferation by NBDHEX in the HCT-116 Human Colorectal Cancer Cell Line en-subtitle= kn-subtitle= en-abstract= kn-abstract=Increased drug metabolism and elimination are prominent mechanisms mediating multidrug resistance (MDR) to not only chemotherapy drugs but also anti-cancer natural products, such as benzyl isothiocyanate (BITC). To evaluate the possibility of combined utilization of a certain compound to overcome this resistance, we focused on glutathione S-transferase (GST)-dependent metabolism of BITC. The pharmacological treatment of a pi-class GST-selective inhibitor, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), significantly increased BITC-induced toxicity in human colorectal cancer HCT-116 cells. However, NBDHEX unexpectedly increased the level of the BITC?glutathione (GSH) conjugate as well as BITC-modified proteins, suggesting that NBDHEX might increase BITC-modified protein accumulation by inhibiting BITC?GSH excretion instead of inhibiting GST. Furthermore, NBDHEX significantly potentiated BITC-induced apoptosis with the enhanced activation of apoptosis-related pathways, such as c-Jun N-terminal kinase and caspase-3 pathways. These results suggested that combination treatment with NBDHEX may be an effective way to overcome MDR with drug efflux and thus induce the biological activity of BITC at lower doses. en-copyright= kn-copyright= en-aut-name=SunRuitong en-aut-sei=Sun en-aut-mei=Ruitong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YanoAina en-aut-sei=Yano en-aut-mei=Aina 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=MunemasaShintaro en-aut-sei=Munemasa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakamuraToshiyuki en-aut-sei=Nakamura en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University 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=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=benzyl isothiocyanate kn-keyword=benzyl isothiocyanate en-keyword=multidrug resistance kn-keyword=multidrug resistance en-keyword=glutathione S-transferase kn-keyword=glutathione S-transferase en-keyword=NBDHEX kn-keyword=NBDHEX en-keyword=apoptosis kn-keyword=apoptosis en-keyword=c-Jun N-terminal kinase kn-keyword=c-Jun N-terminal kinase END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=2503029 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250601 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Polyglycerol‐Grafted Graphene Oxide with pH‐Responsive Charge‐Convertible Surface to Dynamically Control the Nanobiointeractions for Enhanced in Vivo Tumor Internalization en-subtitle= kn-subtitle= en-abstract= kn-abstract=pH-responsive charge-convertible nanomaterials (NMs) ameliorate the treatment of cancer via simultaneously reducing nonspecific interactions during systemic circulation and improving targeted uptake within solid tumors. While promising, little is known about how the pH-responsiveness of charge-convertible NMs directs their interactions with biological systems, leading to compromised performance, including off-target retention and low specificity to tumor cells. In the present study, polyglycerol-grafted graphene oxide bearing amino groups (GOPGNH2) at different densities are reacted with dimethylmaleic anhydride (DMMA), a pH-responsive moiety, to generate a set of charge-convertible GOPGNH-DMMA variants. This permits the assessment of a quantitative correlation between the structure of GOPGNH-DMMA to their pH-responsiveness, their dynamic interactions with proteins and cells, as well as their in vivo biological fate. Through a systematic investigation, it is revealed that GOPGNH115-DMMA prepared from GOPGNH2 with higher amine density experienced fast charge conversion at pH 7.4 to induce non-specific interactions at early stages, whereas GOPGNH60-DMMA and GOPGNH30-DMMA prepared from lower amine density retarded off-target charge conversion to enhance tumor accumulation. Notably, GOPGNH60-DMMA is also associated with enough amounts of proteins under acidic conditions to promote in vivo tumor internalization. The findings will inform the design of pH-responsive NMs for enhanced treatment accuracy and efficacy. en-copyright= kn-copyright= en-aut-name=ZouYajuan en-aut-sei=Zou en-aut-mei=Yajuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BiancoAlberto en-aut-sei=Bianco en-aut-mei=Alberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=charge conversion kn-keyword=charge conversion en-keyword=in vivo tumor internalization kn-keyword=in vivo tumor internalization en-keyword=non-specific interaction kn-keyword=non-specific interaction en-keyword=pH-responsiveness kn-keyword=pH-responsiveness en-keyword=polyglycerol-grafted graphene oxide kn-keyword=polyglycerol-grafted graphene oxide END start-ver=1.4 cd-journal=joma no-vol=48 cd-vols= no-issue=1 article-no= start-page=51 end-page=59 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An Underlying Mechanism for the Altered Hypoglycemic Effects of Nateglinide in Rats with Acute Peripheral Inflammation en-subtitle= kn-subtitle= en-abstract= kn-abstract=The hypoglycemic effects of nateglinide (NTG) were examined in rats with acute peripheral inflammation (API) induced by carrageenan treatment, and the mechanisms accounting for altered hypoglycemic effects were investigated. NTG was administered through the femoral vein in control and API rats, and its plasma concentration profile was characterized. The time courses of the changes in plasma glucose and insulin levels were also examined. Although the plasma concentration profile of NTG in API rats was marginally distinguishable from that in control rats, the hypoglycemic effect of NTG was more persistent in API rats than in control rats. In addition, NTG elevated the plasma level of insulin more intensely in API rats than in control rats. Then, the islets of Langerhans were procured by perfusing the pancreas with collagenase solution in control and API rats, and the pancreatic mRNA expression of preproinsulin (Ins1), as well as that of sulfonylurea receptor ABCC8 (Abcc8), were examined. As a result, the expression of preproinsulin and ABCC8 mRNA increased in API rats. These findings suggest that the hypoglycemic effect of NTG was potentiated in API rats due to increased insulin secretion in the pancreas, which was caused by enhanced preproinsulin synthesis and expression of the sulfonylurea receptor. en-copyright= kn-copyright= en-aut-name=TokoHaruka en-aut-sei=Toko en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OginoManami en-aut-sei=Ogino en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiwakiAkane en-aut-sei=Nishiwaki en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KojinaMoeko en-aut-sei=Kojina en-aut-mei=Moeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AibaTetsuya en-aut-sei=Aiba en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and 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=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=blood sugar kn-keyword=blood sugar en-keyword=inflammation kn-keyword=inflammation en-keyword=insulin kn-keyword=insulin en-keyword=Langerhans islet kn-keyword=Langerhans islet en-keyword=nateglinide kn-keyword=nateglinide END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=14 article-no= start-page=2406 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250721 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Definitions of, Advances in, and Treatment Strategies for Breast Cancer Oligometastasis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oligometastasis represents a clinically relevant state of limited metastatic disease that could be amenable to selected local therapies in carefully chosen patients. Although initial trials such as SABR-COMET demonstrated a survival benefit with aggressive local treatment, breast cancer was underrepresented. Subsequent breast cancer-specific trials, including NRG-BR002, failed to show a clear survival benefit, highlighting uncertainties and the need for further refinement in patient selection and integration with systemic approaches. The definitions of oligometastasis continue to evolve, incorporating radiological, clinical, and biological features. Advances in imaging and molecular profiling suggest that oligometastatic breast cancer might represent a distinct biological subtype, with potential biomarkers including PIK3CA mutations and YAP/TAZ expression. Organ-specific strategies using stereotactic radiotherapy, surgery, and proton therapy have shown favorable local control in certain settings, though their impact on the overall survival remains under investigation. Emerging techniques, including circulating tumor DNA (ctDNA) analysis, are being explored to improve patient selection and disease monitoring. Ongoing trials may provide further insight into the role of local therapy, particularly in hormone receptor-positive or HER2-positive subtypes. Local and systemic strategies need to be carefully coordinated to optimize the outcomes. This review summarizes the current definitions of and evidence and therapeutic considerations for oligometastatic breast cancer and outlines potential future directions. en-copyright= kn-copyright= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamotoShogo en-aut-sei=Nakamoto en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraYuki en-aut-sei=Fujiwara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KosakaMaya en-aut-sei=Kosaka en-aut-mei=Maya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaraharaYuki en-aut-sei=Narahara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiKento en-aut-sei=Fujii en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaedaReina en-aut-sei=Maeda en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoShutaro en-aut-sei=Kato en-aut-mei=Shutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MimataAsuka en-aut-sei=Mimata en-aut-mei=Asuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshiokaRyo en-aut-sei=Yoshioka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuwaharaChihiro en-aut-sei=Kuwahara en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsukiokiTakahiro en-aut-sei=Tsukioki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakahashiYuko en-aut-sei=Takahashi en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwataniTsuguo en-aut-sei=Iwatani en-aut-mei=Tsuguo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TaniokaMaki en-aut-sei=Tanioka en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=oligo-recurrence kn-keyword=oligo-recurrence en-keyword=breast cancer kn-keyword=breast cancer en-keyword=local therapy kn-keyword=local therapy END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=2 article-no= start-page=606 end-page=617 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mechanistic Insights Into Oxidative Response of Heat Shock Factor 1 Condensates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heat shock factor 1 (Hsf1), a hub protein in the stress response and cell fate decisions, senses the strength, type, and duration of stress to balance cell survival and death through an unknown mechanism. Recently, changes in the physical property of Hsf1 condensates due to persistent stress have been suggested to trigger apoptosis, highlighting the importance of biological phase separation and transition in cell fate decisions. In this study, the mechanism underlying Hsf1 droplet formation and oxidative response was investigated through 3D refractive index imaging of the internal architecture, corroborated by molecular dynamics simulations and biophysical/biochemical experiments. We found that, in response to oxidative conditions, Hsf1 formed liquid condensates that suppressed its internal mobility. Furthermore, these conditions triggered the hyper-oligomerization of Hsf1, mediated by disulfide bonds and secondary structure stabilization, leading to the formation of dense core particles in the Hsf1 droplet. Collectively, these data demonstrate how the physical property of Hsf1 condensates undergoes an oxidative transition by sensing redox conditions to potentially drive cell fate decisions. en-copyright= kn-copyright= en-aut-name=KawagoeSoichiro en-aut-sei=Kawagoe en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsusakiMotonori en-aut-sei=Matsusaki en-aut-mei=Motonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MabuchiTakuya en-aut-sei=Mabuchi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgasawaraYuto en-aut-sei=Ogasawara en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshimoriKoichiro en-aut-sei=Ishimori en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaioTomohide en-aut-sei=Saio en-aut-mei=Tomohide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=2 en-affil=Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=3 en-affil=Frontier Research Institute for Interdisciplinary Sciences, Tohoku University kn-affil= affil-num=4 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Chemistry, Faculty of Science, Hokkaido University kn-affil= affil-num=7 en-affil=Institute of Advanced Medical Sciences, Tokushima University kn-affil= en-keyword=heat shock factor 1 kn-keyword=heat shock factor 1 en-keyword=oxidative hyper-oligomerization kn-keyword=oxidative hyper-oligomerization en-keyword=biological phase transition kn-keyword=biological phase transition en-keyword=stress response kn-keyword=stress response en-keyword=biophysics kn-keyword=biophysics END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=10 article-no= start-page=1151 end-page=1159 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=NCF-1 plays a pivotal role in the survival of adenocarcinoma cells of pancreatic and gastric origins en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reactive oxygen species (ROS) play a pivotal biological role in cells, with ROS function differing depending on cellular conditions and the extracellular environment. Notably, ROS act as cytotoxic factors to eliminate infectious pathogens or promote cell death under cellular stress, while also facilitating cell growth (via ROS-sensing pathways) by modifying gene expression. Among ROS-related genes, neutrophil cytosolic factor-1 (NCF-1; p47phox) was identified as a ROS generator in neutrophils. This product is a subunit of a cytosolic NADPH oxidase complex activated in response to pathogens such as bacteria and viruses. NCF-1 has been examined primarily in terms of ROS-production pathways in macrophages and neutrophils; however, the expression of this protein and its biological role in cancer cells remain unclear. Here, we report expression of NCF-1 in pancreatic and gastric cancers, and demonstrate its biological significance in these tumor cells. Abundant expression of NCF-1 was observed in pancreatic adenocarcinoma (PDAC) lines and in patient tissues, as well as in gastric adenocarcinomas. Accumulation of the protein was also detected in the invasive/metastatic foci of these tumors. Unexpectedly, BxPC-3 underwent apoptotic cell death when transfected with a small interfering RNA (siRNA) specific to NCF-1, whereas the cells treated with a control siRNA proliferated in a time-dependent manner. A similar phenomenon was observed in HSC-58, a poorly differentiated gastric adenocarcinoma line. Consequently, the tumor cells highly expressing NCF-1 obtained coincident accumulation of ROS and reduced glutathione (GSH) with expression of glutathione peroxidase 4 (GPX4), a quencher involved in ferroptosis. Unlike the conventional role of ROS as a representative cytotoxic factor, these findings suggest that NCF-1-mediated ROS generation may be required for expansive growth of PDAC and gastric cancers. en-copyright= kn-copyright= en-aut-name=Furuya-IkudeChiemi en-aut-sei=Furuya-Ikude en-aut-mei=Chiemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KittaAkane en-aut-sei=Kitta en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomonobuNaoko en-aut-sei=Tomonobu en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawasakiYoshihiro en-aut-sei=Kawasaki en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= affil-num=2 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= affil-num=5 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Division of Tumor Pathology, NIR-PIT Research Institute, Kansai Medical University kn-affil= en-keyword=NCF-1 (p47phox) kn-keyword=NCF-1 (p47phox) en-keyword=ROS kn-keyword=ROS en-keyword=Cancer kn-keyword=Cancer en-keyword=Tumor growth kn-keyword=Tumor growth en-keyword=Apoptosis kn-keyword=Apoptosis END start-ver=1.4 cd-journal=joma no-vol=239 cd-vols= no-issue= article-no= start-page=113237 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2026 dt-pub=202602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Counting-loss correction procedure of X-ray imaging detectors with consideration for the effective atomic number of biological objects en-subtitle= kn-subtitle= en-abstract= kn-abstract=It is necessary to correct counting loss caused by the pulse pile-up effect and dead time when using energy-resolving photon-counting detectors (ERPCDs) under “high-counting-rate” conditions in medical and/or industrial settings. We aimed to develop a novel counting-loss correction procedure in which biological objects having effective atomic numbers (Zeff values) of 6.5?13.0 are measured with polychromatic X-rays. To correct for counting loss, such a procedure must theoretically estimate the count value of an ideal X-ray spectrum without counting loss. In this study, we estimated the ideal X-ray spectrum by focusing on the following two points: (1) the X-ray attenuation in an object (Zeff values of 6.5?13.0) and (2) the detector response. Virtual materials having intermediate atomic numbers between 6.5 and 13.0 were generated by using a mixture of polymethylmethacrylate (PMMA, Zeff = 6.5) and aluminum (Al, Zeff = 13.0). We then constructed an algorithm that can perform the counting-loss correction based on the object’s true Zeff value. To demonstrate the applicability of our procedure, we analyzed investigational objects consisting of PMMA and Al using a prototype ERPCD system. A fresh fish sample was also analyzed. The Zeff values agree with the theoretical values within an accuracy of Zeff ±1. In conclusion, we have developed a highly accurate procedure for correcting counting losses for the quantitative X-ray imaging of biological objects. en-copyright= kn-copyright= en-aut-name=KimotoNatsumi en-aut-sei=Kimoto en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishigamiRina en-aut-sei=Nishigami en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiDaiki en-aut-sei=Kobayashi en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaedaTatsuya en-aut-sei=Maeda en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GotoSota en-aut-sei=Goto en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanazawaYuki en-aut-sei=Kanazawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatsumataAkitoshi en-aut-sei=Katsumata en-aut-mei=Akitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoShuichiro en-aut-sei=Yamamoto en-aut-mei=Shuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HayashiHiroaki en-aut-sei=Hayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=2 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=3 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=4 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Faculty of Health Science, Kobe Tokiwa University kn-affil= affil-num=7 en-affil=Faculty of Life Science, Kumamoto University kn-affil= affil-num=8 en-affil=Oral Radiology and Artificial Intelligence, Asahi University kn-affil= affil-num=9 en-affil=JOB CORPORATION kn-affil= affil-num=10 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= en-keyword=Photon-counting detector kn-keyword=Photon-counting detector en-keyword=Pulse pile-up kn-keyword=Pulse pile-up en-keyword=Dead time kn-keyword=Dead time en-keyword=Counting-loss correction kn-keyword=Counting-loss correction en-keyword=Charge-sharing effect kn-keyword=Charge-sharing effect en-keyword=Effective atomic number kn-keyword=Effective atomic number END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250714 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Week 2 remission with vedolizumab as a predictor of long-term remission in patients with ulcerative colitis: a multicenter, retrospective, observational study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims Vedolizumab (VDZ), a gut-selective monoclonal antibody for ulcerative colitis (UC) treatment, has no established biomarkers or clinical features that predict long-term remission. Week 2 remission, a potential predictor of long-term remission, could inform maintenance treatment strategy.
Methods This retrospective, observational chart review included patients with UC in Japan who initiated VDZ between December 2018 and February 2020. Outcome measures included 14- and 54-week remission rates in patients with week 2 and non-week 2 remission (remission by week 14), 54-week remission rates in patients with week 14 remission and primary nonresponse, and predictive factors of week 2 and week 54 remission (logistic regression).
Results Overall, 332 patients with UC (176 biologic-na?ve and 156 biologic-non-na?ve) were included. Significantly more biologic-na?ve than biologic-non-na?ve patients achieved week 2 remission (36.9% vs. 28.2%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.05?1.94; P=0.0224). Week 54 remission rates were significantly different between week 14 remission and primary nonresponse (both groups: P<0.0001), and between week 2 and non-week 2 remission (all patients: OR, 2.41; 95% CI, 1.30?4.48; P=0.0052; biologic-na?ve patients: OR, 2.40; 95% CI, 1.10?5.24; P=0.0280). Week 2 remission predictors were male sex, no anti-tumor necrosis factor alpha exposure, and normal/mild endoscopic findings. Week 54 remission was significantly associated with week 2 remission and no tacrolimus use.
Conclusions Week 2 remission with VDZ is a predictor of week 54 remission in patients with UC. Week 2 may be used as an evaluation point for UC treatment decisions. (Japanese Registry of Clinical Trials: jRCT-1080225363) en-copyright= kn-copyright= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FernandezJovelle L en-aut-sei=Fernandez en-aut-mei=Jovelle L kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=Colitis, ulcerative kn-keyword=Colitis, ulcerative en-keyword=Inflammatory bowel diseases kn-keyword=Inflammatory bowel diseases en-keyword=Japan kn-keyword=Japan en-keyword=Vedolizumab kn-keyword=Vedolizumab END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The duration of prior anti-tumor necrosis factor agents is associated with the effectiveness of vedolizumab in patients with ulcerative colitis: a real-world multicenter retrospective study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims Previous literature suggests that the response of patients with ulcerative colitis to vedolizumab may be affected by previous biologic therapy exposure. This real-world study evaluated vedolizumab treatment effectiveness in biologicnon-na?ve patients.
Methods This was a multicenter, retrospective, observational chart review of records from 16 hospitals in Japan (December 1, 2018, to February 29, 2020). Included patients who had ulcerative colitis, were aged ? 20 years, and received at least 1 dose of vedolizumab. Outcomes included clinical remission rates from weeks 2 to 54 according to prior biologic exposure status and factors associated with clinical remission up to week 54.
Results A total of 370 eligible patients were included. Clinical remission rates were significantly higher in biologic-na?ve (n=197) than in biologic-non-na?ve (n=173) patients for weeks 2 to 54 of vedolizumab treatment. Higher clinical remission rates up to week 54 were significantly associated with lower disease severity (partial Mayo score ? 4, P= 0.001; albumin ? 3.0, P= 0.019) and the duration of prior anti-tumor necrosis factor α (anti-TNFα) therapy (P= 0.026). Patients with anti-TNFα therapy durations of < 3 months, 3 to < 12 months, and ? 12 months had clinical remission rates of 28.1%, 32.7%, and 60.0%, respectively (P= 0.001 across groups).
Conclusions The effectiveness of vedolizumab in biologic-non-na?ve patients was significantly influenced by duration of prior anti-TNFα therapy. (Japanese Registry of Clinical Trials: jRCT-1080225363) en-copyright= kn-copyright= en-aut-name=KobayashiTaku en-aut-sei=Kobayashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisamatsuTadakazu en-aut-sei=Hisamatsu en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotoyaSatoshi en-aut-sei=Motoya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuuraMinoru en-aut-sei=Matsuura en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiiToshimitsu en-aut-sei=Fujii en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunisakiReiko en-aut-sei=Kunisaki en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShibuyaTomoyoshi en-aut-sei=Shibuya en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakeuchiKen en-aut-sei=Takeuchi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YasudaHiroshi en-aut-sei=Yasuda en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoyamaKaoru en-aut-sei=Yokoyama en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakatsuNoritaka en-aut-sei=Takatsu en-aut-mei=Noritaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaemotoAtsuo en-aut-sei=Maemoto en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TaharaToshiyuki en-aut-sei=Tahara en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TominagaKeiichi en-aut-sei=Tominaga en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ShimadaMasaaki en-aut-sei=Shimada en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KunoNobuaki en-aut-sei=Kuno en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=CavaliereMary en-aut-sei=Cavaliere en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IshiguroKaori en-aut-sei=Ishiguro en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FernandezJovelle L en-aut-sei=Fernandez en-aut-mei=Jovelle L kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HibiToshifumi en-aut-sei=Hibi en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=3 en-affil=Inflammatory Bowel Disease Center, Sapporo-Kosei General Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Kyorin University School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Institute of Science Tokyo kn-affil= affil-num=6 en-affil=Inflammatory Bowel Disease Center, Yokohama City University Medical Center kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Juntendo University School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, IBD Center, Tsujinaka Hospital Kashiwanoha kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, St. Marianna University School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Kitasato University School of Medicine kn-affil= affil-num=12 en-affil=Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital kn-affil= affil-num=13 en-affil=Inflammatory Bowel Disease Center, Sapporo Higashi Tokushukai Hospital kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Saiseikai Utsunomiya Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, Dokkyo Medical University kn-affil= affil-num=16 en-affil=Department of Gastroenterology, NHO Nagoya Medical Center kn-affil= affil-num=17 en-affil=Department of Gastroenterology and Medicine, Fukuoka University Hospital kn-affil= affil-num=18 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=19 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=20 en-affil=Japan Medical Office, Takeda Pharmaceutical Company Limited kn-affil= affil-num=21 en-affil=Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital kn-affil= en-keyword=Tumor necrosis factor-alpha kn-keyword=Tumor necrosis factor-alpha en-keyword=Real-world evidence kn-keyword=Real-world evidence en-keyword=Colitis kn-keyword=Colitis en-keyword=ulcerative kn-keyword=ulcerative en-keyword=Vedolizumab kn-keyword=Vedolizumab en-keyword=Sequencing kn-keyword=Sequencing END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Health-related quality of life, work productivity, and persisting challenges in treated ulcerative colitis patients: a Japanese National Health and Wellness Survey en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aims Despite available treatments for ulcerative colitis (UC), unmet needs persist among patients in Japan. This study explored the health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), indirect cost, and unmet needs among treated UC patients in Japan.
Methods This cross-sectional, observational study utilized data from the online 2017, 2019, and 2021 Japan National Health and Wellness Survey. Respondents were aged ? 18 years and had undergone or were on UC treatment (5-aminosalicylic acid, steroids, immunomodulators/immunosuppressants, biologics/Janus kinase inhibitors [JAKi]). Demographic, general health, and clinical characteristics, medication adherence, HRQoL, WPAI, and indirect cost were collected and analyzed.
Results Among 293 treated UC patients, 83.6% were non-biologic/JAKi users, 29.0% had UC ? 15 years, 34.8% had moderate-to-severe disease severity, 55.3% experienced ? 1 persisting UC symptom, and 91.5% reported UC as bothersome to an extent. Patients reported EuroQoL visual analog scale score of 68.1 and ? 35% reported anxiety and depression. Mean work productivity loss was 29.3%, resulting in an annual mean indirect loss of 1.1 million JPY (45.3 thousand USD) per person. Higher WPAI (impairment) was associated with being male, moderate-to-severe disease severity, and low treatment adherence (P<0.05). Biologics/JAKi users had higher work impairment, and IM/IS users had higher activity impairment than 5-aminosalicylic acid users (P<0.05).
Conclusions Despite treatment, Japanese UC patients experienced high disease burden and persistent disease-related challenges. Overall HRQoL were lower than the mean healthy population and work productivity impairment led to high indirect costs. The findings suggest the importance of new interventions for optimizing UC outcomes. en-copyright= kn-copyright= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HuangZhezhou en-aut-sei=Huang en-aut-mei=Zhezhou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=QinFei en-aut-sei=Qin en-aut-mei=Fei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Nathan ArokianathanFatima Megala en-aut-sei=Nathan Arokianathan en-aut-mei=Fatima Megala kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Dav?Kiran en-aut-sei=Dav? en-aut-mei=Kiran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShahShweta en-aut-sei=Shah en-aut-mei=Shweta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimHyunchung en-aut-sei=Kim en-aut-mei=Hyunchung kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Okayama University kn-affil= affil-num=2 en-affil=Cerner Enviza kn-affil= affil-num=3 en-affil=Cerner Enviza kn-affil= affil-num=4 en-affil=Oracle Life Sciences kn-affil= affil-num=5 en-affil=Bristol Myers Squibb kn-affil= affil-num=6 en-affil=Bristol Myers Squibb kn-affil= affil-num=7 en-affil=Bristol Myers Squibb kn-affil= en-keyword=Quality of life kn-keyword=Quality of life en-keyword=Presenteeism kn-keyword=Presenteeism en-keyword=Absenteeism kn-keyword=Absenteeism en-keyword=Ulcerative colitis kn-keyword=Ulcerative colitis en-keyword=Japan kn-keyword=Japan END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=6 article-no= start-page=e00110-25 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mycobacterium tuberculosis bacillus induces pyroptosis in human lung fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously reported that live, but not dead, virulent Mycobacterium tuberculosis (Mtb) H37Rv bacilli induce cell death in human lung fibroblast cell lines, MRC-5, MRC-9, and TIG-1. Here, using two distinct Mtb strains from two different lineages (HN878 lineage 2 and H37Rv lineage 4), we confirmed cell death at day 2 after infection with a device that measures cell growth/cytotoxicity in real time (Maestro-Z [AXION]). Mtb bacilli uptake by the fibroblast was confirmed with a transmission electron microscope on day 2. Expressions of inflammatory cytokines and interleukin (IL)?1β, IL-6, and IL-8 were observed when exposed to live, but not dead bacteria. The cell death of fibroblasts induced by both Mtb strains tested was prevented by caspase-1/4 and NLRP3 inflammasome inhibitors, but not by caspase-3 and caspase-9 inhibitors. Therefore, we classified the fibroblast cell death by Mtb infection as pyroptosis. To investigate the biological and pathological relevance of fibroblast cell death by Mtb infection, we performed dual RNA-Seq analysis on Mtb within fibroblasts and Mtb-infected fibroblasts at day 2. In Mtb bacilli tcrR, secE2, ahpD, and mazF8 genes were highly induced during infection. These genes play roles in survival in a hypoxic environment, production of a calcium-binding protein-inducing cytokine, and regulation of transcription in a toxin-antitoxin system. The gene expressions of IL-1β, IL-6, and IL-8, caspase-4, and NLRP3, but not of caspase-3 and caspase-9, were augmented in Mtb bacilli-infected fibroblasts. Taken together, our study suggests that Mtb bacilli attempt to survive in lung fibroblasts and that pyroptosis of the host fibroblasts activates the immune system against the infection. en-copyright= kn-copyright= en-aut-name=TakiiTakemasa en-aut-sei=Takii en-aut-mei=Takemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaHiroyuki en-aut-sei=Yamada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotozonoChihiro en-aut-sei=Motozono en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiSho en-aut-sei=Yamasaki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TorrellesJordi B. en-aut-sei=Torrelles en-aut-mei=Jordi B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TurnerJoanne en-aut-sei=Turner en-aut-mei=Joanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimishimaAoi en-aut-sei=Kimishima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsamiYukihiro en-aut-sei=Asami en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HidaShigeaki en-aut-sei=Hida en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OnozakiKikuo en-aut-sei=Onozaki en-aut-mei=Kikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=2 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=3 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=4 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=5 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I?CARE) kn-affil= affil-num=6 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I?CARE) kn-affil= affil-num=7 en-affil=Laboratory of Applied Microbial Chemistry, ?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=8 en-affil=Laboratory of Applied Microbial Chemistry, ?mura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=9 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=11 en-affil=Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=12 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= en-keyword=Mycobacterium tuberculosis kn-keyword=Mycobacterium tuberculosis en-keyword=pyroptosis kn-keyword=pyroptosis en-keyword=caspase kn-keyword=caspase en-keyword=RNA-Seq kn-keyword=RNA-Seq en-keyword=cytokine kn-keyword=cytokine en-keyword=fibroblasts kn-keyword=fibroblasts END start-ver=1.4 cd-journal=joma no-vol=90 cd-vols= no-issue=1 article-no= start-page=29 end-page=36 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Elucidation of the phylogenetic relationships among <i>Alpinia</i> species native to the Nansei Islands, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Alpinia species (A. intermedia, A. zerumbet, A. formosana, A. uraiensis, and unidentified strains native to the Daito Islands), which are native to the Nansei Islands, Japan are ornamental plants that can be used as resources to produce seasonings and antibacterial and antiviral substances. Despite the usefulness of these plants, little scientific research has been conducted on their phylogenetic relationships. In this study, their phylogenetic relationships were examined based on genomic and chloroplast DNA polymorphisms, repetitive sequence abundance, and cytogenetic perspectives. The results indicated that A. formosana is most likely the outcome of a hybrid of A. zerumbet and A. intermedia, and the unidentified strains native to the Daito Islands are the outcomes of a hybrid of A. zerumbet and A. uraiensis. Immunostaining with a newly produced anti-centromere-specific histone H3 (CENH3) antibody revealed that the number of chromosomes in these species was 2n=48. en-copyright= kn-copyright= en-aut-name=NagakiKiyotaka en-aut-sei=Nagaki en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NarusakaMari en-aut-sei=Narusaka en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NarusakaYoshihiro en-aut-sei=Narusaka en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Okayama Prefectural Technology Center for Agriculture, Forestry, and Fisheries, Research Institute for Biological Sciences (RIBS) kn-affil= affil-num=3 en-affil=Okayama Prefectural Technology Center for Agriculture, Forestry, and Fisheries, Research Institute for Biological Sciences (RIBS) kn-affil= en-keyword=Alpinia kn-keyword=Alpinia en-keyword=Nansei Islands kn-keyword=Nansei Islands en-keyword=Chromosome number kn-keyword=Chromosome number en-keyword=CENH3 (centromere-specific histone H3) kn-keyword=CENH3 (centromere-specific histone H3) END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=10 article-no= start-page=3332 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Experience of High Tibial Osteotomy for Patients with Rheumatoid Arthritis Treated with Recent Medication: A Case Series en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: High tibial osteotomy (HTO) was generally not indicated in patients with rheumatoid arthritis (RA) because synovial inflammation may exacerbate joint damage postoperatively. Recently, joint destruction in RA has dramatically changed with the introduction of methotrexate (MTX) and biological disease-modifying antirheumatic drugs (bDMARDs). This study aimed to investigate the clinical outcomes of HTO for patients with RA treated with recent medication. Methods: In this study, patients with RA who underwent HTO between 2016 and 2020 were retrospectively reviewed. Patients whose follow-up period was <2 years and those whose onset of RA occurred after HTO were excluded. Clinical outcomes were investigated using the Japanese orthopedic Association (JOA) and visual analog scale (VAS) scores. Results: Seven patients (two males and five females, mean age 72.0 ± 6.2 years, mean body mass index 24.0 ± 2.9 kg/m2) were included in this study. The mean follow-up period was 62.1 ± 21.4 months. Open-wedge and hybrid closed-wedge HTO were performed in two and five cases, respectively. MTX was used for all cases. The bDMARDs were used in six cases (golimumab and tocilizumab in four and two cases, respectively). JOA scores significantly improved from 63.6 ± 10.7 preoperatively to 90.7 ± 5.3 postoperatively (p = 0.0167 Wilcoxon rank test). VAS scores significantly decreased from 48.6 ± 12.2 preoperatively to 11.4 ± 6.9 postoperatively (p = 0.017 Wilcoxon rank test). None of the patients underwent total knee arthroplasty. Conclusions: This study showed seven RA patients who underwent HTO treated with recent medication. The prognosis of RA, including joint destruction, has dramatically improved with induction of MTX and bDMARDs. HTO may be one of effective joint preservation surgeries even for patients with RA. To achieve the favorable outcomes, surgeons should pay attention to timing and indication of surgery. en-copyright= kn-copyright= en-aut-name=TakaharaYasuhiro en-aut-sei=Takahara en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakashimaHirotaka en-aut-sei=Nakashima en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchidaYoichiro en-aut-sei=Uchida en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoHisayoshi en-aut-sei=Kato en-aut-mei=Hisayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItaniSatoru en-aut-sei=Itani en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwasakiYuichi en-aut-sei=Iwasaki en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Nippon Kokan Fukuyama Hospital kn-affil= en-keyword=high tibial osteotomy kn-keyword=high tibial osteotomy en-keyword=rheumatoid arthritis kn-keyword=rheumatoid arthritis en-keyword=methotrexate kn-keyword=methotrexate en-keyword=biologic diseasemodifying antirheumatic drugs kn-keyword=biologic diseasemodifying antirheumatic drugs en-keyword=knee surgery kn-keyword=knee surgery en-keyword=joint preservation kn-keyword=joint preservation END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002112 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Animal dsRNA and ssRNA(?) Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=RNA viruses are ubiquitous in the environment and are important pathogens of humans, animals and plants. In 2024, the International Committee on Taxonomy of Viruses Animal dsRNA and ssRNA(?) Viruses Subcommittee submitted 18 taxonomic proposals for consideration. These proposals expanded the known virosphere by classifying 9 new genera and 88 species for newly detected virus genomes. Of note, newly established species expand the large family of Rhabdoviridae to 580 species. A new species in the family Arenaviridae includes a virus detected in Antarctic fish with a unique split nucleoprotein ORF. Additionally, four new species were established for historically isolated viruses with previously unsequenced genomes. Furthermore, three species were abolished due to incomplete genome sequence information, and one family was moved from being unassigned in the phylum Negarnaviricota into a subphylum and order. Herein, we summarize the 18 ratified taxonomic proposals and the general features of the current taxonomy, thereby supporting public and animal health responses. en-copyright= kn-copyright= en-aut-name=HughesHolly R. en-aut-sei=Hughes en-aut-mei=Holly R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BallingerMatthew J. en-aut-sei=Ballinger en-aut-mei=Matthew J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BaoYiming en-aut-sei=Bao en-aut-mei=Yiming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BejermanNicolas en-aut-sei=Bejerman en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BlasdellKim R. en-aut-sei=Blasdell en-aut-mei=Kim R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BrieseThomas en-aut-sei=Briese en-aut-mei=Thomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BrignoneJulia en-aut-sei=Brignone en-aut-mei=Julia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CarreraJean Paul en-aut-sei=Carrera en-aut-mei=Jean Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=De ConinckLander en-aut-sei=De Coninck en-aut-mei=Lander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=de SouzaWilliam Marciel en-aut-sei=de Souza en-aut-mei=William Marciel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DebatHumberto en-aut-sei=Debat en-aut-mei=Humberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DietzgenRalf G. en-aut-sei=Dietzgen en-aut-mei=Ralf G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=D?rrwaldRalf en-aut-sei=D?rrwald en-aut-mei=Ralf kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ErdinMert en-aut-sei=Erdin en-aut-mei=Mert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FooksAnthony R. en-aut-sei=Fooks en-aut-mei=Anthony R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ForbesKristian M. en-aut-sei=Forbes en-aut-mei=Kristian M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Freitas-Ast?aJuliana en-aut-sei=Freitas-Ast?a en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=GarciaJorge B. en-aut-sei=Garcia en-aut-mei=Jorge B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=GeogheganJemma L. en-aut-sei=Geoghegan en-aut-mei=Jemma L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=GrimwoodRebecca M. en-aut-sei=Grimwood en-aut-mei=Rebecca M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HorieMasayuki en-aut-sei=Horie en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HyndmanTimothy H. en-aut-sei=Hyndman en-aut-mei=Timothy H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=JohneReimar en-aut-sei=Johne en-aut-mei=Reimar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KlenaJohn D. en-aut-sei=Klena en-aut-mei=John D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KooninEugene V. en-aut-sei=Koonin en-aut-mei=Eugene V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KostygovAlexei Y. en-aut-sei=Kostygov en-aut-mei=Alexei Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=LetkoMichael en-aut-sei=Letko en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=LiJun-Min en-aut-sei=Li en-aut-mei=Jun-Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=LiuYiyun en-aut-sei=Liu en-aut-mei=Yiyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=MartinMaria Laura en-aut-sei=Martin en-aut-mei=Maria Laura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=MullNathaniel en-aut-sei=Mull en-aut-mei=Nathaniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NazarYael en-aut-sei=Nazar en-aut-mei=Yael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=NowotnyNorbert en-aut-sei=Nowotny en-aut-mei=Norbert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=NunesM?rcio Roberto Teixeira en-aut-sei=Nunes en-aut-mei=M?rcio Roberto Teixeira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=?klandArnfinn Lodden en-aut-sei=?kland en-aut-mei=Arnfinn Lodden kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=RubbenstrothDennis en-aut-sei=Rubbenstroth en-aut-mei=Dennis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=RussellBrandy J. en-aut-sei=Russell en-aut-mei=Brandy J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=SchottEric en-aut-sei=Schott en-aut-mei=Eric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=SeifertStephanie en-aut-sei=Seifert en-aut-mei=Stephanie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=SenCarina en-aut-sei=Sen en-aut-mei=Carina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=ShedroffElizabeth en-aut-sei=Shedroff en-aut-mei=Elizabeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=SironenTarja en-aut-sei=Sironen en-aut-mei=Tarja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=SmuraTeemu en-aut-sei=Smura en-aut-mei=Teemu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=TavaresCamila Prestes Dos Santos en-aut-sei=Tavares en-aut-mei=Camila Prestes Dos Santos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=TeshRobert B. en-aut-sei=Tesh en-aut-mei=Robert B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=TilstonNatasha L. en-aut-sei=Tilston en-aut-mei=Natasha L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=TordoNo?l en-aut-sei=Tordo en-aut-mei=No?l kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=VasilakisNikos en-aut-sei=Vasilakis en-aut-mei=Nikos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=WalkerPeter J. en-aut-sei=Walker en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=WangFei en-aut-sei=Wang en-aut-mei=Fei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=WhitfieldAnna E. en-aut-sei=Whitfield en-aut-mei=Anna E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=WhitmerShannon L.M. en-aut-sei=Whitmer en-aut-mei=Shannon L.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=WolfYuri I. en-aut-sei=Wolf en-aut-mei=Yuri I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=XiaHan en-aut-sei=Xia en-aut-mei=Han kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=YeGong-Yin en-aut-sei=Ye en-aut-mei=Gong-Yin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=YeZhuangxin en-aut-sei=Ye en-aut-mei=Zhuangxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=YurchenkoVyacheslav en-aut-sei=Yurchenko en-aut-mei=Vyacheslav kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=ZhaoMingli en-aut-sei=Zhao en-aut-mei=Mingli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= affil-num=1 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=2 en-affil=Biological Sciences, Mississippi State University kn-affil= affil-num=3 en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Consejo Nacional de Investigaciones Cient?ficas y T?cnicas (CONICET) and Instituto Nacional de Tecnolog?a Agropecuaria (INTA) kn-affil= affil-num=5 en-affil=CSIRO Health and Biosecurity kn-affil= affil-num=6 en-affil=Center for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia University kn-affil= affil-num=7 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=8 en-affil=Instituto Conmemorativo Gorgas de Estudios de la Salud kn-affil= affil-num=9 en-affil=Division of Clinical and Epidemiological Virology, KU Leuven kn-affil= affil-num=10 en-affil=Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky kn-affil= affil-num=11 en-affil=Instituto Nacional de Tecnolog?a Agropecuaria (INTA) kn-affil= affil-num=12 en-affil=QAAFI, The University of Queensland kn-affil= affil-num=13 en-affil=Robert Koch Institut kn-affil= affil-num=14 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=15 en-affil=Animal and Plant Health Agency (APHA) kn-affil= affil-num=16 en-affil=Department of Biological Sciences, University of Arkansas kn-affil= affil-num=17 en-affil=Embrapa Cassava and Fruits kn-affil= affil-num=18 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=19 en-affil=Department of Microbiology and Immunology, University of Otago kn-affil= affil-num=20 en-affil=Department of Microbiology and Immunology, University of Otago kn-affil= affil-num=21 en-affil=Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University kn-affil= affil-num=22 en-affil=School of Veterinary Medicine, Murdoch University kn-affil= affil-num=23 en-affil=German Federal Institute for Risk Assessment kn-affil= affil-num=24 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=25 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=26 en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health kn-affil= affil-num=27 en-affil=University of Ostrava kn-affil= affil-num=28 en-affil=Institut Pasteur, Universit? Paris Cit?, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=29 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=30 en-affil=Paul G. Allen School for Global Health, Washington State University kn-affil= affil-num=31 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=32 en-affil=National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences kn-affil= affil-num=33 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=34 en-affil=Department of Natural Sciences, Shawnee State University kn-affil= affil-num=35 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=36 en-affil=College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health kn-affil= affil-num=37 en-affil=Universidade Federal do Par? kn-affil= affil-num=38 en-affil=Pharmaq Analytiq kn-affil= affil-num=39 en-affil=Institute of Diagnostic Virology, Friedrich-Loeffler-Institut kn-affil= affil-num=40 en-affil=Centers for Disease Control and Prevention kn-affil= affil-num=41 en-affil=Institute of Marine and Environmental Technology, University of Maryland Center for Environmental Science kn-affil= affil-num=42 en-affil=Paul G. Allen School for Global Health, Washington State University kn-affil= affil-num=43 en-affil=Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS kn-affil= affil-num=44 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=45 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=46 en-affil=Department of Virology, University of Helsinki kn-affil= affil-num=47 en-affil=Integrated Group of Aquaculture and Environmental Studies, Federal University of Paran? kn-affil= affil-num=48 en-affil=Department of Pathology, The University of Texas Medical Branch kn-affil= affil-num=49 en-affil=Department of Microbiology and Immunology, Indiana University School of Medicine kn-affil= affil-num=50 en-affil=Institut Pasteur kn-affil= affil-num=51 en-affil=Department of Pathology, The University of Texas Medical Branch kn-affil= affil-num=52 en-affil=University of Queensland kn-affil= affil-num=53 en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences kn-affil= affil-num=54 en-affil=North Carolina State University kn-affil= affil-num=55 en-affil=Viral Special Pathogens Branch, The Centers for Disease Control and Prevention kn-affil= affil-num=56 en-affil=Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health kn-affil= affil-num=57 en-affil=Wuhan Institute of Virology, Chinese Academy of Sciences kn-affil= affil-num=58 en-affil=Institute of Insect Sciences, Zhejiang University kn-affil= affil-num=59 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=60 en-affil=University of Ostrava kn-affil= affil-num=61 en-affil=Department of Pathobiology and Population Sciences, Royal Veterinary College kn-affil= END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002114 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses from the Plant Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In March 2025, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote, newly proposed taxa were added to those under the mandate of the Plant Viruses Subcommittee. In brief, 1 new order, 3 new families, 6 new genera, 2 new subgenera and 206 new species were created. Some taxa were reorganized. Genus Cytorhabdovirus in the family Rhabdoviridae was abolished and its taxa were redistributed into three new genera Alphacytorhabdovirus, Betacytorhabdovirus and Gammacytorhabdovirus. Genus Waikavirus in the family Secoviridae was reorganized into two subgenera (Actinidivirus and Ritunrivirus). One family and four previously unaffiliated genera were moved to the newly established order Tombendovirales. Twelve species not assigned to a genus were abolished. To comply with the ICTV mandate of a binomial format for virus species, eight species were renamed. Demarcation criteria in the absence of biological information were defined in the genus Ilarvirus (family Bromoviridae). This article presents the updated taxonomy put forth by the Plant Viruses Subcommittee and ratified by the ICTV. en-copyright= kn-copyright= en-aut-name=RubinoLuisa en-aut-sei=Rubino en-aut-mei=Luisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AbrahamianPeter en-aut-sei=Abrahamian en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AnWenxia en-aut-sei=An en-aut-mei=Wenxia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArandaMiguel A. en-aut-sei=Aranda en-aut-mei=Miguel A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Ascencio-Iba?ezJos? T. en-aut-sei=Ascencio-Iba?ez en-aut-mei=Jos? T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BejermanNicolas en-aut-sei=Bejerman en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BlouinArnaud G. en-aut-sei=Blouin en-aut-mei=Arnaud G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CandresseThierry en-aut-sei=Candresse en-aut-mei=Thierry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CantoTomas en-aut-sei=Canto en-aut-mei=Tomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=CaoMengji en-aut-sei=Cao en-aut-mei=Mengji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=CarrJohn P. en-aut-sei=Carr en-aut-mei=John P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ChoWon Kyong en-aut-sei=Cho en-aut-mei=Won Kyong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ConstableFiona en-aut-sei=Constable en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=DasguptaIndranil en-aut-sei=Dasgupta en-aut-mei=Indranil kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=DebatHumberto en-aut-sei=Debat en-aut-mei=Humberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=DietzgenRalf G. en-aut-sei=Dietzgen en-aut-mei=Ralf G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DigiaroMichele en-aut-sei=Digiaro en-aut-mei=Michele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DonaireLivia en-aut-sei=Donaire en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ElbeainoToufic en-aut-sei=Elbeaino en-aut-mei=Toufic kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FargetteDenis en-aut-sei=Fargette en-aut-mei=Denis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=FilardoFiona en-aut-sei=Filardo en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FischerMatthias G. en-aut-sei=Fischer en-aut-mei=Matthias G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FontdevilaNuria en-aut-sei=Fontdevila en-aut-mei=Nuria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FoxAdrian en-aut-sei=Fox en-aut-mei=Adrian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=Freitas-AstuaJuliana en-aut-sei=Freitas-Astua en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FuchsMarc en-aut-sei=Fuchs en-aut-mei=Marc kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=GeeringAndrew D.W. en-aut-sei=Geering en-aut-mei=Andrew D.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=GhafariMahan en-aut-sei=Ghafari en-aut-mei=Mahan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=Hafr?nAnders en-aut-sei=Hafr?n en-aut-mei=Anders kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HammondJohn en-aut-sei=Hammond en-aut-mei=John kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=HammondRosemarie en-aut-sei=Hammond en-aut-mei=Rosemarie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=Hasi?w-JaroszewskaBeata en-aut-sei=Hasi?w-Jaroszewska en-aut-mei=Beata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=HebrardEugenie en-aut-sei=Hebrard en-aut-mei=Eugenie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=Hern?ndezCarmen en-aut-sei=Hern?ndez en-aut-mei=Carmen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=HilyJean-Michel en-aut-sei=Hily en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=HosseiniAhmed en-aut-sei=Hosseini en-aut-mei=Ahmed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=HullRoger en-aut-sei=Hull en-aut-mei=Roger kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=Inoue-NagataAlice K. en-aut-sei=Inoue-Nagata en-aut-mei=Alice K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=JordanRamon en-aut-sei=Jordan en-aut-mei=Ramon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=KreuzeJan F. en-aut-sei=Kreuze en-aut-mei=Jan F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=KubotaKenji en-aut-sei=Kubota en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=LeisnerScott en-aut-sei=Leisner en-aut-mei=Scott kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=LettJean-Michel en-aut-sei=Lett en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=LiChengyu en-aut-sei=Li en-aut-mei=Chengyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=LiFan en-aut-sei=Li en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=LiJun Min en-aut-sei=Li en-aut-mei=Jun Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=L?pez-LambertiniPaola M. en-aut-sei=L?pez-Lambertini en-aut-mei=Paola M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=Lopez-MoyaJuan J. en-aut-sei=Lopez-Moya en-aut-mei=Juan J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=MaclotFrancois en-aut-sei=Maclot en-aut-mei=Francois kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=M?kinenKristiina en-aut-sei=M?kinen en-aut-mei=Kristiina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=MartinDarren en-aut-sei=Martin en-aut-mei=Darren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=MassartSebastien en-aut-sei=Massart en-aut-mei=Sebastien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=MillerW. Allen en-aut-sei=Miller en-aut-mei=W. Allen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=MohammadiMusa en-aut-sei=Mohammadi en-aut-mei=Musa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=MollovDimitre en-aut-sei=Mollov en-aut-mei=Dimitre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=MullerEmmanuelle en-aut-sei=Muller en-aut-mei=Emmanuelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=NagataTatsuya en-aut-sei=Nagata en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=Navas-CastilloJes?s en-aut-sei=Navas-Castillo en-aut-mei=Jes?s kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= en-aut-name=NeriyaYutaro en-aut-sei=Neriya en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=62 ORCID= en-aut-name=Ochoa-CoronaFrancisco M. en-aut-sei=Ochoa-Corona en-aut-mei=Francisco M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=63 ORCID= en-aut-name=OhshimaKazusato en-aut-sei=Ohshima en-aut-mei=Kazusato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=64 ORCID= en-aut-name=Pall?sVicente en-aut-sei=Pall?s en-aut-mei=Vicente kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=65 ORCID= en-aut-name=PappuHanu en-aut-sei=Pappu en-aut-mei=Hanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=66 ORCID= en-aut-name=PetrzikKarel en-aut-sei=Petrzik en-aut-mei=Karel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=67 ORCID= en-aut-name=PoogginMikhail en-aut-sei=Pooggin en-aut-mei=Mikhail kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=68 ORCID= en-aut-name=PrigigalloMaria Isabella en-aut-sei=Prigigallo en-aut-mei=Maria Isabella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=69 ORCID= en-aut-name=Ramos-Gonz?lezPedro L. en-aut-sei=Ramos-Gonz?lez en-aut-mei=Pedro L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=70 ORCID= en-aut-name=RibeiroSimone en-aut-sei=Ribeiro en-aut-mei=Simone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=71 ORCID= en-aut-name=Richert-P?ggelerKatja R. en-aut-sei=Richert-P?ggeler en-aut-mei=Katja R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=72 ORCID= en-aut-name=RoumagnacPhilippe en-aut-sei=Roumagnac en-aut-mei=Philippe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=73 ORCID= en-aut-name=RoyAvijit en-aut-sei=Roy en-aut-mei=Avijit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=74 ORCID= en-aut-name=SabanadzovicSead en-aut-sei=Sabanadzovic en-aut-mei=Sead kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=75 ORCID= en-aut-name=?af??ov?Dana en-aut-sei=?af??ov? en-aut-mei=Dana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=76 ORCID= en-aut-name=SaldarelliPasquale en-aut-sei=Saldarelli en-aut-mei=Pasquale kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=77 ORCID= en-aut-name=Sanfa?onH?l?ne en-aut-sei=Sanfa?on en-aut-mei=H?l?ne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=78 ORCID= en-aut-name=SarmientoCecilia en-aut-sei=Sarmiento en-aut-mei=Cecilia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=79 ORCID= en-aut-name=SasayaTakahide en-aut-sei=Sasaya en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=80 ORCID= en-aut-name=ScheetsKay en-aut-sei=Scheets en-aut-mei=Kay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=81 ORCID= en-aut-name=SchravesandeWillem E.W. en-aut-sei=Schravesande en-aut-mei=Willem E.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=82 ORCID= en-aut-name=SealSusan en-aut-sei=Seal en-aut-mei=Susan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=83 ORCID= en-aut-name=ShimomotoYoshifumi en-aut-sei=Shimomoto en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=84 ORCID= en-aut-name=S?meraMerike en-aut-sei=S?mera en-aut-mei=Merike kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=85 ORCID= en-aut-name=StavoloneLivia en-aut-sei=Stavolone en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=86 ORCID= en-aut-name=StewartLucy R. en-aut-sei=Stewart en-aut-mei=Lucy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=87 ORCID= en-aut-name=TeycheneyPierre-Yves en-aut-sei=Teycheney en-aut-mei=Pierre-Yves kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=88 ORCID= en-aut-name=ThomasJohn E. en-aut-sei=Thomas en-aut-mei=John E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=89 ORCID= en-aut-name=ThompsonJeremy R. en-aut-sei=Thompson en-aut-mei=Jeremy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=90 ORCID= en-aut-name=TiberiniAntonio en-aut-sei=Tiberini en-aut-mei=Antonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=91 ORCID= en-aut-name=TomitakaYasuhiro en-aut-sei=Tomitaka en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=92 ORCID= en-aut-name=TzanetakisIoannis en-aut-sei=Tzanetakis en-aut-mei=Ioannis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=93 ORCID= en-aut-name=UmberMarie en-aut-sei=Umber en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=94 ORCID= en-aut-name=UrbinoCica en-aut-sei=Urbino en-aut-mei=Cica kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=95 ORCID= en-aut-name=van den BurgHarrold A. en-aut-sei=van den Burg en-aut-mei=Harrold A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=96 ORCID= en-aut-name=Van der VlugtRen? A.A. en-aut-sei=Van der Vlugt en-aut-mei=Ren? A.A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=97 ORCID= en-aut-name=VarsaniArvind en-aut-sei=Varsani en-aut-mei=Arvind kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=98 ORCID= en-aut-name=VerhageAdriaan en-aut-sei=Verhage en-aut-mei=Adriaan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=99 ORCID= en-aut-name=VillamorDan en-aut-sei=Villamor en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=100 ORCID= en-aut-name=von BargenSusanne en-aut-sei=von Bargen en-aut-mei=Susanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=101 ORCID= en-aut-name=WalkerPeter J. en-aut-sei=Walker en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=102 ORCID= en-aut-name=WetzelThierry en-aut-sei=Wetzel en-aut-mei=Thierry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=103 ORCID= en-aut-name=WhitfieldAnna E. en-aut-sei=Whitfield en-aut-mei=Anna E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=104 ORCID= en-aut-name=WylieStephen J. en-aut-sei=Wylie en-aut-mei=Stephen J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=105 ORCID= en-aut-name=YangCaixia en-aut-sei=Yang en-aut-mei=Caixia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=106 ORCID= en-aut-name=ZerbiniF. Murilo en-aut-sei=Zerbini en-aut-mei=F. Murilo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=107 ORCID= en-aut-name=ZhangSong en-aut-sei=Zhang en-aut-mei=Song kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=108 ORCID= affil-num=1 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=2 en-affil=USDA-ARS, BARC, National Germplasm Resources Laboratory kn-affil= affil-num=3 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=4 en-affil=Centro de Edafolog?a y Biolog?a Aplicada del Segura-CSIC kn-affil= affil-num=5 en-affil=Department of Molecular and Structural Biochemistry, North Carolina State University kn-affil= affil-num=6 en-affil=Unidad de Fitopatolog?a y Modelizaci?n Agr?cola (UFYMA) INTA-CONICET kn-affil= affil-num=7 en-affil=Plant Protection Department kn-affil= affil-num=8 en-affil=UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE kn-affil= affil-num=9 en-affil=Margarita Salas Center for Biological Research (CIB-CSIC) Spanish Council for Scientific Research (CSIC) kn-affil= affil-num=10 en-affil=National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University kn-affil= affil-num=11 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=12 en-affil=Agriculture and Life Sciences Research Institute, Kangwon National University kn-affil= affil-num=13 en-affil=Agriculture Victoria Research, Department of Energy, Environment and Climate Action and School of Applied Systems Biology, La Trobe University kn-affil= affil-num=14 en-affil=University of Delhi South Campu kn-affil= affil-num=15 en-affil=Unidad de Fitopatolog?a y Modelizaci?n Agr?cola (UFYMA) INTA-CONICET kn-affil= affil-num=16 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=17 en-affil=CIHEAM, Istituto Agronomico Mediterraneo of Bari kn-affil= affil-num=18 en-affil=Centro de Edafolog?a y Biolog?a Aplicada del Segura-CSIC kn-affil= affil-num=19 en-affil=CIHEAM, Istituto Agronomico Mediterraneo of Bari kn-affil= affil-num=20 en-affil=Virus South Data kn-affil= affil-num=21 en-affil=Queensland Department of Primary Industries kn-affil= affil-num=22 en-affil=Max Planck Institute for Marine Microbiology kn-affil= affil-num=23 en-affil=Plant Protection Department kn-affil= affil-num=24 en-affil=Fera Science Ltd (Fera), York Biotech Campus kn-affil= affil-num=25 en-affil=Embrapa Cassava and Fruits, Brazilian Agricultural Research Corporation kn-affil= affil-num=26 en-affil=Plant Pathology, Cornell University kn-affil= affil-num=27 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=28 en-affil=Department of Biology, University of Oxford kn-affil= affil-num=29 en-affil=Swedish University of Agriculture kn-affil= affil-num=30 en-affil=USDA-ARS, USNA, Floral and Nursery Plants Research Unit kn-affil= affil-num=31 en-affil=USDA-ARS, BARC, Molecular Plant Pathology Laboratory kn-affil= affil-num=32 en-affil=Institute of Plant Protection-NRI kn-affil= affil-num=33 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro kn-affil= affil-num=34 en-affil=Instituto de Biolog?a Molecular y Celular de Plantas (IBMCP), Universitat Polit?cnica de Valencia-CSIC kn-affil= affil-num=35 en-affil=Institut Fran?ais de la Vigne et du Vin kn-affil= affil-num=36 en-affil=Vali-e-Asr University of Rafsanjan, Department of Plant Protection kn-affil= affil-num=37 en-affil=Retired from John Innes Centre kn-affil= affil-num=38 en-affil=Embrapa Hortali?as kn-affil= affil-num=39 en-affil=USDA-ARS, USNA, Floral and Nursery Plants Research Unit kn-affil= affil-num=40 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=41 en-affil=International Potato Center (CIP) kn-affil= affil-num=42 en-affil=Institut Pasteur, Universit? Paris Cit?, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=43 en-affil=Institute for Plant Protection, NARO kn-affil= affil-num=44 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=45 en-affil=Department of Biological Sciences, University of Toledo kn-affil= affil-num=46 en-affil=CIRAD, UMR PVBMT kn-affil= affil-num=47 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=48 en-affil=State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University kn-affil= affil-num=49 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=50 en-affil=Instituto de Patolog?a Vegetal (IPAVE), INTA, Unidad de Fitopatolog?a y Modelizaci?n Agr?cola (UFYMA) INTA-CONICET kn-affil= affil-num=51 en-affil=Centre for Research in Agricultural Genomics, CRAG (CSIC-IRTA-UAB-UB) kn-affil= affil-num=52 en-affil=UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE kn-affil= affil-num=53 en-affil=Department of Agricultural Sciences, University of Helsinki kn-affil= affil-num=54 en-affil=Institute of Infectious Disease and Molecular Medicine, University of Cape Town kn-affil= affil-num=55 en-affil=Plant Pathology Laboratory, TERRA Gembloux Agro-Bio Tech, University of Liege kn-affil= affil-num=56 en-affil=Department of Plant Pathology, Entomology and Microbiology, Iowa State University kn-affil= affil-num=57 en-affil=Department of Plant Protection, Gorgan University of Agricultural Sciences and Natural Resources kn-affil= affil-num=58 en-affil=USDA-APHIS, Plant Protection and Quarantine kn-affil= affil-num=59 en-affil=CIRAD, AGAP Institut; AGAP Institut, University of Montpellier; CIRAD, INRAE kn-affil= affil-num=60 en-affil=Instituto de Ci?ncias Biol?gicas, Universidade de Bras?lia kn-affil= affil-num=61 en-affil=Instituto de Hortofruticultura Subtropical y Mediterr?nea “La Mayora” (IHSM-UMA-CSIC), Consejo Superior de Investigaciones Cient?ficas kn-affil= affil-num=62 en-affil=Utsunomiya University kn-affil= affil-num=63 en-affil=Oklahoma State University, Institute for Biosecurity & Microbial Forensics kn-affil= affil-num=64 en-affil=Saga University kn-affil= affil-num=65 en-affil=Instituto de Biolog?a Molecular y Celular de Plantas (IBMCP), Universitat Polit?cnica de Valencia-CSIC kn-affil= affil-num=66 en-affil=Department of Plant Pathology, Washington State University kn-affil= affil-num=67 en-affil=Institute of Plant Molecular Biology kn-affil= affil-num=68 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD kn-affil= affil-num=69 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=70 en-affil=Applied Molecular Biology Laboratory, Instituto Biol?gico de S?o Paulo kn-affil= affil-num=71 en-affil=Embrapa Recursos Gen?ticos e Biotecnologia kn-affil= affil-num=72 en-affil=Julius K?hn Institute, Federal Research Centre for Cultivated Plants, Institute for Epidemiology and Pathogen Diagnostics kn-affil= affil-num=73 en-affil=CIRAD, UMR PHIM kn-affil= affil-num=74 en-affil=USDA-ARS, BARC, Molecular Plant Pathology Laboratory, Beltsville, MD, USA kn-affil= affil-num=75 en-affil=Department of Agricultural Science and Plant Protection, Mississippi State University kn-affil= affil-num=76 en-affil=Department of Cell Biology and Genetics, Faculty of Science, Palack? University Olomouc kn-affil= affil-num=77 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=78 en-affil=Summerland Research and Development Centre, Agriculture and Agri-Food Canada kn-affil= affil-num=79 en-affil=Department of Chemistry and Biotechnology, Tallinn University of Technology kn-affil= affil-num=80 en-affil=Strategic Planning Headquarters, NARO kn-affil= affil-num=81 en-affil=Department of Plant Pathology, Ecology and Evolution, Oklahoma State University kn-affil= affil-num=82 en-affil=Molecular Plant Pathology, University of Amsterdam kn-affil= affil-num=83 en-affil=Natural Resources Institute, University of Greenwich kn-affil= affil-num=84 en-affil=Kochi Agricultural Research Center kn-affil= affil-num=85 en-affil=Department of Chemistry and Biotechnology, Tallinn University of Technology kn-affil= affil-num=86 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=87 en-affil=Currently unaffiliated kn-affil= affil-num=88 en-affil=CIRAD, UMR PVBMT & UMR PVBMT, Universit? de la R?union kn-affil= affil-num=89 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=90 en-affil=Plant Health and Environment Laboratory kn-affil= affil-num=91 en-affil=Council for Agricultural Research and Economics, Research Centre for Plant Protection and Certification kn-affil= affil-num=92 en-affil=Institute for Plant Protection, NARO kn-affil= affil-num=93 en-affil=Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System kn-affil= affil-num=94 en-affil=INRAE, UR ASTRO kn-affil= affil-num=95 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro kn-affil= affil-num=96 en-affil=Molecular Plant Pathology, University of Amsterdam kn-affil= affil-num=97 en-affil=Wageningen University and Research kn-affil= affil-num=98 en-affil=The Biodesign Center for Fundamental and Applied Microbiomics, Center for Evolution and Medicine, School of Life Sciences, Arizona State University kn-affil= affil-num=99 en-affil=Rijk Zwaan Breeding B.V. kn-affil= affil-num=100 en-affil=Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System kn-affil= affil-num=101 en-affil=Humboldt-Universit?t zu Berlin, Thaer-Institute of Agricultural and Horticultural Sciences kn-affil= affil-num=102 en-affil=The University of Queensland kn-affil= affil-num=103 en-affil=Dienstleistungszentrum L?ndlicher Raum Rheinpfalz kn-affil= affil-num=104 en-affil=North Carolina State University kn-affil= affil-num=105 en-affil=Food Futures Institute, Murdoch University kn-affil= affil-num=106 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=107 en-affil=Dep. de Fitopatologia/BIOAGRO, Universidade Federal de Vi?osa kn-affil= affil-num=108 en-affil=National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=9 article-no= start-page=2604 end-page=2611 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240830 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rethinking Thin-Layer Chromatography for Screening Technetium-99m Radiolabeled Polymer Nanoparticles en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thin-layer chromatography (TLC) is commonly employed to screen technetium-99m labeled polymer nanoparticle batches for unreduced pertechnetate and radio-colloidal impurities. Although this method is widely accepted, our findings applying radiolabeled PLGA/PLA?PEG nanoparticles underscore its lack of transferability between different settings and its limitations as a standalone quality control tool. While TLC profiles may appear similar for purified and radiocolloid containing nanoparticle formulations, their in vivo behavior can vary significantly, as demonstrated by discrepancies between TLC results and single-photon emission computed tomography (SPECT) and biodistribution data. This highlights the urgent need for a case-by-case evaluation of TLC methods for each specific nanoparticle type. Our study revealed that polymeric nanoparticles cannot be considered analytically uniform entities in the context of TLC analysis, emphasizing the complex interplay between nanoparticle composition, radiolabeling conditions, and subsequent biological behavior. en-copyright= kn-copyright= en-aut-name=SchorrKathrin en-aut-sei=Schorr en-aut-mei=Kathrin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChenXinyu en-aut-sei=Chen en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Arias-LozaAnahi Paula en-aut-sei=Arias-Loza en-aut-mei=Anahi Paula kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LangJohannes en-aut-sei=Lang en-aut-mei=Johannes kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HiguchiTakahiro en-aut-sei=Higuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GoepferichAchim en-aut-sei=Goepferich en-aut-mei=Achim kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pharmaceutical Technology, University of Regensburg kn-affil= affil-num=2 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=3 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital W?rzburg kn-affil= affil-num=5 en-affil=Department of Pharmaceutical Technology, University of Regensburg kn-affil= affil-num=6 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pharmaceutical Technology, University of Regensburg kn-affil= en-keyword=polymer nanoparticles kn-keyword=polymer nanoparticles en-keyword=direct 99mTc-labeling kn-keyword=direct 99mTc-labeling en-keyword=single-photon emission computed tomography kn-keyword=single-photon emission computed tomography en-keyword=radio-thin layer chromatography kn-keyword=radio-thin layer chromatography en-keyword=radiocolloids kn-keyword=radiocolloids END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=6 article-no= start-page=466 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Artificial Intelligence Approach in Machine Learning-Based Modeling and Networking of the Coronavirus Pathogenesis Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=The coronavirus pathogenesis pathway, which consists of severe acute respiratory syndrome (SARS) coronavirus infection and signaling pathways, including the interferon pathway, the transforming growth factor beta pathway, the mitogen-activated protein kinase pathway, the apoptosis pathway, and the inflammation pathway, is activated upon coronaviral infection. An artificial intelligence approach based on machine learning was utilized to develop models with images of the coronavirus pathogenesis pathway to predict the activation states. Data on coronaviral infection held in a database were analyzed with Ingenuity Pathway Analysis (IPA), a network pathway analysis tool. Data related to SARS coronavirus 2 (SARS-CoV-2) were extracted from more than 100,000 analyses and datasets in the IPA database. A total of 27 analyses, including nine analyses of SARS-CoV-2-infected human-induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes and fibroblasts, and a total of 22 analyses of SARS-CoV-2-infected lung adenocarcinoma (LUAD), were identified as being related to “human” and “SARS coronavirus 2” in the database. The coronavirus pathogenesis pathway was activated in SARS-CoV-2-infected iPSC-derived cells and LUAD cells. A prediction model was developed in Python 3.11 using images of the coronavirus pathogenesis pathway under different conditions. The prediction model of activation states of the coronavirus pathogenesis pathway may aid in treatment identification. en-copyright= kn-copyright= en-aut-name=TanabeShihori en-aut-sei=Tanabe en-aut-mei=Shihori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=QuaderSabina en-aut-sei=Quader en-aut-mei=Sabina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoRyuichi en-aut-sei=Ono en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoAkihisa en-aut-sei=Yamamoto en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaMotohiro en-aut-sei=Kojima en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PerkinsEdward J. en-aut-sei=Perkins en-aut-mei=Edward J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion kn-affil= affil-num=3 en-affil=Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Mechanical Systems Engineering, Graduate School of Systems Design Tokyo Metropolitan University kn-affil= affil-num=6 en-affil=Department of Surgical Pathology, Kyoto Prefecture University of Medicine kn-affil= affil-num=7 en-affil=US Army Engineer Research and Development Center kn-affil= affil-num=8 en-affil=Department of Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=coronavirus kn-keyword=coronavirus en-keyword=coronaviral infection kn-keyword=coronaviral infection en-keyword=machine learning kn-keyword=machine learning en-keyword=pathway analysis kn-keyword=pathway analysis en-keyword=predictionmodel kn-keyword=predictionmodel en-keyword=molecular network kn-keyword=molecular network en-keyword=molecular pathway image kn-keyword=molecular pathway image en-keyword=network analysis kn-keyword=network analysis END start-ver=1.4 cd-journal=joma no-vol=104 cd-vols= no-issue=3 article-no= start-page=104810 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An ultra-simplified protocol for PCR template preparation from both unsporulated and sporulated Eimeria oocysts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Molecular biological techniques have enabled the accurate identification of the avian Eimeria parasite, however, the preparation of PCR template remains a bottleneck due to contaminants from feces and the robust oocyst's wall resistant to chemical and mechanical force. Generally, the preparation of PCR template involves three main steps: (1) pretreatment of oocysts; (2) disruption of oocysts; and (3) purification of genomic DNA. We prepared PCR templates from both unsporulated and sporulated E. tenella oocysts using various protocols, followed by species-specific PCR to define the limit of detection. Our data revealed that whereas neither pretreatment of oocysts with sodium hypochlorite nor purification of genomic DNA with commercial kits improved the limit of detection of PCR, disruption of oocysts was a critical step in the preparation of PCR templates. The most sensitive PCR assay was achieved with the template prepared by disrupting oocysts suspended in distilled water, followed by bead-beating and heating at 99°C for 5 min, which detected 0.16 oocysts per PCR. This ultra-simplified protocol for preparation of PCR template, which does not require expensive reagents or equipment, will significantly enhance the sensitive and efficient molecular identification of Eimeria. It will improve our understanding of the prevalence of this parasite at the species level and contribute to the development of techniques for the control in the field. en-copyright= kn-copyright= en-aut-name=TakanoAruto en-aut-sei=Takano en-aut-mei=Aruto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UmaliDennis V. en-aut-sei=Umali en-aut-mei=Dennis V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WardhanaApril H. en-aut-sei=Wardhana en-aut-mei=April H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SawitriDyah H. en-aut-sei=Sawitri en-aut-mei=Dyah H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TeramotoIsao en-aut-sei=Teramoto en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HatabuToshimitsu en-aut-sei=Hatabu en-aut-mei=Toshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KidoYasutoshi en-aut-sei=Kido en-aut-mei=Yasutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanekoAkira en-aut-sei=Kaneko en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SasaiKazumi en-aut-sei=Sasai en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatohHiromitsu en-aut-sei=Katoh en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsubayashiMakoto en-aut-sei=Matsubayashi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Departments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan University kn-affil= affil-num=2 en-affil=Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of the Philippines Los Ba?os, College kn-affil= affil-num=3 en-affil=Research Center for Veterinary Science, National Research and Innovation Agency kn-affil= affil-num=4 en-affil=Research Center for Veterinary Science, National Research and Innovation Agency kn-affil= affil-num=5 en-affil=Departments of Virology and Parasitology, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=6 en-affil=Laboratory of Animal Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Departments of Virology and Parasitology, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=8 en-affil=Departments of Virology and Parasitology, Graduate School of Medicine, Osaka Metropolitan University kn-affil= affil-num=9 en-affil=Departments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan University kn-affil= affil-num=10 en-affil=Departments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan University kn-affil= affil-num=11 en-affil=Departments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan University kn-affil= en-keyword=Coccidian parasite kn-keyword=Coccidian parasite en-keyword=Eimeria tenella kn-keyword=Eimeria tenella en-keyword=Extraction kn-keyword=Extraction en-keyword=Molecular identification kn-keyword=Molecular identification en-keyword=Oocyst kn-keyword=Oocyst END start-ver=1.4 cd-journal=joma no-vol=351 cd-vols= no-issue= article-no= start-page=199522 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evidence for the replication of a plant rhabdovirus in its arthropod mite vector en-subtitle= kn-subtitle= en-abstract= kn-abstract=Transmission of plant viruses that replicate in the insect vector is known as persistent-propagative manner. However, it remains unclear whether such virus-vector relationships also occur between plant viruses and other biological vectors such as arthropod mites. In this study, we investigated the possible replication of orchid fleck virus (OFV), a segmented plant rhabdovirus, within its mite vector (Brevipalpus californicus s.l.) using quantitative RT-qPCR, western blotting and next-generation sequencing. Time-course RT-qPCR and western blot analyses showed an increasing OFV accumulation pattern in mites after virus acquisition. Since OFV genome expression requires the transcription of polyadenylated mRNAs, polyadenylated RNA fractions extracted from the viruliferous mite samples and OFV-infected plant leaves were used for RNA-seq analysis. In the mite and plant datasets, a large number of sequence reads were aligned to genomic regions of OFV RNA1 and RNA2 corresponding to transcribed viral gene mRNAs. This includes the short polyadenylated transcripts originating from the leader and trailer regions at the ends of the viral genome, which are believed to play a crucial role in viral transcription/replication. In contrast, a low number of reads were mapped to the non-transcribed regions (gene junctions). These results strongly suggested that OFV gene expression occurs both in mites and plants. Additionally, deep sequencing revealed the accumulation of OFV-derived small RNAs in mites, although their size profiles differ from those found in plants. Taken together, our results indicated that OFV replicates within a mite vector and is targeted by the RNA-silencing mechanism. en-copyright= kn-copyright= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujitaMiki 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=TelengechPaul en-aut-sei=Telengech en-aut-mei=Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruyamKazuyuki en-aut-sei=Maruyam en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HyodoKiwamu en-aut-sei=Hyodo en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TassiAline Daniele en-aut-sei=Tassi en-aut-mei=Aline Daniele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OchoaRonald en-aut-sei=Ochoa en-aut-mei=Ronald kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AndikaIda Bagus en-aut-sei=Andika en-aut-mei=Ida Bagus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=Institute of Plant Science and Resources (IPSR), Okayama 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=Tropical Research and Education Center, University of Florida kn-affil= affil-num=7 en-affil=Systematic Entomology Laboratory, USDA kn-affil= affil-num=8 en-affil=College of Plant Protection, Northwest A&F University kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=Rhabdovirus kn-keyword=Rhabdovirus en-keyword=Plant kn-keyword=Plant en-keyword=Mite kn-keyword=Mite en-keyword=Vector kn-keyword=Vector en-keyword=Replication kn-keyword=Replication en-keyword=mRNA kn-keyword=mRNA en-keyword=Small RNA kn-keyword=Small RNA END start-ver=1.4 cd-journal=joma no-vol=121 cd-vols= no-issue=5 article-no= start-page=e70046 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spider mite tetranins elicit different defense responses in different host habitats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Spider mites (Tetranychus urticae) are a major threat to economically important crops. Here, we investigated the potential of tetranins, in particular Tet3 and Tet4, as T. urticae protein-type elicitors that stimulate plant defense. Truncated Tet3 and Tet4 proteins showed efficacy in activating the defense gene pathogenesis-related 1 (PR1) and inducing phytohormone production in leaves of Phaseolus vulgaris. In particular, Tet3 caused a drastically higher Ca2+ influx in leaves, but a lower reactive oxygen species (ROS) generation compared to other tetranins, whereas Tet4 caused a low Ca2+ influx and a high ROS generation in the host plants. Such specific and non-specific elicitor activities were examined by knockdown of Tet3 and Tet4 expressions in mites, confirming their respective activities and in particular showing that they function additively or synergistically to induce defense responses. Of great interest is the fact that Tet3 and Tet4 expression levels were higher in mites on their preferred host, P. vulgaris, compared to the levels in mites on the less-preferred host, Cucumis sativus, whereas Tet1 and Tet2 were constitutively expressed regardless of their host. Furthermore, mites that had been hosted on C. sativus induced lower levels of PR1 expression, Ca2+ influx and ROS generation, i.e., Tet3- and Tet4-responsive defense responses, in both P. vulgaris and C. sativus leaves compared to the levels induced by mites that had been hosted on P. vulgaris. Taken together, these findings show that selected tetranins respond to variable host cues that may optimize herbivore fitness by altering the anti-mite response of the host plant. en-copyright= kn-copyright= en-aut-name=EndoYukiko en-aut-sei=Endo en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaMiku en-aut-sei=Tanaka en-aut-mei=Miku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UemuraTakuya en-aut-sei=Uemura en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanimuraKaori en-aut-sei=Tanimura en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DesakiYoshitake en-aut-sei=Desaki en-aut-mei=Yoshitake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzawaRika en-aut-sei=Ozawa en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BonzanoSara en-aut-sei=Bonzano en-aut-mei=Sara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaffeiMassimo E. en-aut-sei=Maffei en-aut-mei=Massimo E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShinyaTomonori en-aut-sei=Shinya en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GalisIvan en-aut-sei=Galis en-aut-mei=Ivan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ArimuraGen‐ichiro en-aut-sei=Arimura en-aut-mei=Gen‐ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=2 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=3 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=4 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=5 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=6 en-affil=Center for Ecological Research, Kyoto University kn-affil= affil-num=7 en-affil=Department of Life Sciences and Systems Biology, Plant Physiology Unit, University of Turin kn-affil= affil-num=8 en-affil=Department of Life Sciences and Systems Biology, Plant Physiology Unit, University of Turin kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=11 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= en-keyword=Cucumis sativus kn-keyword=Cucumis sativus en-keyword=elicitor kn-keyword=elicitor en-keyword=Phaseolus vulgaris kn-keyword=Phaseolus vulgaris en-keyword=spider mite (Tetranychus urticae) kn-keyword=spider mite (Tetranychus urticae) en-keyword=tetranin kn-keyword=tetranin END start-ver=1.4 cd-journal=joma no-vol=637 cd-vols= no-issue=8046 article-no= start-page=744 end-page=748 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Centrophilic retrotransposon integration via CENH3 chromatin in Arabidopsis en-subtitle= kn-subtitle= en-abstract= kn-abstract=In organisms ranging from vertebrates to plants, major components of centromeres are rapidly evolving repeat sequences, such as tandem repeats (TRs) and transposable elements (TEs), which harbour centromere-specific histone H3 (CENH3)1,2. Complete centromere structures recently determined in human and Arabidopsis suggest frequent integration and purging of retrotransposons within the TR regions of centromeres3,4,5. Despite the high impact of ‘centrophilic’ retrotransposons on the paradox of rapid centromere evolution, the mechanisms involved in centromere targeting remain poorly understood in any organism. Here we show that both Ty3 and Ty1 long terminal repeat retrotransposons rapidly turnover within the centromeric TRs of Arabidopsis species. We demonstrate that the Ty1/Copia element Tal1 (Transposon of Arabidopsis lyrata 1) integrates de novo into regions occupied by CENH3 in Arabidopsis thaliana, and that ectopic expansion of the CENH3 region results in spread of Tal1 integration regions. The integration spectra of chimeric TEs reveal the key structural variations responsible for contrasting chromatin-targeting specificities to centromeres versus gene-rich regions, which have recurrently converted during the evolution of these TEs. Our findings show the impact of centromeric chromatin on TE-mediated rapid centromere evolution, with relevance across eukaryotic genomes. en-copyright= kn-copyright= en-aut-name=TsukaharaSayuri en-aut-sei=Tsukahara en-aut-mei=Sayuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BousiosAlexandros en-aut-sei=Bousios en-aut-mei=Alexandros kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Perez-RomanEstela en-aut-sei=Perez-Roman en-aut-mei=Estela kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamaguchiSota en-aut-sei=Yamaguchi en-aut-mei=Sota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LeduqueBasile en-aut-sei=Leduque en-aut-mei=Basile kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoAimi en-aut-sei=Nakano en-aut-mei=Aimi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NaishMatthew en-aut-sei=Naish en-aut-mei=Matthew kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OsakabeAkihisa en-aut-sei=Osakabe en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToyodaAtsushi en-aut-sei=Toyoda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoHidetaka en-aut-sei=Ito en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EderaAlejandro en-aut-sei=Edera en-aut-mei=Alejandro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TominagaSayaka en-aut-sei=Tominaga en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Juliarni en-aut-sei=Juliarni en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KatoKae en-aut-sei=Kato en-aut-mei=Kae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OdaShoko en-aut-sei=Oda en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InagakiSoichi en-aut-sei=Inagaki en-aut-mei=Soichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Lorkovi?Zdravko en-aut-sei=Lorkovi? en-aut-mei=Zdravko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NagakiKiyotaka en-aut-sei=Nagaki en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=BergerFr?d?ric en-aut-sei=Berger en-aut-mei=Fr?d?ric kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KawabeAkira en-aut-sei=Kawabe en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=QuadranaLeandro en-aut-sei=Quadrana en-aut-mei=Leandro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=HendersonIan en-aut-sei=Henderson en-aut-mei=Ian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KakutaniTetsuji en-aut-sei=Kakutani en-aut-mei=Tetsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=2 en-affil=School of Life Sciences, University of Sussex kn-affil= affil-num=3 en-affil=School of Life Sciences, University of Sussex kn-affil= affil-num=4 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=5 en-affil=Institute of Plant Sciences Paris‐Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Universit? Evry, Universit? Paris kn-affil= affil-num=6 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=8 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=9 en-affil=Center for Genetic Resource Information, National Institute of Genetics kn-affil= affil-num=10 en-affil=Faculty of Science, Hokkaido University kn-affil= affil-num=11 en-affil=Institute of Plant Sciences Paris‐Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Universit? Evry, Universit? Paris kn-affil= affil-num=12 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=13 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Integrated Genetics, National Institute of Genetics kn-affil= affil-num=15 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=16 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= affil-num=17 en-affil=Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC) kn-affil= affil-num=18 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=19 en-affil=Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC) kn-affil= affil-num=20 en-affil=Faculty of Life Sciences, Kyoto Sangyo University kn-affil= affil-num=21 en-affil=Institute of Plant Sciences Paris‐Saclay (IPS2), Centre National de la Recherche Scientifique, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Universit? Evry, Universit? Paris kn-affil= affil-num=22 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=23 en-affil=Department of Biological Sciences, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=262 cd-vols= no-issue=2 article-no= start-page=385 end-page=395 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Analysis of the effect of permeant solutes on the hydraulic resistance of the plasma membrane in cells of Chara corallina en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the cells of Chara corallina, permeant monohydric alcohols including methanol, ethanol and 1-propanol increased the hydraulic resistance of the membrane (Lpm?1). We found that the relative value of the hydraulic resistance (rLpm?1) was linearly dependent on the concentration (Cs) of the alcohol. The relationship is expressed in the equation: rLpm?1?=?ρmCs?+?1, where ρm is the hydraulic resistance modifier coefficient of the membrane. Ye et al. (2004) showed that membrane-permeant glycol ethers also increased Lp?1. We used their data to estimate Lpm?1 and rLpm?1. The values of rLpm?1 fit the above relation we found for alcohols. When we plotted the ρm values of all the permeant alcohols and glycol ethers against their molecular weights (MW), we obtained a linear curve with a slope of 0.014 M?1/MW and with a correlation coefficient of 0.99. We analyzed the influence of the permeant solutes on the relative hydraulic resistance of the membrane (rLpm?1) as a function of the external (π0) and internal (πi) osmotic pressures. The analysis showed that the hydraulic resistance modifier coefficients (ρm) were linearly related to the MW of the permeant solutes with a slope of 0.012 M?1/MW and with a correlation coefficient of 0.84. The linear relationship between the effects of permeating solutes on the hydraulic resistance modifier coefficient (ρm) and the MW can be explained in terms of the effect of the effective osmotic pressure on the hydraulic conductivity of water channels. The result of the analysis suggests that the osmotic pressure and not the size of the permeant solute as proposed by (Ye et al., J Exp Bot 55:449?461, 2004) is the decisive factor in a solute’s influence on hydraulic conductivity. Thus, characean water channels (aquaporins) respond to permeant solutes with essentially the same mechanism as to impermeant solutes. en-copyright= kn-copyright= en-aut-name=TazawaMasashi en-aut-sei=Tazawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WayneRandy en-aut-sei=Wayne en-aut-mei=Randy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Yoshida Biological Laboratory kn-affil= affil-num=2 en-affil=Laboratory of Natural Philosophy, Plant Biology Section, Cornell University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=Chara corallina kn-keyword=Chara corallina en-keyword=Effective osmotic pressure kn-keyword=Effective osmotic pressure en-keyword=Hydraulic resistance kn-keyword=Hydraulic resistance en-keyword=Plasma membrane kn-keyword=Plasma membrane en-keyword=Reflection coefficient kn-keyword=Reflection coefficient END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=10819 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster en-subtitle= kn-subtitle= en-abstract= kn-abstract=Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a high-protein diet (HPD), is vital for suppressing overconsumption of protein. Gut-derived CCHa1 is received by a small subset of enteric neurons that produce short neuropeptide F, thereby modulating protein-specific satiety. Importantly, impairment of the CCHa1-mediated gut-enteric neuronal axis results in ammonia accumulation and a shortened lifespan under HPD conditions. Collectively, our findings unravel the crosstalk of gut hormone and neuronal pathways that orchestrate physiological responses to prevent and adapt to dietary protein overload. en-copyright= kn-copyright= en-aut-name=YoshinariYuto en-aut-sei=Yoshinari en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraTakashi en-aut-sei=Nishimura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoShu en-aut-sei=Kondo en-aut-mei=Shu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanimotoHiromu en-aut-sei=Tanimoto en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiTomoe en-aut-sei=Kobayashi en-aut-mei=Tomoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuyamaMakoto en-aut-sei=Matsuyama en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NiwaRyusuke en-aut-sei=Niwa en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= affil-num=2 en-affil=Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=5 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=6 en-affil=Division of Molecular Genetics, Shigei Medical Research Institute kn-affil= affil-num=7 en-affil=Division of Molecular Genetics, Shigei Medical Research Institute kn-affil= affil-num=8 en-affil=Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neurotransmitter and Receptor Mapping in Drosophila Circadian Clock Neurons via T2A-GAL4 Screening en-subtitle= kn-subtitle= en-abstract= kn-abstract=The circadian neuronal network in the brain comprises central pacemaker neurons and associated input and output pathways. These components work together to generate coherent rhythmicity, synchronize with environmental time cues, and convey circadian information to downstream neurons that regulate behaviors such as the sleep/wake cycle. To mediate these functions, neurotransmitters and neuromodulators play essential roles in transmitting and modulating signals between neurons. In Drosophila melanogaster, approximately 240 brain neurons function as clock neurons. Previous studies have identified several neurotransmitters and neuromodulators, including the Pigment-dispersing factor (PDF) neuropeptide, along with their corresponding receptors in clock neurons. However, our understanding of the neurotransmitters and receptors involved in the circadian system remains incomplete. In this study, we conducted a T2A-GAL4-based screening for neurotransmitter and receptor genes expressed in clock neurons. We identified 2 neurotransmitter-related genes and 22 receptor genes. Notably, while previous studies had reported the expression of 6 neuropeptide receptor genes in large ventrolateral neurons (l-LNv), we also found that 14 receptor genes?including those for dopamine, serotonin, and γ-aminobutyric acid?are expressed in l-LNv neurons. These findings suggest that l-LNv neurons serve as key integrative hubs within the circadian network, receiving diverse external signals. en-copyright= kn-copyright= en-aut-name=FukudaAyumi en-aut-sei=Fukuda en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaitoAika en-aut-sei=Saito en-aut-mei=Aika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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 Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=clock neurons kn-keyword=clock neurons en-keyword=neurotransmitter kn-keyword=neurotransmitter en-keyword=T2A-GAL4 kn-keyword=T2A-GAL4 en-keyword=immunostaining kn-keyword=immunostaining en-keyword=Drosophila kn-keyword=Drosophila END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=4 article-no= start-page=329 end-page=334 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficient single-channel current measurements of the human BK channel using a liposome-immobilized gold probe en-subtitle= kn-subtitle= en-abstract= kn-abstract=The human BK channel (hBK) is an essential membrane protein that regulates various biological functions, and its dysfunction leads to serious diseases. Understanding the biophysical properties of hBK channels is crucial for drug development. Artificial lipid bilayer recording is used to measure biophysical properties at the single-channel level. However, this technique is time-consuming and complicated; thus, its measurement efficiency is very low. Previously, we developed a novel technique to improve the measurement efficiency by rapidly forming lipid bilayer membranes and incorporating ion channels into the membrane using a hydrophilically modified gold probe. To further improve our technique for application to the hBK channel, we combined it using the gold probe with a liposome fusion method. Using a probe on which liposomes containing hBK channels were immobilized, the channels were efficiently incorporated into the lipid bilayer membrane, and the measured channel currents showed the current characteristics of the hBK channel. This technique will be useful for the efficient measurements of the channel properties of hBK and other biologically important channels. en-copyright= kn-copyright= en-aut-name=HiranoMinako en-aut-sei=Hirano en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsakuraMami en-aut-sei=Asakura en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IdeToru en-aut-sei=Ide en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Human BK channel kn-keyword=Human BK channel en-keyword=Artificial lipid bilayer recording kn-keyword=Artificial lipid bilayer recording en-keyword=Ion channel current kn-keyword=Ion channel current en-keyword=Single-channel recording kn-keyword=Single-channel recording END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=4 article-no= start-page=510 end-page=524 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250626 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=C1orf50 Drives Malignant Melanoma Progression Through the Regulation of Stemness en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Recent advancements in omics analysis have significantly enhanced our understanding of the molecular pathology of malignant melanoma, leading to the development of novel therapeutic strategies that target specific vulnerabilities within the disease. Despite these improvements, the factors contributing to the poor prognosis of patients with malignant melanoma remain incompletely understood. The aim of this study was to investigate the role of C1orf50 (Chromosome 1 open reading frame 50), a gene previously of unknown function, as a prognostic biomarker in melanoma.
Materials and Methods: We performed comprehensive transcriptome data analysis and subsequent functional validation of the human Skin Cutaneous Melanoma project from The Cancer Genome Atlas (TCGA).
Results: Elevated expression levels of C1orf50 correlated with worse survival outcomes. Mechanistically, we revealed that C1orf50 plays a significant role in the regulation of cell cycle processes and cancer cell stemness, providing a potential avenue for novel therapeutic interventions in melanoma.
Conclusion: This study is the first to identify C1orf50 as a prognostic biomarker in melanoma. The clinical relevance of our results sheds light on the importance of further investigation into the biological mechanisms underpinning C1orf50’s impact on melanoma progression and patient prognosis. en-copyright= kn-copyright= en-aut-name=OTANIYUSUKE en-aut-sei=OTANI en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MAEKAWAMASAKI en-aut-sei=MAEKAWA en-aut-mei=MASAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TANAKAATSUSHI en-aut-sei=TANAKA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PE?ATIRSO en-aut-sei=PE?A en-aut-mei=TIRSO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CHINVANESSA D. en-aut-sei=CHIN en-aut-mei=VANESSA D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ROGACHEVSKAYAANNA en-aut-sei=ROGACHEVSKAYA en-aut-mei=ANNA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=ROEHRLMICHAEL H. en-aut-sei=ROEHRL en-aut-mei=MICHAEL H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FUJIMURAATSUSHI en-aut-sei=FUJIMURA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=2 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=3 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=5 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=6 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=9 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=melanoma kn-keyword=melanoma en-keyword=cancer stem cells kn-keyword=cancer stem cells en-keyword=YAP/TAZ kn-keyword=YAP/TAZ END start-ver=1.4 cd-journal=joma no-vol=301 cd-vols= no-issue=7 article-no= start-page=110291 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A repertoire of visible light?sensitive opsins in the deep-sea hydrothermal vent shrimp Rimicaris hybisae en-subtitle= kn-subtitle= en-abstract= kn-abstract=Unlike terrestrial environments, where humans reside, there is no sunlight in the deep sea. Instead, dim visible light from black-body radiation and bioluminescence illuminates hydrothermal vent areas in the deep sea. A deep-sea hydrothermal vent shrimp, Rimicaris hybisae, is thought to detect this dim light using its enlarged dorsal eye; however, the molecular basis of its photoreception remains unexplored. Here, we characterized the molecular properties of opsins, universal photoreceptive proteins in animals, found in R. hybisae. Transcriptomic analysis identified six opsins: three Gq-coupled opsins, one Opn3, one Opn5, and one peropsin. Functional analysis revealed that five of these opsins exhibited light-dependent G protein activity, whereas peropsin exhibited the ability to convert all-trans-retinal to 11-cis-retinal like photoisomerases. Notably, all the R. hybisae opsins, including Opn5, convergently show visible light sensitivity (around 457?517 nm), whereas most opsins categorized as Opn5 have been demonstrated to be UV sensitive. Mutational analysis revealed that the unique visible light sensitivity of R. hybisae Opn5 is achieved through the stabilization of a protonated Schiff base by a counterion residue at position 83 (Asp83), which differs from the position identified in other opsins. These findings suggest that the vent shrimp R. hybisae has adapted its photoreceptive devices to dim deep-sea hydrothermal light by selectively maintaining a repertoire of visible light?sensitive opsins, including the uniquely tuned Opn5. en-copyright= kn-copyright= en-aut-name=NagataYuya en-aut-sei=Nagata en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyamotoNorio en-aut-sei=Miyamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoKeita en-aut-sei=Sato en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraYosuke en-aut-sei=Nishimura en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniokaYuki en-aut-sei=Tanioka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamanakaYuji en-aut-sei=Yamanaka en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=TakahashiKuto en-aut-sei=Takahashi en-aut-mei=Kuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ObayashiKohei en-aut-sei=Obayashi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsukamotoHisao en-aut-sei=Tsukamoto en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakaiKen en-aut-sei=Takai en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamashitaTakahiro en-aut-sei=Yamashita en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Institute for Extra-Cutting-Edge Science and Technology Avant-Garde Research (X-Star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC) kn-affil= affil-num=3 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Research Center for Bioscience and Nanoscience (CeBN), Research Institute for Marine Resources Utilization, Japan Agency for Marine-Earth Science and Technology (JAMSTEC) kn-affil= affil-num=5 en-affil=School of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=School of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=8 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Biology, Graduate School of Science, Kobe University kn-affil= affil-num=10 en-affil=Department of Biology, Graduate School of Science, Kobe University kn-affil= affil-num=11 en-affil=Institute for Extra-Cutting-Edge Science and Technology Avant-Garde Research (X-Star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC) kn-affil= affil-num=12 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Biophysics, Graduate School of Science, Kyoto University kn-affil= affil-num=14 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=rhodopsin kn-keyword=rhodopsin en-keyword=opsin kn-keyword=opsin en-keyword=G protein?coupled receptor kn-keyword=G protein?coupled receptor en-keyword=signal transduction kn-keyword=signal transduction en-keyword=photoreceptor kn-keyword=photoreceptor en-keyword=vision kn-keyword=vision en-keyword=photobiology kn-keyword=photobiology en-keyword=vent shrimp kn-keyword=vent shrimp en-keyword=deep sea kn-keyword=deep sea en-keyword=molecular evolution kn-keyword=molecular evolution END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=7 article-no= start-page=1152 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240717 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Metatranscriptomic Sequencing of Sheath Blight-Associated Isolates of Rhizoctonia solani Revealed Multi-Infection by Diverse Groups of RNA Viruses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rice sheath blight, caused by the soil-borne fungus Rhizoctonia solani (teleomorph: Thanatephorus cucumeris, Basidiomycota), is one of the most devastating phytopathogenic fungal diseases and causes yield loss. Here, we report on a very high prevalence (100%) of potential virus-associated double-stranded RNA (dsRNA) elements for a collection of 39 fungal strains of R. solani from the rice sheath blight samples from at least four major rice-growing areas in the Philippines and a reference isolate from the International Rice Research Institute, showing different colony phenotypes. Their dsRNA profiles suggested the presence of multiple viral infections among these Philippine R. solani populations. Using next-generation sequencing, the viral sequences of the three representative R. solani strains (Ilo-Rs-6, Tar-Rs-3, and Tar-Rs-5) from different rice-growing areas revealed the presence of at least 36 viruses or virus-like agents, with the Tar-Rs-3 strain harboring the largest number of viruses (at least 20 in total). These mycoviruses or their candidates are believed to have single-stranded RNA or dsRNA genomes and they belong to or are associated with the orders Martellivirales, Hepelivirales, Durnavirales, Cryppavirales, Ourlivirales, and Ghabrivirales based on their coding-complete RNA-dependent RNA polymerase sequences. The complete genome sequences of two novel RNA viruses belonging to the proposed family Phlegiviridae and family Mitoviridae were determined. en-copyright= kn-copyright= en-aut-name=UrzoMichael Louie R. en-aut-sei=Urzo en-aut-mei=Michael Louie R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GuintoTimothy D. en-aut-sei=Guinto en-aut-mei=Timothy D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Eusebio-CopeAna en-aut-sei=Eusebio-Cope en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BudotBernard O. en-aut-sei=Budot en-aut-mei=Bernard O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanoriaMary Jeanie T. en-aut-sei=Yanoria en-aut-mei=Mary Jeanie T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=JonsonGilda B. en-aut-sei=Jonson en-aut-mei=Gilda B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ArakawaMasao en-aut-sei=Arakawa en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Microbiology Division, Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Ba?os kn-affil= affil-num=2 en-affil=Microbiology Division, Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Ba?os kn-affil= affil-num=3 en-affil=Fit-for-Future Genetic Resources Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Ba?os kn-affil= affil-num=4 en-affil=Institute of Weed Science, Entomology, and Plant Pathology, College of Agriculture and Food Science, University of the Philippines Los Ba?os kn-affil= affil-num=5 en-affil=Traits for Challenged Environments Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Ba?os kn-affil= affil-num=6 en-affil=Traits for Challenged Environments Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Ba?os kn-affil= affil-num=7 en-affil=Faculty of Agriculture, Meijo University kn-affil= affil-num=8 en-affil=Plant-Microbe Interactions Group, Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= affil-num=9 en-affil=Plant-Microbe Interactions Group, Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=Rhizoctonia solani kn-keyword=Rhizoctonia solani en-keyword=dsRNA kn-keyword=dsRNA en-keyword=mycovirus kn-keyword=mycovirus en-keyword=RNA virus kn-keyword=RNA virus en-keyword=metatranscriptome kn-keyword=metatranscriptome END start-ver=1.4 cd-journal=joma no-vol=166 cd-vols= no-issue=8 article-no= start-page=bqaf102 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuromedin U Deficiency Disrupts Daily Testosterone Fluctuation and Reduces Wheel-running Activity in Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=The objective of this study was to elucidate the role of endogenous Neuromedin U (NMU) in rats by performing NMU knockout (KO). Male, but not female NMU KO rats exhibited decreased wheel-running activity vs wildtype (WT), although overall home cage activity was not affected. Plasma testosterone in WT rats varied significantly over the course of a day, with a peak at ZT1 and a nadir at ZT18, whereas in NMU KO rats testosterone remained stable throughout the day. Chronic administration of testosterone restored wheel-running activity in NMU KO rats to the same level as in WT rats, suggesting that the decrease in wheel-running activity in NMU KO rats is due to the disruption of the diurnal change of testosterone. Accordingly, expression of the luteinizing hormone beta subunit (Lhb) mRNA in the pars distalis of anterior pituitary was significantly lower in NMU KO rats; immunostaining revealed that the size of luteinizing hormone (LH)?expressing cells was also relatively small in those animals. In the brain of male WT rats, Nmu was highly expressed in the pars tuberalis, and the NMU receptor Nmur2 was highly expressed in the ependymal cell layer of the third ventricle. This study reveals a novel function of NMU and indicates that endogenous NMU in rats plays a role in the regulation of motivated activity via regulation of testosterone. en-copyright= kn-copyright= en-aut-name=OtsukaMai en-aut-sei=Otsuka en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeuchiYu en-aut-sei=Takeuchi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriyamaMaho en-aut-sei=Moriyama en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EgoshiSakura en-aut-sei=Egoshi en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotoYuki en-aut-sei=Goto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GuTingting en-aut-sei=Gu en-aut-mei=Tingting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimuraAtsushi P en-aut-sei=Kimura en-aut-mei=Atsushi P kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaraguchiShogo en-aut-sei=Haraguchi en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakeuchiSakae en-aut-sei=Takeuchi en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsuyamaMakoto en-aut-sei=Matsuyama en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=BentleyGeorge E en-aut-sei=Bentley en-aut-mei=George E kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AizawaSayaka en-aut-sei=Aizawa en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=Department of Biology, Faculty of Science, 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=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Department of Biological Sciences, Faculty of Science, Hokkaido University kn-affil= affil-num=8 en-affil=Department of Biochemistry, Showa University School of Medicine kn-affil= affil-num=9 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Division of Molecular Genetics, Shigei Medical Research Institute kn-affil= affil-num=12 en-affil=Department of Integrative Biology and Helen Wills Neuroscience Institute, University of California at Berkeley kn-affil= affil-num=13 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Neuromedin U kn-keyword=Neuromedin U en-keyword=rat kn-keyword=rat en-keyword=motivation kn-keyword=motivation en-keyword=activity kn-keyword=activity en-keyword=testosterone kn-keyword=testosterone en-keyword=wheel-running kn-keyword=wheel-running END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=生物学的製剤の使用は、関節リウマチに対する整形外科手術後の手術部位感染や創傷治癒遅延を増加させない kn-title=The use of biologic disease-modifying antirheumatic drugs does not increase surgical site infection or delayed wound healing after orthopaedic surgeries for rheumatoid arthritis en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KISOYohei en-aut-sei=KISO en-aut-mei=Yohei kn-aut-name=木曽洋平 kn-aut-sei=木曽 kn-aut-mei=洋平 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=214 cd-vols= no-issue= article-no= start-page=32 end-page=41 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Medaka approach to evolutionary social neuroscience en-subtitle= kn-subtitle= en-abstract= kn-abstract=Previously, the integration of comparative biological and neuroscientific approaches has led to significant advancements in social neuroscience. This review highlights the potential and future directions of evolutionary social neuroscience research utilizing medaka fishes (the family Adrianichthyidae) including Japanese medaka (Oryzias latipes). We focus on medaka social cognitive capabilities and mate choice behavior, particularly emphasizing mate preference using visual cues. Medaka fishes are also advantageous due to their abundant genetic resources, extensive genomic information, and the relative ease of laboratory breeding and genetic manipulation. Here we present some research examples of both the conventional neuroscience approach and evolutionary approach involving medaka fishes and other species. We also discuss the prospects of uncovering the molecular and cellular mechanisms underlying the diversity of visual mate preference among species. Especially, we introduce that the single-cell transcriptome technology, particularly in conjunction with 'Adaptive Circuitry Census', is an innovative tool that bridges comparative biological methods and neuroscientific approaches. Evolutionary social neuroscience research using medaka has the potential to unveil fundamental principles in neuroscience and elucidate the mechanisms responsible for generating diversity in mating strategies. en-copyright= kn-copyright= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Hiraki-KajiyamaTowako en-aut-sei=Hiraki-Kajiyama en-aut-mei=Towako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UedaRyutaro en-aut-sei=Ueda en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekiTakahide en-aut-sei=Seki en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YokoiSaori en-aut-sei=Yokoi en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatsumuraTakafumi en-aut-sei=Katsumura en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeuchiHideaki en-aut-sei=Takeuchi en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=3 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=4 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=5 en-affil=School of Pharmaceutical Sciences, Hokkaido University kn-affil= affil-num=6 en-affil=School of Medicine, Kitasato University kn-affil= affil-num=7 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= en-keyword=Evolutionary neuroscience kn-keyword=Evolutionary neuroscience en-keyword=Comparative neuroscience kn-keyword=Comparative neuroscience en-keyword=Medaka bioresource kn-keyword=Medaka bioresource en-keyword=Visual mate preference kn-keyword=Visual mate preference en-keyword=Sexual selection kn-keyword=Sexual selection en-keyword=Genetic manipulation kn-keyword=Genetic manipulation END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=2323 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A mini-hairpin shaped nascent peptide blocks translation termination by a distinct mechanism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Protein synthesis by ribosomes produces functional proteins but also serves diverse regulatory functions, which depend on the coding amino acid sequences. Certain nascent peptides interact with the ribosome exit tunnel to arrest translation and modulate themselves or the expression of downstream genes. However, a comprehensive understanding of the mechanisms of such ribosome stalling and its regulation remains elusive. In this study, we systematically screen for unidentified ribosome arrest peptides through phenotypic evaluation, proteomics, and mass spectrometry analyses, leading to the discovery of the arrest peptides PepNL and NanCL in E. coli. Our cryo-EM study on PepNL reveals a distinct arrest mechanism, in which the N-terminus of PepNL folds back towards the tunnel entrance to prevent the catalytic GGQ motif of the release factor from accessing the peptidyl transferase center, causing translation arrest at the UGA stop codon. Furthermore, unlike sensory arrest peptides that require an arrest inducer, PepNL uses tryptophan as an arrest inhibitor, where Trp-tRNATrp reads through the stop codon. Our findings illuminate the mechanism and regulatory framework of nascent peptide-induced translation arrest, paving the way for exploring regulatory nascent peptides. en-copyright= kn-copyright= en-aut-name=AndoYushin en-aut-sei=Ando en-aut-mei=Yushin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KoboAkinao en-aut-sei=Kobo en-aut-mei=Akinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NiwaTatsuya en-aut-sei=Niwa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamakawaAyako en-aut-sei=Yamakawa en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KonomaSuzuna en-aut-sei=Konoma en-aut-mei=Suzuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiYuki en-aut-sei=Kobayashi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NurekiOsamu en-aut-sei=Nureki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TaguchiHideki en-aut-sei=Taguchi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ItohYuzuru en-aut-sei=Itoh en-aut-mei=Yuzuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ChadaniYuhei en-aut-sei=Chadani en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=2 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=3 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=4 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=5 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=6 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=7 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=8 en-affil=School of Life Science and Technology, Institute of Science Tokyo kn-affil= affil-num=9 en-affil=Department of Biological Sciences, Graduate School of Science, The University of Tokyo kn-affil= affil-num=10 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=2 article-no= start-page=43 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250317 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Molecular Iodine-Catalyzed Synthesis of 3,3-Disubstituted Isatins: Total Synthesis of Indole Alkaloid, 3,3-Dimethoxy-2-oxindole en-subtitle= kn-subtitle= en-abstract= kn-abstract=3,3-Dialkoxy-2-oxindoles are prevalent in natural products and exhibit unique biological activities. Among them, acyclic alkoxy analogues show instability in acidic conditions, making access to acyclic isatin ketals highly challenging. Conventional methods for the synthesis of 3,3-dialkoxy-2-oxindoles usually require strongly acidic and harsh reaction conditions, resulting in a low overall efficiency. Herein, we report on an acid- and metal-free protocol for the synthesis of 3,3-dialkoxy-2-oxindoles from isatins through an iodine-catalyzed ketalization. This photochemical protocol does not require the use of any specific reagents such as metal catalysts. Furthermore, the total synthesis of an unprecedented 2-oxindole alkaloid bearing 3,3-dimethoxy moiety is achieved. en-copyright= kn-copyright= en-aut-name=TokushigeKeisuke en-aut-sei=Tokushige en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsaiShota en-aut-sei=Asai en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AbeTakumi en-aut-sei=Abe en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=School of Pharmacy, Shujitsu University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=3,3-dialkoxyisatins kn-keyword=3,3-dialkoxyisatins en-keyword=isatins kn-keyword=isatins en-keyword=ketalization kn-keyword=ketalization en-keyword=iodine kn-keyword=iodine en-keyword=indole alkaloid kn-keyword=indole alkaloid END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=4 article-no= start-page=e70139 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induction Therapy With Oral Tacrolimus Provides Long-Term Benefit in Thiopurine-Na?ve Refractory Ulcerative Colitis Patients Despite Low Serum Albumin Levels en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: Oral tacrolimus is an effective treatment for refractory ulcerative colitis (UC). However, tacrolimus is underutilized because of the difficulties in transitioning to subsequent maintenance therapy and concerns about adverse events.
Methods: We evaluated the clinical outcomes, adverse events, and accumulated medication costs in consecutive 72 UC patients treated with tacrolimus.
Results: Fifty-five (76%) patients with pancolitis and 43 (60%) patients with acute severe disease were entered. Fifty-four (75%) achieved clinical remission 8 weeks after starting tacrolimus. At the last visit, 62 (86%) patients had colectomy-free remission, and 55 (76%) patients had corticosteroid-free remission. Eighteen (25%) patients maintained remission without additional treatment after tacrolimus discontinuation. Patients with continuous remission had a significantly lower history of thiopurine use and lower serum albumin levels at the induction of tacrolimus than patients with failure to induce or maintain remission. No severe adverse events due to tacrolimus treatment were observed. The accumulated medication costs over 3 years in patients with continuous remission after the start of tacrolimus were lower than those in patients with induction and maintenance of infliximab (p < 0.001).
Conclusions: Tacrolimus could have an irreplaceable role in the era of biologic therapies, especially for refractory UC patients with thiopurine-na & iuml;ve and low serum albumin levels. en-copyright= kn-copyright= en-aut-name=IgawaShoko en-aut-sei=Igawa en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InokuchiToshihiro en-aut-sei=Inokuchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ToyosawaJunki en-aut-sei=Toyosawa en-aut-mei=Junki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AoyamaYuki en-aut-sei=Aoyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KinugasaHideaki en-aut-sei=Kinugasa en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=biologics therapy kn-keyword=biologics therapy en-keyword=tacrolimus kn-keyword=tacrolimus en-keyword=thiopurine kn-keyword=thiopurine en-keyword=ulcerative colitis kn-keyword=ulcerative colitis END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=10462 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250326 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontal pathogen Porphyromonas gingivalis (P. gingivalis) is believed to possess immune evasion capabilities, but it remains unclear whether this immune evasion is related to host gene alternative splicing (AS). In this study, RNA-sequencing revealed significant changes in both AS landscape and transcriptomic profile of macrophages following P. gingivalis infection with/without knockout of gingipain (a unique toxic protease of P. gingivalis). P. gingivalis infection increased the PD-L1 transcripts expression and selectively upregulated a specific coding isoform that more effectively binds to PD-1 on T cells, thereby inhibiting immune function. Biological experiments also detected AS switch of PD-L1 in P. gingivalis-infected or gingipain-treated macrophages. AlphaFold 3 predictions indicated that the protein docking compatibility between PD-1 and P. gingivalis-upregulated PD-L1 isoform was over 80% higher than another coding isoform. These findings suggest that P. gingivalis employs gingipain to modulate the AS of PD-L1, facilitating immune evasion. en-copyright= kn-copyright= en-aut-name=ZhengYilin en-aut-sei=Zheng en-aut-mei=Yilin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WengYao en-aut-sei=Weng en-aut-mei=Yao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SitosariHeriati en-aut-sei=Sitosari en-aut-mei=Heriati kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HeYuhan en-aut-sei=He en-aut-mei=Yuhan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhangXiu en-aut-sei=Zhang en-aut-mei=Xiu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShiotsuNoriko en-aut-sei=Shiotsu en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FukuharaYoko en-aut-sei=Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkegameMika en-aut-sei=Ikegame en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkamuraHirohiko en-aut-sei=Okamura en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=7 en-affil=Comprehensive Dental Clinic, Okayama University Hospital, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=Gingipain kn-keyword=Gingipain en-keyword=Macrophage kn-keyword=Macrophage en-keyword=Alternative splicing kn-keyword=Alternative splicing en-keyword=PD-L1 kn-keyword=PD-L1 en-keyword=Immune evasion kn-keyword=Immune evasion END start-ver=1.4 cd-journal=joma no-vol=301 cd-vols= no-issue=4 article-no= start-page=108334 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of basic amino acid residues in substrate binding and transport of the light-driven anion pump Synechocystis halorhodopsin (SyHR) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Microbial rhodopsins are photoreceptive seventransmembrane a-helical proteins, many of which function as ion transporters, primarily for small monovalent ions such as Na+, K+, Cl-, Br-, and I-. Synechocystis halorhodopsin (SyHR), identified from the cyanobacterium Synechocystis sp. PCC 7509, uniquely transports the polyatomic divalent SO42- inward, in addition to monovalent anions (Cl- and Br-). In this study, we conducted alanine-scanning mutagenesis on twelve basic amino acid residues to investigate the anion transport mechanism of SyHR. We quantitatively evaluated the Cl-and SO42- transport activities of the WT SyHR and its mutants. The results showed a strong correlation between the Cl-and SO42- transport activities among them (R = 0.94), suggesting a shared pathway for both anions. Notably, the R71A mutation selectively abolished SO42- transport activity while maintaining Cl- transport, whereas the H167A mutation significantly impaired both Cl-and SO42- transport. Furthermore, spectroscopic analysis revealed that the R71A mutant lost its ability to bind SO42- due to the absence of a positive charge, while the H167A mutant failed to accumulate the O intermediate during the photoreaction cycle (photocycle) due to reduced hydrophilicity. Additionally, computational analysis revealed the SO42- binding modes and clarified the roles of residues involved in its binding around the retinal chromophore. Based on these findings and previous structural information, we propose that the positive charge and hydrophilicity of Arg71 and His167 are crucial for the formation of the characteristic initial and transient anion-binding site of SyHR, enabling its unique ability to bind and transport both Cl-and SO42-. en-copyright= kn-copyright= en-aut-name=NakamaMasaki en-aut-sei=Nakama en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 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=6 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, The University of Tokyo kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Applied Chemistry, The University of Tokyo kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=microbial rhodopsin kn-keyword=microbial rhodopsin en-keyword=anion transport kn-keyword=anion transport en-keyword=retinal kn-keyword=retinal en-keyword=membrane protein kn-keyword=membrane protein en-keyword=photobiology kn-keyword=photobiology END start-ver=1.4 cd-journal=joma no-vol=125 cd-vols= no-issue= article-no= start-page=106672 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways en-subtitle= kn-subtitle= en-abstract= kn-abstract=Resveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At concentrations of 25-50 mu M, resveratrol increased autophagy as measured by microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I ratio and enhanced lysosomal activity as assessed by a lysosomal activity reporter system. RNA sequencing revealed upregulation of lysosomal and autophagy-related genes, including cathepsins. Furthermore, reporter assays showed resveratrol's activation of antioxidant response via nuclear factor erythroid 2-related factor 2 (NRF2)mediated, leading to upregulation of transcription factor EB/transcription factor E3 (TFEB/TFE3), master regulators of lysosomal function. In fibroblasts pre-loaded with melanosomes, resveratrol reduced melanosome content compared to control by day 3. The findings reveal the activation of interconnected autophagy, lysosomal, and antioxidant pathways by resveratrol, suggesting potential applications in functional foods targeting dermal hyperpigmentation. en-copyright= kn-copyright= en-aut-name=OkamotoSaki en-aut-sei=Okamoto en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KakimaruSaya en-aut-sei=Kakimaru en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoreishiMayuko en-aut-sei=Koreishi en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakamotoMika en-aut-sei=Sakamoto en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoHideya en-aut-sei=Ando en-aut-mei=Hideya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujinoYoshio en-aut-sei=Tsujino en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University 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=National Institute of Genetics, ROIS kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Applied Chemistry and Biotechnology, Okayama University of Science kn-affil= affil-num=7 en-affil=Graduate School of Science, Technology, and Innovation, Kobe University kn-affil= affil-num=8 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Antioxidant kn-keyword=Antioxidant en-keyword=Lysosomes kn-keyword=Lysosomes en-keyword=Autophagy kn-keyword=Autophagy en-keyword=Resveratrol kn-keyword=Resveratrol en-keyword=Skin fibroblasts kn-keyword=Skin fibroblasts en-keyword=Bioactive compounds kn-keyword=Bioactive compounds END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=52 article-no= start-page=35202 end-page=35213 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bright Quantum-Grade Fluorescent Nanodiamonds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Optically accessible spin-active nanomaterials are promising as quantum nanosensors for probing biological samples. However, achieving bioimaging-level brightness and high-quality spin properties for these materials is challenging and hinders their application in quantum biosensing. Here, we demonstrate bright fluorescent nanodiamonds (NDs) containing 0.6?1.3-ppm negatively charged nitrogen-vacancy (NV) centers by spin-environment engineering via enriching spin-less 12C-carbon isotopes and reducing substitutional nitrogen spin impurities. The NDs, readily introduced into cultured cells, exhibited improved optically detected magnetic resonance (ODMR) spectra; peak splitting (E) was reduced by 2?3 MHz, and microwave excitation power required was 20 times lower to achieve a 3% ODMR contrast, comparable to that of conventional type-Ib NDs. They show average spin-relaxation times of T1 = 0.68 ms and T2 = 3.2 μs (1.6 ms and 5.4 μs maximum) that were 5- and 11-fold longer than those of type-Ib, respectively. Additionally, the extended T2 relaxation times of these NDs enable shot-noise-limited temperature measurements with a sensitivity of approximately 0.28K/√Hz. The combination of bulk-like NV spin properties and enhanced fluorescence significantly improves the sensitivity of ND-based quantum sensors for biological applications. en-copyright= kn-copyright= en-aut-name=OshimiKeisuke en-aut-sei=Oshimi en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiwataHitoshi en-aut-sei=Ishiwata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakashimaHiromu en-aut-sei=Nakashima en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Mandi?Sara en-aut-sei=Mandi? en-aut-mei=Sara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHina en-aut-sei=Kobayashi en-aut-mei=Hina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TeramotoMinori en-aut-sei=Teramoto en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujiHirokazu en-aut-sei=Tsuji en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishibayashiYoshiki en-aut-sei=Nishibayashi en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShikanoYutaka en-aut-sei=Shikano en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AnToshu en-aut-sei=An en-aut-mei=Toshu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraMasazumi en-aut-sei=Fujiwara en-aut-mei=Masazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=The National Institutes for Quantum Science and Technology (QST), Institute for Quantum Life Science (iQLS) kn-affil= affil-num=3 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. kn-affil= affil-num=7 en-affil=Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. kn-affil= affil-num=8 en-affil=Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. kn-affil= affil-num=9 en-affil=Institute of Systems and Information Engineering, University of Tsukuba kn-affil= affil-num=10 en-affil=School of Materials Science, Japan Advanced Institute of Science and Technology kn-affil= affil-num=11 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= en-keyword=nanodiamonds kn-keyword=nanodiamonds en-keyword=nitrogen-vacancy centers kn-keyword=nitrogen-vacancy centers en-keyword=spins kn-keyword=spins en-keyword=spin-relaxation times kn-keyword=spin-relaxation times en-keyword=quantum biosensor kn-keyword=quantum biosensor en-keyword=cellular probes kn-keyword=cellular probes END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=24 article-no= start-page=2045 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=iPSC-Derived Biological Pacemaker-From Bench to Bedside en-subtitle= kn-subtitle= en-abstract= kn-abstract=Induced pluripotent stem cell (iPSC)-derived biological pacemakers have emerged as an alternative to traditional electronic pacemakers for managing cardiac arrhythmias. While effective, electronic pacemakers face challenges such as device failure, lead complications, and surgical risks, particularly in children. iPSC-derived pacemakers offer a promising solution by mimicking the sinoatrial node's natural pacemaking function, providing a more physiological approach to rhythm control. These cells can differentiate into cardiomyocytes capable of autonomous electrical activity, integrating into heart tissue. However, challenges such as achieving cellular maturity, long-term functionality, and immune response remain significant barriers to clinical translation. Future research should focus on refining gene-editing techniques, optimizing differentiation, and developing scalable production processes to enhance the safety and effectiveness of these biological pacemakers. With further advancements, iPSC-derived pacemakers could offer a patient-specific, durable alternative for cardiac rhythm management. This review discusses key advancements in differentiation protocols and preclinical studies, demonstrating their potential in treating dysrhythmias. en-copyright= kn-copyright= en-aut-name=VoQuan Duy en-aut-sei=Vo en-aut-mei=Quan Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IidaToshihiro en-aut-sei=Iida en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=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=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=sinoatrial node kn-keyword=sinoatrial node en-keyword=HCN channels kn-keyword=HCN channels en-keyword=induced pluripotent stem cell kn-keyword=induced pluripotent stem cell END start-ver=1.4 cd-journal=joma no-vol=169 cd-vols= no-issue=1 article-no= start-page=e16291 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241222 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exploring the Role of Ccn3 in Type III Cell of Mice Taste Buds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Different taste cells express unique cell-type markers, enabling researchers to distinguish them and study their functional differentiation. Using single-cell RNA-Seq of taste cells in mouse fungiform papillae, we found that Cellular Communication Network Factor 3 (Ccn3) was highly expressed in Type III taste cells but not in Type II taste cells. Ccn3 is a protein-coding gene involved in various biological processes, such as cell proliferation, angiogenesis, tumorigenesis, and wound healing. Therefore, in this study, we aimed to explore the expression and function of Ccn3 in mouse taste bud cells. Using reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry (IHC), we confirmed that Ccn3 was predominantly expressed in Type III taste cells. Through IHC, quantitative real-time RT-PCR, gustatory nerve recordings, and short-term lick tests, we observed that Ccn3 knockout (Ccn3-KO) mice did not exhibit any significant differences in the expression of taste cell markers and taste responses compared to wild-type controls. To explore the function of Ccn3 in taste cells, bioinformatics analyses were conducted and predicted possible roles of Ccn3 in tissue regeneration, perception of pain, protein secretion, and immune response. Among them, an immune function is the most plausible based on our experimental results. In summary, our study indicates that although Ccn3 is strongly expressed in Type III taste cells, its knockout did not influence the basic taste response, but bioinformatics provided valuable insights into the possible role of Ccn3 in taste buds and shed light on future research directions. en-copyright= kn-copyright= en-aut-name=WangKuanyu en-aut-sei=Wang en-aut-mei=Kuanyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HorieKengo en-aut-sei=Horie en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=bioinformatics kn-keyword=bioinformatics en-keyword=Ccn3 kn-keyword=Ccn3 en-keyword=Type III taste cell kn-keyword=Type III taste cell END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=3 article-no= start-page=769 end-page=774 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Review: Nicotinic acetylcholine receptors to regulate important brain activity?what occurs at the molecular level? en-subtitle= kn-subtitle= en-abstract= kn-abstract=Herein, we briefly review the role of nicotinic acetylcholine receptors in regulating important brain activity by controlled release of acetylcholine from subcortical neuron groups, focusing on a microscopic viewpoint and considering the nonlinear dynamics of biological macromolecules associated with neuron activity and how they give rise to advanced brain functions of brain. en-copyright= kn-copyright= en-aut-name=NaraShigetoshi en-aut-sei=Nara en-aut-mei=Shigetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamagutiYutaka en-aut-sei=Yamaguti en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsudaIchiro en-aut-sei=Tsuda en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Information Engineering, Fukuoka Institute of Technology kn-affil= affil-num=3 en-affil=Chubu University Academy of Emerging Sciences/Center for Mathematical Science and Artificial Intelligence, Chubu University kn-affil= en-keyword=Neuromodulator kn-keyword=Neuromodulator en-keyword=Nichotinic kn-keyword=Nichotinic en-keyword=Acetylcholine kn-keyword=Acetylcholine en-keyword=Receptors kn-keyword=Receptors en-keyword=Brain activity kn-keyword=Brain activity END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page=1 end-page=8 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=2023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transepidermal Water Loss Estimation Model for Evaluating Skin Barrier Function en-subtitle= kn-subtitle= en-abstract= kn-abstract=Deterioration of skin barrier function causes symptoms such as allergies because it allows various chemical substances to enter the human body. Quantitative evaluation of the thickness and water content of the stratum corneum is useful as a measure of skin barrier function in fields such as dermatology, nursing science, and cosmetics development. The stratum corneum is responsible for most of the skin barrier function, and this function has conventionally been evaluated using transepidermal water loss (TEWL). In this paper, we propose a new model for estimation of TEWL from measurements of the thickness of the stratum corneum and water content of the surface of the stratum corneum, and discuss the results of the measurements. By measuring the thickness and water content of the stratum corneum using confocal laser microscopy and confocal Raman spectroscopy, respectively, and examining the relationship of these variables with TEWL, we established a new potential model for estimating TEWL from these two variables. The correlation coefficient of the validation data was 0.886 and the root mean squared error was 8.18 points. These findings indicate the feasibility of qualitative evaluation of TEWL by measuring the thickness and water content of the stratum corneum. en-copyright= kn-copyright= en-aut-name=UeharaOsamu en-aut-sei=Uehara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KusuharaToshimasa en-aut-sei=Kusuhara en-aut-mei=Toshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraTakao en-aut-sei=Nakamura en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Medical Engineering Laboratory, ALCARE Co., Ltd. kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=TEWL kn-keyword=TEWL en-keyword=stratum corneum thickness kn-keyword=stratum corneum thickness en-keyword=water content of stratum corneum kn-keyword=water content of stratum corneum END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=4 article-no= start-page=213 end-page=218 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=β-catenin Binds to Gsk-3β in Liquid-Liquid Phase Separation Compartment in HEK293 Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Liquid-liquid phase separation (LLPS) has emerged as a significant mechanism for cellular organization, impacting various biological processes, including Wnt/β-catenin signaling. This study investigates the role of LLPS in the regulation of β-catenin in HEK293 cells, particularly in response to Wnt3a signaling. Our findings demonstrate that β-catenin is regulated by LLPS, forming spherical droplets indicative of this phenomenon. Fluorescence recovery after photobleaching (FRAP) assays revealed that these droplets exhibit reversible dynamics, further confirming their phase-separated nature. Importantly, treatment with Wnt3a led to an increase in β-catenin levels, while simultaneously reducing the recovery of fluorescence intensity in FRAP experiments, suggesting that enhanced Wnt signaling may stimulate the release of β-catenin from LLPS. Immunoprecipitation studies indicated that β-catenin binds to glycogen synthase kinase 3β (Gsk-3β) within the LLPS state, highlighting a potential regulatory mechanism whereby LLPS facilitates the phosphorylation and subsequent degradation of β-catenin. The addition of 1,6-hexanediol disrupted the β-catenin/Gsk-3β interaction, reinforcing the idea that LLPS plays a critical role in modulating these biochemical interactions. The findings presented in this study suggest that LLPS is not only crucial for the spatial organization of β-catenin but also serves as a regulatory mechanism for its signaling functions in the Wnt pathway. Given the association of aberrant Wnt signaling with various diseases, including cancer and neurodegenerative disorders, understanding the role of LLPS in this context may provide new insights into therapeutic strategies targeting these pathological conditions. en-copyright= kn-copyright= en-aut-name=KatoMari en-aut-sei=Kato en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanaiAiri en-aut-sei=Tanai en-aut-mei=Airi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuharaYoko en-aut-sei=Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhengXinyu en-aut-sei=Zheng en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SitosariHeriati en-aut-sei=Sitosari en-aut-mei=Heriati kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkegameMika en-aut-sei=Ikegame en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamuraHirohiko en-aut-sei=Okamura en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=β-catenin kn-keyword=β-catenin en-keyword=Gsk-3β kn-keyword=Gsk-3β en-keyword=LLPS kn-keyword=LLPS en-keyword=Wnt kn-keyword=Wnt END start-ver=1.4 cd-journal=joma no-vol=161 cd-vols= no-issue=21 article-no= start-page=214501 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The nature of the hydrophobic interaction varies as the solute size increases from methane’s to C60’s en-subtitle= kn-subtitle= en-abstract= kn-abstract=The hydrophobic interaction, often combined with the hydrophilic or ionic interactions, makes the behavior of aqueous solutions very rich and plays an important role in biological systems. Theoretical and computer simulation studies have shown that the water-mediated force depends strongly on the size and other chemical properties of the solute, but how it changes with these factors remains unclear. We report here a computer simulation study that illustrates how the hydrophobic pair interaction and the entropic and enthalpic terms change with the solute size when the solute?solvent weak attractive interaction is unchanged with the solute size. The nature of the hydrophobic interaction changes qualitatively as the solute size increases from that of methane to that of fullerene. The potential of mean force between small solutes has several well-defined extrema, including the third minimum, whereas the potential of mean force between large solutes has the deep contact minimum and the large free-energy barrier between the contact and the water-bilayer separated configurations. The difference in the potential of mean force is related to the differences in the water density, energy, and hydrogen bond number distributions in the vicinity of the pairs of hydrophobic solutes. en-copyright= kn-copyright= en-aut-name=NaitoHidefumi en-aut-sei=Naito en-aut-mei=Hidefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SumiTomonari en-aut-sei=Sumi en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KogaKenichiro en-aut-sei=Koga en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Faculty of Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=6 article-no= start-page=469 end-page=474 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Treatment of Tenosynovial Giant Cell Tumor of the Cervical Spine with Postoperative Anti-RANKL Antibody (Denosumab) Administration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tenosynovial giant cell tumor (TGCT) is a fibrous histiocytic tumor originating in the synovial membrane. While cervical TGCT may not be considered a common diagnosis preoperatively because it is relatively rare, it has a high recurrence rate and should be considered. Total resection is preferable, but it can be challenging due to the risk of damaging the vertebral artery. Denosumab has shown effectiveness as a postoperative treatment for osteolytic bone lesion. Denosumab administration coupled with close follow-up might offer an effective postoperative treatment option for unresectable TGCT with bone invasion. en-copyright= kn-copyright= en-aut-name=HirataYuichi en-aut-sei=Hirata en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaseTakayuki en-aut-sei=Nagase en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasadaSusumu en-aut-sei=Sasada en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AyadaYoshiyuki en-aut-sei=Ayada en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyakeHayato en-aut-sei=Miyake en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugaharaChiaki en-aut-sei=Sugahara en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OdaYoshinao en-aut-sei=Oda en-aut-mei=Yoshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= 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 Pathology and Oncology, 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= affil-num=7 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=tenosynovial giant cell tumor kn-keyword=tenosynovial giant cell tumor en-keyword=bone tumor kn-keyword=bone tumor en-keyword=spine kn-keyword=spine END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=11 article-no= start-page=e70476 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic Introgression in the Hybrid zones at the Margins of the Species' Range Between Ecologically Distinct Rubus Species en-subtitle= kn-subtitle= en-abstract= kn-abstract=Populations in extreme environments at the margins of a species' range are often the most vulnerable to climate change, but they may also experience novel evolutionary processes, such as secondary contact and hybridization with their relatives. The range overlap resulting from secondary contact with related species that have adapted to different climatic zones may act as corridors for adaptive introgression. To test this hypothesis, we examined the hybrid zones along the altitude of two closely related Rubus species, one temperate and the other subtropical species, at their southern and northern limits on Yakushima Island, Japan. Genomic cline analysis revealed non-neutral introgression throughout the genome in both directions in the two species. Some of these genomic regions involve gene ontology terms related to the regulation of several biological processes. Our niche modeling suggests that, assuming niche conservatism, the temperate species are likely to lose their suitable habitat, and the backcrossed hybrids with the subtropical species are already expanding upslope on the island. Adaptive introgression through the hybrid zone may contribute to the persistence and expansion of the species in the southernmost and northernmost populations. en-copyright= kn-copyright= en-aut-name=MimuraMakiko en-aut-sei=Mimura en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TangZhenxing en-aut-sei=Tang en-aut-mei=Zhenxing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShigenobuShuji en-aut-sei=Shigenobu en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamaguchiKatsushi en-aut-sei=Yamaguchi en-aut-mei=Katsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YaharaTetsukazu en-aut-sei=Yahara en-aut-mei=Tetsukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Biology, Okayama University kn-affil= affil-num=2 en-affil=Department of Biology, Okayama University kn-affil= affil-num=3 en-affil=Trans-Omics Facility, National Institute of Basic Biology kn-affil= affil-num=4 en-affil=Trans-Omics Facility, National Institute of Basic Biology kn-affil= affil-num=5 en-affil=Kyushu Open University kn-affil= en-keyword=adaptive introgression kn-keyword=adaptive introgression en-keyword=climate change kn-keyword=climate change en-keyword=hybrid zone kn-keyword=hybrid zone en-keyword=secondary contact kn-keyword=secondary contact END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=2 article-no= start-page=292 end-page=305 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The role of C1orf50 in breast cancer progression and prognosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although the prognosis of breast cancer has significantly improved compared to other types of cancer, there are still some patients who expire due to recurrence or metastasis. Therefore, it is necessary to develop a method to identify patients with poor prognosis at the early stages of cancer. In the process of discovering new prognostic markers from genes of unknown function, we found that the expression of C1orf50 determines the prognosis of breast cancer patients, especially for those with Luminal A breast cancer. This study aims to elucidate the molecular role of C1orf50 in breast cancer progression. Bioinformatic analyses of the breast cancer dataset of TCGA, and in vitro analyses, reveal the molecular pathways influenced by C1orf50 expression. C1orf50 knockdown suppressed the cell cycle of breast cancer cells and weakened their ability to maintain the undifferentiated state and self-renewal capacity. Interestingly, upregulation of C1orf50 increased sensitivity to CDK4/6 inhibition. In addition, C1orf50 was found to be more abundant in breast cancer cells than in normal breast epithelium, suggesting C1orf50’s involvement in breast cancer pathogenesis. Furthermore, the mRNA expression level of C1orf50 was positively correlated with the expression of PD-L1 and its related factors. These results suggest that C1orf50 promotes breast cancer progression through cell cycle upregulation, maintenance of cancer stemness, and immune evasion mechanisms. Our study uncovers the biological functions of C1orf50 in Luminal breast cancer progression, a finding not previously reported in any type of cancer. en-copyright= kn-copyright= en-aut-name=OtaniYusuke en-aut-sei=Otani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaAtsushi en-aut-sei=Tanaka en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaekawaMasaki en-aut-sei=Maekawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Pe?aTirso en-aut-sei=Pe?a en-aut-mei=Tirso kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RogachevskayaAnna en-aut-sei=Rogachevskaya en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoTeruhiko en-aut-sei=Ando en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatayamaHaruyoshi en-aut-sei=Katayama en-aut-mei=Haruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=RoehrlMichael H. en-aut-sei=Roehrl en-aut-mei=Michael H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=2 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=3 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=4 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=13 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=14 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=Luminal A breast cancer kn-keyword=Luminal A breast cancer en-keyword=Cell cycle kn-keyword=Cell cycle en-keyword=Immune evasion kn-keyword=Immune evasion en-keyword=YAP/TAZ kn-keyword=YAP/TAZ END start-ver=1.4 cd-journal=joma no-vol=300 cd-vols= no-issue=6 article-no= start-page=107360 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202406 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nonspecific N-terminal tetrapeptide insertions disrupt the translation arrest induced by ribosome-arresting peptide sequences en-subtitle= kn-subtitle= en-abstract= kn-abstract=The nascent polypeptide chains passing through the ribosome tunnel not only serve as an intermediate of protein synthesis but also, in some cases, act as dynamic genetic information, controlling translation through interaction with the ribosome. One notable example is Escherichia coli SecM, in which translation of the ribosome arresting peptide (RAP) sequence in SecM leads to robust elongation arrest. Translation regulations, including the SecM-induced translation arrest, play regulatory roles such as gene expression control. Recent investigations have indicated that the insertion of a peptide sequence, SKIK (or MSKIK), into the adjacent N-terminus of the RAP sequence of SecM behaves as an "arrest canceler". As the study did not provide a direct assessment of the strength of translation arrest, we conducted detailed biochemical analyses. The results revealed that the effect of SKIK insertion on weakening SecM-induced translation arrest was not specific to the SKIK sequence, that is, other tetrapeptide sequences inserted just before the RAP sequence also attenuated the arrest. Our data suggest that SKIK or other tetrapeptide insertions disrupt the context of the RAP sequence rather than canceling or preventing the translation arrest. en-copyright= kn-copyright= en-aut-name=KoboAkinao en-aut-sei=Kobo en-aut-mei=Akinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaguchiHideki en-aut-sei=Taguchi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChadaniYuhei en-aut-sei=Chadani en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=2 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=318 end-page=326 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Region-Specific Material Properties of Patellar Tendon on the Magnitude and Distribution of Local Stress and Strain en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effects of the region-specific material properties of the patellar tendon (PT) on the magnitude and distribution of local stress and strain are poorly understood. Hence, this study investigated this issue using finite element analysis. A three-dimensional PT model was developed based on parameters obtained from previous studies, and was bisected in the frontal plane. Two models were created: one that considered region-specific material properties (two-material model) and one that did not (one-material model). An 8% strain was applied to the proximal surface, and the mean and peak first principal stress and strain were calculated. In the two-material model, the mean first principal stress observed in the anterior region was 28.5% higher than that in the posterior region. However, in the one-material model, the mean first principal stress in the anterior region was 19.5% lower than that in the posterior region. Focusing on the differences between the models, the mean and peak first principal stresses in the posterior region of the one-material model were 61.1% and 41.2% higher, respectively, compared with those in the two-material model. Furthermore, the mean and peak first principal stresses in the proximal and distal regions of the posterior region in the one-material model were 41.8-75.8% higher than those in the two-material model. These results suggest that the region-specific material properties of PT influence the stress distribution and underscore the importance of modeling that incorporates region-specific material properties in PT finite element models. en-copyright= kn-copyright= en-aut-name=EnomotoShota en-aut-sei=Enomoto en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OdaToshiaki en-aut-sei=Oda en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Institute for Promotion of Education and Campus Life, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Education, Hyogo University of Teacher Education kn-affil= en-keyword=computational model kn-keyword=computational model en-keyword=Mooney-Rivlin model kn-keyword=Mooney-Rivlin model en-keyword=soft tissue. kn-keyword=soft tissue. END start-ver=1.4 cd-journal=joma no-vol=300 cd-vols= no-issue=3 article-no= start-page=105679 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Methyl vinyl ketone and its analogs covalently modify PI3K and alter physiological functions by inhibiting PI3K signaling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reactive carbonyl species (RCS), which are abundant in the environment and are produced in vivo under stress, covalently bind to nucleophilic residues such as Cys in proteins. Disruption of protein function by RCS exposure is predicted to play a role in the development of various diseases such as cancer and metabolic disorders, but most studies on RCS have been limited to simple cytotoxicity validation, leaving their target proteins and resulting physiological changes unknown. In this study, we focused on methyl vinyl ketone (MVK), which is one of the main RCS found in cigarette smoke and exhaust gas. We found that MVK suppressed PI3K-Akt signaling, which regulates processes involved in cellular homeostasis, including cell proliferation, autophagy, and glucose metabolism. Interestingly, MVK inhibits the interaction between the epidermal growth factor receptor and PI3K. Cys656 in the SH2 domain of the PI3K p85 subunit, which is the covalently binding site of MVK, is important for this interaction. Suppression of PI3K- Akt signaling by MVK reversed epidermal growth factor- induced negative regulation of autophagy and attenuated glucose uptake. Furthermore, we analyzed the effects of the 23 RCS compounds with structures similar to MVK and showed that their analogs also suppressed PI3K-Akt signaling in a manner that correlated with their similarities to MVK. Our study demonstrates the mechanism of MVK and its analogs in suppressing PI3K-Akt signaling and modulating physiological functions, providing a model for future studies analyzing environmental reactive species. en-copyright= kn-copyright= en-aut-name=MorimotoAtsushi en-aut-sei=Morimoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PanYuexuan en-aut-sei=Pan en-aut-mei=Yuexuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaSho en-aut-sei=Kubota en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DohmaeNaoshi en-aut-sei=Dohmae en-aut-mei=Naoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AbikoYumi en-aut-sei=Abiko en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UchidaKoji en-aut-sei=Uchida en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KumagaiYoshito en-aut-sei=Kumagai en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=6 en-affil=Graduate School of Biomedical Science, Nagasaki University kn-affil= affil-num=7 en-affil=Laboratory of Food Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo kn-affil= affil-num=8 en-affil=Graduate School of Pharmaceutical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=phosphatidylinositol 3-kinase (PI 3-kinase) kn-keyword=phosphatidylinositol 3-kinase (PI 3-kinase) en-keyword=cell signaling kn-keyword=cell signaling en-keyword=chemical modification kn-keyword=chemical modification en-keyword=autophagy kn-keyword=autophagy en-keyword=glucose uptake kn-keyword=glucose uptake END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=24968 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Apolipoprotein-B mRNA-editing complex 3B could be a new potential therapeutic target in endometriosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the correlation of Apolipoprotein-B mRNA-editing complex 3B (APOBEC3B) expression with hypoxia inducible factor 1α (HIF-1α), Kirsten rat sarcoma virus (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in endometriosis patients, and the inhibitory effects of APOBEC3B knockdown in a human endometriotic cell line. Here, APOBEC3B, HIF-1α, KRAS, and PIK3CA were examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR). The apoptosis, cell proliferation, invasion, migration, and biological function of APOBEC3B knockdown were explored in 12Z immortalized human endometriotic cell line. We observed APOBEC3B, HIF-1α, KRAS and PIK3CA expressions were significantly higher in endometriosis patients (p? T:A transition is minor. On the other hand, the gamma-irradiated DNA shows mainly G:C <-> T:A transversion. These results suggest that carbon ion beams produce complex DNA damage, and gamma-rays are prone to single oxidative base damage, such as 8-oxoguanine. Carbon ion beams can also introduce oxidative base damage, and the damage species is 5-hydroxycytosine. This was consistent with our previous results of DNA damage caused by heavy ion beams. We confirmed the causal DNA damage by mass spectrometry for these mutations. en-copyright= kn-copyright= en-aut-name=TokuyamaYuka en-aut-sei=Tokuyama en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriKanae en-aut-sei=Mori en-aut-mei=Kanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IsobeMidori en-aut-sei=Isobe en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TeratoHiroaki en-aut-sei=Terato en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Analytical Research Center for Experimental Science, Saga University kn-affil= affil-num=2 en-affil=Analytical Research Center for Experimental Science, Saga University kn-affil= affil-num=3 en-affil=Advanced Science Research Center, Okayama University kn-affil= affil-num=4 en-affil=Advanced Science Research Center, Okayama University kn-affil= en-keyword=base damage kn-keyword=base damage en-keyword=mutation kn-keyword=mutation en-keyword=gamma-rays kn-keyword=gamma-rays en-keyword=heavy ion beam kn-keyword=heavy ion beam END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=4610 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An NLR paralog Pit2 generated from tandem duplication of Pit1 fine-tunes Pit1 localization and function en-subtitle= kn-subtitle= en-abstract= kn-abstract=NLR family proteins act as intracellular receptors. Gene duplication amplifies the number of NLR genes, and subsequent mutations occasionally provide modifications to the second gene that benefits immunity. However, evolutionary processes after gene duplication and functional relationships between duplicated NLRs remain largely unclear. Here, we report that the rice NLR protein Pit1 is associated with its paralogue Pit2. The two are required for the resistance to rice blast fungus but have different functions: Pit1 induces cell death, while Pit2 competitively suppresses Pit1-mediated cell death. During evolution, the suppression of Pit1 by Pit2 was probably generated through positive selection on two fate-determining residues in the NB-ARC domain of Pit2, which account for functional differences between Pit1 and Pit2. Consequently, Pit2 lost its plasma membrane localization but acquired a new function to interfere with Pit1 in the cytosol. These findings illuminate the evolutionary trajectory of tandemly duplicated NLR genes after gene duplication. en-copyright= kn-copyright= en-aut-name=LiYuying en-aut-sei=Li en-aut-mei=Yuying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangQiong en-aut-sei=Wang en-aut-mei=Qiong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JiaHuimin en-aut-sei=Jia en-aut-mei=Huimin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KosamiKen-Ichi en-aut-sei=Kosami en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UebaTakahiro en-aut-sei=Ueba en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujimotoAtsumi en-aut-sei=Tsujimoto en-aut-mei=Atsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamanakaMiki en-aut-sei=Yamanaka en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YabumotoYasuyuki en-aut-sei=Yabumoto en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MikiDaisuke en-aut-sei=Miki en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SasakiEriko en-aut-sei=Sasaki en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FukaoYoichiro en-aut-sei=Fukao en-aut-mei=Yoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraMasayuki en-aut-sei=Fujiwara en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Kaneko-KawanoTakako en-aut-sei=Kaneko-Kawano en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanLi en-aut-sei=Tan en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KojimaChojiro en-aut-sei=Kojima en-aut-mei=Chojiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WingRod A. en-aut-sei=Wing en-aut-mei=Rod A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SebastianAlfino en-aut-sei=Sebastian en-aut-mei=Alfino kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NishimuraHideki en-aut-sei=Nishimura en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FukadaFumi en-aut-sei=Fukada en-aut-mei=Fumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NiuQingfeng en-aut-sei=Niu en-aut-mei=Qingfeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ShimizuMotoki en-aut-sei=Shimizu en-aut-mei=Motoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YoshidaKentaro en-aut-sei=Yoshida en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TerauchiRyohei en-aut-sei=Terauchi en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ShimamotoKo en-aut-sei=Shimamoto en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KawanoYoji en-aut-sei=Kawano en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences kn-affil= affil-num=2 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=College of Agronomy, Jiangxi Agricultural University kn-affil= affil-num=4 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=5 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=6 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=7 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=8 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=9 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=10 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=11 en-affil=Faculty of Science, Kyushu University kn-affil= affil-num=12 en-affil=Department of Bioinformatics, Ritsumeikan University kn-affil= affil-num=13 en-affil=YANMAR HOLDINGS Co., Ltd. kn-affil= affil-num=14 en-affil=College of Pharmaceutical Sciences, Ritsumeikan University kn-affil= affil-num=15 en-affil=Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences kn-affil= affil-num=16 en-affil=Graduate School of Engineering Science, Yokohama National University kn-affil= affil-num=17 en-affil=Arizona Genomics Institute, School of Plant Sciences, University of Arizona kn-affil= affil-num=18 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=19 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=20 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=21 en-affil=Advanced Academy, Anhui Agricultural University, Research Centre for Biological Breeding Technology kn-affil= affil-num=22 en-affil=Iwate Biotechnology Research Center kn-affil= affil-num=23 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=24 en-affil=Iwate Biotechnology Research Center kn-affil= affil-num=25 en-affil=Laboratory of Plant Molecular Genetics, Nara Institute of Science and Technology kn-affil= affil-num=26 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=28 article-no= start-page=5739 end-page=5747 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Total synthesis and structure?antifouling activity relationship of scabrolide F en-subtitle= kn-subtitle= en-abstract= kn-abstract=An efficient synthetic strategy for scabrolide F (7), a norcembranolide diterpene that was isolated from the Taiwanese soft coral Sinularia scabra, has only recently been reported by our group. Herein, we report details of the first total synthesis of 7. The tetrahydrofuran domain of 7 was stereoselectively constructed via the 5-endo-tet cyclization of a hydroxy vinyl epoxide. The reaction of alkyl iodide 30 with dithiane 38, followed by the introduction of an alkene moiety, afforded allylation precursor 41. The coupling of alkyl iodide 42 and allylic stannane 43 was examined as a model experiment of allylation. Because the desired allylated product 44 was not obtained, an alternative synthetic route toward 7 was investigated instead. In the second synthetic approach, fragment?coupling between alkyl iodide 56 and aldehyde 58, macrolactonization, and transannular ring-closing metathesis were used as the key steps to achieve the first total synthesis of 7. We hope that this synthetic strategy provides access to the total synthesis of other macrocyclic norcembranolides. We also evaluated the antifouling activity and toxicity of 7 and its synthetic intermediates toward the cypris larvae of the barnacle Amphibalanus amphitrite. This study is the first to report the antifouling activity of norcembranolides as well as the biological activity of 7. en-copyright= kn-copyright= en-aut-name=TakamuraHiroyoshi en-aut-sei=Takamura en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugitaniYuki en-aut-sei=Sugitani en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorishitaRyohei en-aut-sei=Morishita en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YorisueTakefumi en-aut-sei=Yorisue en-aut-mei=Takefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KadotaIsao en-aut-sei=Kadota en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Institute of Natural and Environmental Sciences, University of Hyogo kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=10 article-no= start-page=5825 end-page=5840 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240425 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The ABCF proteins in Escherichia coli individually cope with 'hard-to-translate' nascent peptide sequences en-subtitle= kn-subtitle= en-abstract= kn-abstract=Organisms possess a wide variety of proteins with diverse amino acid sequences, and their synthesis relies on the ribosome. Empirical observations have led to the misconception that ribosomes are robust protein factories, but in reality, they have several weaknesses. For instance, ribosomes stall during the translation of the proline-rich sequences, but the elongation factor EF-P assists in synthesizing proteins containing the poly-proline sequences. Thus, living organisms have evolved to expand the translation capability of ribosomes through the acquisition of translation elongation factors. In this study, we have revealed that Escherichia coli ATP-Binding Cassette family-F (ABCF) proteins, YheS, YbiT, EttA and Uup, individually cope with various problematic nascent peptide sequences within the exit tunnel. The correspondence between noncanonical translations and ABCFs was YheS for the translational arrest by nascent SecM, YbiT for poly-basic sequence-dependent stalling and poly-acidic sequence-dependent intrinsic ribosome destabilization (IRD), EttA for IRD at the early stage of elongation, and Uup for poly-proline-dependent stalling. Our results suggest that ATP hydrolysis-coupled structural rearrangement and the interdomain linker sequence are pivotal for handling 'hard-to-translate' nascent peptides. Our study highlights a new aspect of ABCF proteins to reduce the potential risks that are encoded within the nascent peptide sequences. Graphical Abstract en-copyright= kn-copyright= en-aut-name=ChadaniYuhei en-aut-sei=Chadani en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamanouchiShun en-aut-sei=Yamanouchi en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UemuraEri en-aut-sei=Uemura en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiKohei en-aut-sei=Yamasaki en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NiwaTatsuya en-aut-sei=Niwa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkedaToma en-aut-sei=Ikeda en-aut-mei=Toma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KuriharaMiku en-aut-sei=Kurihara en-aut-mei=Miku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwasakiWataru en-aut-sei=Iwasaki en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TaguchiHideki en-aut-sei=Taguchi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Biological Sciences, Graduate School of Science, the University of Tokyo kn-affil= affil-num=3 en-affil=Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology kn-affil= affil-num=4 en-affil=Faculty of Science, Okayama University kn-affil= affil-num=5 en-affil=Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology kn-affil= affil-num=6 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=7 en-affil=School of Life Science and Technology, Tokyo Institute of Technology kn-affil= affil-num=8 en-affil=Department of Biological Sciences, Graduate School of Science, the University of Tokyo kn-affil= affil-num=9 en-affil=Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology kn-affil= END start-ver=1.4 cd-journal=joma no-vol=136 cd-vols= no-issue=4 article-no= start-page=94 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=FLOURY ENDOSPERM 6 mutations enhance the sugary phenotype caused by the loss of ISOAMYLASE1 in barley en-subtitle= kn-subtitle= en-abstract= kn-abstract=Starch is a biologically and commercially important glucose polymer synthesized by plants as semicrystalline starch granules (SGs). Because SG morphology affects starch properties, mutants with altered SG morphology may be useful in breeding crops with desirable starch properties, including potentially novel properties. In this study, we employed a simple screen for mutants with altered SG morphology in barley (Hordeum vulgare). We isolated mutants that formed compound SGs together with the normal simple SGs in the endosperm and found that they were allelic mutants of the starch biosynthesis genes ISOAMYLASE1 (HvISA1) and FLOURY ENDOSPERM 6 (HvFLO6), encoding starch debranching enzyme and CARBOHYDRATE-BINDING MODULE 48-containing protein, respectively. We generated the hvflo6 hvisa1 double mutant and showed that it had significantly reduced starch biosynthesis and developed shrunken grains. In contrast to starch, soluble α-glucan, phytoglycogen, and sugars accumulated to higher levels in the double mutant than in the single mutants. In addition, the double mutants showed defects in SG morphology in the endosperm and in the pollen. This novel genetic interaction suggests that hvflo6 acts as an enhancer of the sugary phenotype caused by hvisa1 mutation. en-copyright= kn-copyright= en-aut-name=MatsushimaRyo en-aut-sei=Matsushima en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisanoHiroshi en-aut-sei=Hisano en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GalisIvan en-aut-sei=Galis en-aut-mei=Ivan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiuraSatoko en-aut-sei=Miura en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CroftsNaoko en-aut-sei=Crofts en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakenakaYuto en-aut-sei=Takenaka en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OitomeNaoko F. en-aut-sei=Oitome en-aut-mei=Naoko F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshimizuTakeshi en-aut-sei=Ishimizu en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujitaNaoko en-aut-sei=Fujita en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoKazuhiro en-aut-sei=Sato en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=5 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=6 en-affil=College of Life Sciences, Ritsumeikan University kn-affil= affil-num=7 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=8 en-affil=College of Life Sciences, Ritsumeikan University kn-affil= affil-num=9 en-affil=Department of Biological Production, Akita Prefectural University kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=185 end-page=191 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reduced Immunogenicity of COVID-19 Vaccine in Obese Patients with Type 2 Diabetes: A Cross-Sectional Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The global pandemic of coronavirus infection 2019 (COVID-19) was an unprecedented public health emergency. Several clinical studies reported that heart disease, lung disease, diabetes, hypertension, dyslipidemia, and obesity are critical risk factors for increased severity of and hospitalization for COVID-19. This is largely because patients with these underlying medical conditions can show poor immune responses to the COVID-19 vaccinations. Diabetes is one of the underlying conditions most highly associated with COVID-19 susceptibility and is considered a predictor of poor prognosis of COVID-19. We therefore investigated factors that influence the anti-SARS-CoV-2 spike IgG antibody titer after three doses of vaccination in patients with type 2 diabetes. We found that obesity was associated with low anti-SARS-CoV-2 spike IgG antibody titers following three-dose vaccination in type 2 diabetics. Obese patients with type 2 diabetes may have attenuated vaccine efficacy and require additional vaccination; continuous infection control should be considered in such patients. en-copyright= kn-copyright= en-aut-name=TakahashiHiroko en-aut-sei=Takahashi en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=WatanabeMayu en-aut-sei=Watanabe en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University 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= en-keyword=obesity kn-keyword=obesity en-keyword=type 2 diabetes kn-keyword=type 2 diabetes en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=vaccination kn-keyword=vaccination END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=151 end-page=161 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors’ growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors. en-copyright= kn-copyright= en-aut-name=KomatsubaraTadashi en-aut-sei=Komatsubara en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=OmoriToshinori en-aut-sei=Omori en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugiuKazuhisa en-aut-sei=Sugiu en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MochizukiYusuke en-aut-sei=Mochizuki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DemiyaKoji en-aut-sei=Demiya en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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 Gastroenterological 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= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Oncolys BioPharma, Inc. kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=soft-tissue sarcoma kn-keyword=soft-tissue sarcoma en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=p53 kn-keyword=p53 en-keyword=BCL-xL kn-keyword=BCL-xL END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=2 article-no= start-page=123 end-page=134 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sigle Agent of Posttransplant Cyclophosphamide Without Calcineurin Inhibitor Controls Severity of Experimental Chronic GVHD en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HCT), but its pathogenesis remains unclear. Recently, haplo-identical HCT with post-transplant cyclophosphamide (Haplo-HCT with PTCY) was found to achieve a low incidence rate of acute GVHD and chronic GVHD. However, while the pathogenesis of acute GVHD following Haplo-HCT with PTCY has been well investigated, that of chronic GVHD remains to be elucidated, especially in HLA-matched HCT with PTCY. Based on its safety profile, PTCY is currently applied for the human leucocyte antigen (HLA)-matched HCT setting. Here, we investigated the mechanisms of chronic GVHD following HLA-matched HCT with PTCY using a well-defined mouse chronic GVHD model. PTCY attenuated clinical and pathological chronic GVHD by suppressing effector T-cells and preserving regulatory T-cells compared with a control group. Additionally, we demonstrated that cyclosporine A (CsA) did not show any additional positive effects on attenuation of GVHD in PTCY-treated recipients. These results suggest that monotherapy with PTCY without CsA could be a promising strategy for the prevention of chronic GVHD following HLA-matched HCT. en-copyright= kn-copyright= en-aut-name=SaekiKyosuke en-aut-sei=Saeki en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuroiTaiga en-aut-sei=Kuroi en-aut-mei=Taiga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Division of Transfusion, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=GVHD kn-keyword=GVHD en-keyword=posttransplant cyclophosphamide kn-keyword=posttransplant cyclophosphamide en-keyword=hematopoietic cell transplantation kn-keyword=hematopoietic cell transplantation en-keyword=HLA-identical kn-keyword=HLA-identical END start-ver=1.4 cd-journal=joma no-vol=290 cd-vols= no-issue=2000 article-no= start-page=20230549 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230614 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diacamma ants adjust liquid foraging strategies in response to biophysical constraints en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ant foragers provide food to the rest of the colony, often requiring transport over long distances. Foraging for liquid is challenging because it is difficult to transport and share. Many social insects store liquids inside the crop to transport them to the nest, and then regurgitate to distribute to nest-mates through a behaviour called trophallaxis. Some ants instead transport fluids with a riskier behaviour called pseudotrophallaxis?holding a drop of liquid between the mandibles through surface tension. Ants share this droplet with nest-mates without ingestion or regurgitation. We hypothesised that ants optimize their liquid-collection approach depending on viscosity. Using an ant that employs both trophallaxis and pseudotrophallaxis, we investigated the conditions where each liquid-collection behaviour is favoured by measuring biophysical properties, collection time and reaction to food quality for typical and viscosity-altered sucrose solutions. We found that ants collected more liquid per unit time by mandibular grabbing than by drinking. At high viscosities ants switched liquid collection method to mandibular grabbing in response to viscosity and not to sweetness. Our results demonstrate that ants change transport and sharing methods according to viscosity?a natural proxy for sugar concentration?thus increasing the mass of sugar returned to the nest per trip. en-copyright= kn-copyright= en-aut-name=FujiokaHaruna en-aut-sei=Fujioka en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MarchandManon en-aut-sei=Marchand en-aut-mei=Manon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LeBoeufAdria C. en-aut-sei=LeBoeuf en-aut-mei=Adria C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Physics, University of Fribourg kn-affil= affil-num=3 en-affil=Department of Biology, University of Fribourg kn-affil= en-keyword=mandibular pseudotrophallaxis kn-keyword=mandibular pseudotrophallaxis en-keyword=social bucket kn-keyword=social bucket en-keyword=liquid transportation kn-keyword=liquid transportation en-keyword=liquid collection kn-keyword=liquid collection en-keyword=optimal foraging theory kn-keyword=optimal foraging theory en-keyword=biophysics kn-keyword=biophysics END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=rbac088 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fabrication of initial trabecular bone-inspired three-dimensional structure with cell membrane nano fragments en-subtitle= kn-subtitle= en-abstract= kn-abstract=The extracellular matrix of trabecular bone has a large surface exposed to the bone marrow and plays important roles such as hematopoietic stem cell niche formation and maintenance. In vitro reproduction of trabecular bone microenvironment would be valuable not only for developing a functional scaffold for bone marrow tissue engineering but also for understanding its biological functions. Herein, we analyzed and reproduced the initial stages of trabecular bone formation in mouse femur epiphysis. We identified that the trabecular bone formation progressed through the following steps: (i) partial rupture of hypertrophic chondrocytes; (ii) calcospherite formation on cell membrane nano fragments (CNFs) derived from the ruptured cells; and (iii) calcospherite growth and fusion to form the initial three-dimensional (3D) structure of trabecular bones. For reproducing the initial trabecular bone formation in vitro, we collected CNFs from cultured cells and used as nucleation sites for biomimetic calcospherite formation. Strikingly, almost the same 3D structure of the initial trabecular bone could be obtained in vitro by using additional CNFs as a binder to fuse biomimetic calcospherites. en-copyright= kn-copyright= en-aut-name=KadoyaKoichi en-aut-sei=Kadoya en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaraEmilio Satoshi en-aut-sei=Hara en-aut-mei=Emilio Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkadaMasahiro en-aut-sei=Okada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=JiaoYu Yang en-aut-sei=Jiao en-aut-mei=Yu Yang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoTakayoshi en-aut-sei=Nakano en-aut-mei=Takayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SasakiAkira en-aut-sei=Sasaki en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto 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 Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Division of Materials & Manufacturing Science, Osaka University kn-affil= affil-num=6 en-affil=Department of Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=trabecular bone kn-keyword=trabecular bone en-keyword=calcospherites kn-keyword=calcospherites en-keyword=cell membrane nano fragments kn-keyword=cell membrane nano fragments en-keyword=three dimensionalization kn-keyword=three dimensionalization en-keyword=bone tissue synthesis kn-keyword=bone tissue synthesis END start-ver=1.4 cd-journal=joma no-vol=299 cd-vols= no-issue=8 article-no= start-page=105020 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mammalian type opsin 5 preferentially activates G14 in Gq-type G proteins triggering intracellular calcium response en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mammalian type opsin 5 (Opn5m), a UV-sensitive G protein-coupled receptor opsin highly conserved in vertebrates, would provide a common basis for UV sensing from lamprey to humans. However, G protein coupled with Opn5m remains controversial due to variations in assay conditions and the origin of Opn5m across different reports. Here, we examined Opn5m from diverse species using an aequorin luminescence assay and G alpha-KO cell line. Beyond the commonly studied major G alpha classes, G alpha q, G alpha 11, G alpha 14, and G alpha 15 in the Gq class were individually investigated in this study, as they can drive distinct signaling pathways in addition to a canonical calcium response. UV light triggered a calcium response via all the tested Opn5m proteins in 293T cells, which was abolished by Gq-type G alpha deletion and rescued by cotransfection with mouse and medaka Gq-type G alpha proteins. Opn5m preferentially activated G alpha 14 and close relatives. Mutational analysis implicated specific regions, including alpha 3-beta 5 and alpha G-alpha 4 loops, alpha G and alpha 4 helices, and the extreme C terminus, in the preferential activation of G alpha 14 by Opn5m. FISH revealed co-expression of genes encoding Opn5m and G alpha 14 in the scleral cartilage of medaka and chicken eyes, supporting their physiological coupling. This suggests that the preferential activation of G alpha 14 by Opn5m is relevant for UV sensing in specific cell types. en-copyright= kn-copyright= en-aut-name=SatoKeita en-aut-sei=Sato en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamashitaTakahiro en-aut-sei=Yamashita en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biophysics, Graduate School of Science, Kyoto University kn-affil= affil-num=3 en-affil=Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=G protein kn-keyword=G protein en-keyword=G protein?coupled receptor (GPCR) kn-keyword=G protein?coupled receptor (GPCR) en-keyword=photoreceptor kn-keyword=photoreceptor en-keyword=rhodopsin kn-keyword=rhodopsin en-keyword=calcium intracellular release kn-keyword=calcium intracellular release en-keyword=protein?protein interaction kn-keyword=protein?protein interaction en-keyword=signal transduction kn-keyword=signal transduction en-keyword=nonvisual photoreception kn-keyword=nonvisual photoreception END start-ver=1.4 cd-journal=joma no-vol=299 cd-vols= no-issue=7 article-no= start-page=104839 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural insights into the action mechanisms of artificial electron acceptors in photosystem II en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosystem II (PSII) utilizes light energy to split water, and the electrons extracted from water are transferred to QB, a plastoquinone molecule bound to the D1 subunit of PSII. Many artificial electron acceptors (AEAs) with molecular structures similar to that of plastoquinone can accept electrons from PSII. However, the molecular mechanism by which AEAs act on PSII is unclear. Here, we solved the crystal structure of PSII treated with three different AEAs, 2,5-dibromo-1,4-benzoquinone, 2,6dichloro-1,4-benzoquinone, and 2-phenyl-1,4-benzoquinone, at 1.95 to 2.10 angstrom resolution. Our results show that all AEAs substitute for QB and are bound to the QB-binding site (QB site) to receive electrons, but their binding strengths are different, resulting in differences in their efficiencies to accept electrons. The acceptor 2-phenyl-1,4-benzoquinone binds most weakly to the QB site and showed the highest oxygen-evolving activity, implying a reverse relationship between the binding strength and oxygen-evolving activity. In addition, a novel quinonebinding site, designated the QD site, was discovered, which is located in the vicinity of QB site and close to QC site, a binding site reported previously. This QD site is expected to play a role as a channel or a storage site for quinones to be transported to the QB site. These results provide the structural basis for elucidating the actions of AEAs and exchange mechanism of QB in PSII and also provide information for the design of more efficient electron acceptors. en-copyright= kn-copyright= en-aut-name=KamadaShinji en-aut-sei=Kamada en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= affil-num=1 en-affil=Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Photosystem II kn-keyword=Photosystem II en-keyword=photosynthesis kn-keyword=photosynthesis en-keyword=electron transfer kn-keyword=electron transfer en-keyword=structural biology kn-keyword=structural biology en-keyword=crystal structure kn-keyword=crystal structure en-keyword=electron acceptor kn-keyword=electron acceptor END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=1 article-no= start-page=43 end-page=48 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Preliminary Study of Dental Caries Detection by Deep Neural Network Applying Domain-Specific Transfer Learning en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose The purpose of this study is to confirm whether it is possible to acquire a certain degree of diagnostic ability even with a small dataset using domain-specific transfer learning. In this study, we constructed a simulated caries detection model on panoramic tomography using transfer learning.
Methods A simulated caries model was trained and validated using 1094 trimmed intraoral images. A convolutional neural network (CNN) with three convolution and three max pooling layers was developed. We applied this caries detection model to 50 panoramic images and evaluated its diagnostic performance.
Results The diagnostic performance of the CNN model on the intraoral film was as follows: C0 84.6%; C1 90.6%; C2 88.6%. Finally, we tested 50 panoramic images with simulated caries insertion. The diagnostic performance of the CNN model on the panoramic image was as follows: C0 75.0%, C1 80.0%, C2 80.0%, and overall diagnostic accuracy was 78.0%. The diagnostic performance of the caries detection model constructed only with panoramic images was much lower than that of the intraoral film.
Conclusion Domain-specific transfer learning methods may be useful for saving datasets and training time (179/250). en-copyright= kn-copyright= en-aut-name=KawazuToshiyuki en-aut-sei=Kawazu en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujikuraMamiko en-aut-sei=Fujikura en-aut-mei=Mamiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkadaShunsuke en-aut-sei=Okada en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HisatomiMiki en-aut-sei=Hisatomi en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsaumiJunichi en-aut-sei=Asaumi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Diagnosis and Dentomaxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Oral Diagnosis and Dentomaxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Oral Diagnosis and Dentomaxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Deep neural networks kn-keyword=Deep neural networks en-keyword=Caries detection kn-keyword=Caries detection en-keyword=Domain-Specific transfer learning kn-keyword=Domain-Specific transfer learning en-keyword=Panoramic tomography kn-keyword=Panoramic tomography END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue= article-no= start-page=1338669 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tetrathionate hydrolase from the acidophilic microorganisms en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tetrathionate hydrolase (TTH) is a unique enzyme found in acidophilic sulfur-oxidizing microorganisms, such as bacteria and archaea. This enzyme catalyzes the hydrolysis of tetrathionate to thiosulfate, elemental sulfur, and sulfate. It is also involved in dissimilatory sulfur oxidation metabolism, the S-4-intermediate pathway. TTHs have been purified and characterized from acidophilic autotrophic sulfur-oxidizing microorganisms. All purified TTHs show an optimum pH in the acidic range, suggesting that they are localized in the periplasmic space or outer membrane. In particular, the gene encoding TTH from Acidithiobacillus ferrooxidans (Af-tth) was identified and recombinantly expressed in Escherichia coli cells. TTH activity could be recovered from the recombinant inclusion bodies by acid refolding treatment for crystallization. The mechanism of tetrathionate hydrolysis was then elucidated by X-ray crystal structure analysis. Af-tth is highly expressed in tetrathionate-grown cells but not in iron-grown cells. These unique structural properties, reaction mechanisms, gene expression, and regulatory mechanisms are discussed in this review. en-copyright= kn-copyright= en-aut-name=KanaoTadayoshi en-aut-sei=Kanao en-aut-mei=Tadayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Agricultural and Biological Chemistry, Graduate School of Environment, Life, Natural Science, and Technology, Okayama University kn-affil= en-keyword=tetrathionate hydrolase kn-keyword=tetrathionate hydrolase en-keyword=reduced inorganic sulfur compounds kn-keyword=reduced inorganic sulfur compounds en-keyword=dissimilatory sulfur metabolism kn-keyword=dissimilatory sulfur metabolism en-keyword=S4-intermediate pathway kn-keyword=S4-intermediate pathway en-keyword=acidophiles kn-keyword=acidophiles en-keyword=chemoautotroph kn-keyword=chemoautotroph END start-ver=1.4 cd-journal=joma no-vol=113 cd-vols= no-issue= article-no= start-page=41 end-page=48 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Instant estimation of rice yield using ground-based RGB images and its potential applicability to UAV en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rice (Oryza sativa L.) is one of the most important cereals, which provides 20% of the world’s food energy. However, its productivity is poorly assessed especially in the global South. Here, we provide a first study to perform a deep learning-based approach for instantaneously estimating rice yield using RGB images. During ripening stage and at harvest, over 22,000 digital images were captured vertically downwards over the rice canopy from a distance of 0.8 to 0.9m at 4,820 harvesting plots having the yield of 0.1 to 16.1 t ha-1 across six countries in Africa and Japan. A convolutional neural network (CNN) applied to these data at harvest predicted 68% variation in yield with a relative root mean square error (rRMSE) of 0.22. Even when the resolution of images was reduced (from 0.2 to 3.2cm pixel-1 of ground sampling distance), the model could predict 57% variation in yield, implying that this approach can be scaled by use of unmanned aerial vehicles. Our work offers low-cost, hands-on, and rapid approach for high throughput phenotyping, and can lead to impact assessment of productivity-enhancing interventions, detection of fields where these are needed to sustainably increase crop production. en-copyright= kn-copyright= en-aut-name=TanakaYu en-aut-sei=Tanaka en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeTomoya en-aut-sei=Watanabe en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsuraKeisuke en-aut-sei=Katsura en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujimotoYasuhiro en-aut-sei=Tsujimoto en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakaiToshiyuki en-aut-sei=Takai en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaTakashi Sonam Tashi en-aut-sei=Tanaka en-aut-mei=Takashi Sonam Tashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawamuraKensuke en-aut-sei=Kawamura en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SaitoHiroki en-aut-sei=Saito en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HommaKoki en-aut-sei=Homma en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MairouaSalifou Goube en-aut-sei=Mairoua en-aut-mei=Salifou Goube kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AhouantonKokou en-aut-sei=Ahouanton en-aut-mei=Kokou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IbrahimAli en-aut-sei=Ibrahim en-aut-mei=Ali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SenthilkumarKalimuthu en-aut-sei=Senthilkumar en-aut-mei=Kalimuthu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SemwalVimal Kumar en-aut-sei=Semwal en-aut-mei=Vimal Kumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MatuteEduardo Jose Graterol en-aut-sei=Matute en-aut-mei=Eduardo Jose Graterol kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=CorredorEdgar en-aut-sei=Corredor en-aut-mei=Edgar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=El-NamakyRaafat en-aut-sei=El-Namaky en-aut-mei=Raafat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ManigbasNorvie en-aut-sei=Manigbas en-aut-mei=Norvie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=QuilangEduardo Jimmy P. en-aut-sei=Quilang en-aut-mei=Eduardo Jimmy P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=IwahashiYu en-aut-sei=Iwahashi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NakajimaKota en-aut-sei=Nakajima en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=TakeuchiEisuke en-aut-sei=Takeuchi en-aut-mei=Eisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SaitoKazuki en-aut-sei=Saito en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Mathematics, Kyushu University kn-affil= affil-num=3 en-affil=Graduate School of Agriculture, Tokyo University of Agriculture and Technology kn-affil= affil-num=4 en-affil=Japan International Research Center for Agricultural Sciences kn-affil= affil-num=5 en-affil=Japan International Research Center for Agricultural Sciences kn-affil= affil-num=6 en-affil=Faculty of Biological Sciences, Gifu UniversityFaculty of Biological Sciences, Gifu University kn-affil= affil-num=7 en-affil=Japan International Research Center for Agricultural Sciences kn-affil= affil-num=8 en-affil=Tropical Agriculture Research Front, Japan International Research Center for Agricultural Sciences kn-affil= affil-num=9 en-affil=Graduate School of Agricultural Science, Tohoku University kn-affil= affil-num=10 en-affil=Africa Rice Center （AfricaRice） kn-affil= affil-num=11 en-affil=Africa Rice Center （AfricaRice） kn-affil= affil-num=12 en-affil=Africa Rice Center （AfricaRice）, Regional Station for the Sahel kn-affil= affil-num=13 en-affil=Africa Rice Center （AfricaRice） kn-affil= affil-num=14 en-affil=Africa Rice Center （AfricaRice）, Nigeria Station kn-affil= affil-num=15 en-affil=Latin American Fund for Irrigated Rice - The Alliance of Bioversity International and CIAT kn-affil= affil-num=16 en-affil=Latin American Fund for Irrigated Rice - The Alliance of Bioversity International and CIAT kn-affil= affil-num=17 en-affil=Rice Research and Training Center, Field Crops Research Institute kn-affil= affil-num=18 en-affil=Philippine Rice Research Institute （PhilRice） kn-affil= affil-num=19 en-affil=Philippine Rice Research Institute （PhilRice） kn-affil= affil-num=20 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=21 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=22 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=23 en-affil=Japan International Research Center for Agricultural Sciences kn-affil= en-keyword=Rice (Oryza sativa L.) kn-keyword=Rice (Oryza sativa L.) en-keyword=rough grain yield kn-keyword=rough grain yield en-keyword=convolutional neural network kn-keyword=convolutional neural network en-keyword=RGB images kn-keyword=RGB images en-keyword=UAV kn-keyword=UAV END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=2 article-no= start-page=532 end-page=542 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231229 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=pSPICA Force Field Extended for Proteins and Peptides en-subtitle= kn-subtitle= en-abstract= kn-abstract=Many coarse-grained (CG) molecular dynamics (MD) studies have been performed to investigate biological processes involving proteins and lipids. CG force fields (FFs) in these MD studies often use implicit or nonpolar water models to reduce computational costs. CG-MD using water models cannot properly describe electrostatic screening effects owing to the hydration of ionic segments and thus cannot appropriately describe molecular events involving water channels and pores through lipid membranes. To overcome this issue, we developed a protein model in the pSPICA FF, in which a polar CG water model showing the proper dielectric response was adopted. The developed CG model greatly improved the transfer free energy profiles of charged side chain analogues across the lipid membrane. Application studies on melittin-induced membrane pores and mechanosensitive channels in lipid membranes demonstrated that CG-MDs using the pSPICA FF correctly reproduced the structure and stability of the pores and channels. Furthermore, the adsorption behavior of the highly charged nona-arginine peptides on lipid membranes changed with salt concentration, indicating the pSPICA FF is also useful for simulating protein adsorption on membrane surfaces. en-copyright= kn-copyright= en-aut-name=MiyazakiYusuke en-aut-sei=Miyazaki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShinodaWataru en-aut-sei=Shinoda en-aut-mei=Wataru 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=Research Institute for Interdisciplinary Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=42 cd-vols= no-issue=12 article-no= start-page=113569 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231226 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mechanistic dissection of premature translation termination induced by acidic residues-enriched nascent peptide en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ribosomes polymerize nascent peptides through repeated inter-subunit rearrangements between the classic and hybrid states. The peptidyl-tRNA, the intermediate species during translation elongation, stabi-lizes the translating ribosome to ensure robust continuity of elongation. However, the translation of acidic residue-rich sequences destabilizes the ribosome, leading to a stochastic premature translation cessation termed intrinsic ribosome destabilization (IRD), which is still ill-defined. Here, we dissect the molecular mechanisms underlying IRD in Escherichia coli. Reconstitution of the IRD event reveals that (1) the prolonged ribosome stalling enhances IRD-mediated translation discontinuation, (2) IRD depends on temperature, (3) the destabilized 70S ribosome complex is not necessarily split, and (4) the destabilized ribosome is subjected to peptidyl-tRNA hydrolase-mediated hydrolysis of the peptidyl-tRNA without subunit splitting or recycling factors-mediated subunit splitting. Collectively, our data indicate that the translation of acidic-rich sequences alters the conformation of the 70S ribosome to an aberrant state that allows the noncanonical pre-mature termination. en-copyright= kn-copyright= en-aut-name=ChadaniYuhei en-aut-sei=Chadani en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanamoriTakashi en-aut-sei=Kanamori en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NiwaTatsuya en-aut-sei=Niwa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IchiharaKazuya en-aut-sei=Ichihara en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakayamaKeiichi I. en-aut-sei=Nakayama en-aut-mei=Keiichi I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoAkinobu en-aut-sei=Matsumoto en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaguchiHideki en-aut-sei=Taguchi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=GeneFrontier Corporation kn-affil= affil-num=3 en-affil=Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology kn-affil= affil-num=4 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=5 en-affil=Anticancer Strategies Laboratory, TMDU Advanced Research Institute, Tokyo Medical and Dental University kn-affil= affil-num=6 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=7 en-affil=Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology kn-affil= END start-ver=1.4 cd-journal=joma no-vol=59 cd-vols= no-issue= article-no= start-page=439 end-page=445 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Solid-state inorganic and metallic adhesives for soft biological tissues en-subtitle= kn-subtitle= en-abstract= kn-abstract=Currently, the soft-tissue adhesives used in clinical practice are glue-type organic adhesives. However, there is a demand for new types of adhesives, because the current organic adhesives present challenges in terms of their biocompatibility and adhesion strength. This review summarizes the discovery and development of inorganic and metallic adhesives designed for soft biological tissues while focusing on immobilization of medical divices on soft tissues. These new types of adhesives are in a solid state and adhere directly and immediately to soft tissues. Therefore, they are called "solid-state adhesives" to distinguish them from the currently used glue-type adhesives. In previous studies on inorganic solid-state adhesives, oxides and calcium phosphates were used as raw materials in the form of nanoparticles, nanoparticle-coated films, or nanoparticle-assembled porous plates. In previous studies on metallic solid-state adhesives, only Ti and its alloys were used as raw materials. This review also discusses the future perspectives in this active research area. en-copyright= kn-copyright= en-aut-name=OkadaMasahiro en-aut-sei=Okada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Soft-tissue adhesive kn-keyword=Soft-tissue adhesive en-keyword=Solid-state adhesion kn-keyword=Solid-state adhesion en-keyword=Oxide kn-keyword=Oxide en-keyword=Calcium phosphate kn-keyword=Calcium phosphate en-keyword=Titanium kn-keyword=Titanium END start-ver=1.4 cd-journal=joma no-vol=180 cd-vols= no-issue= article-no= start-page=112270 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202309 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Attenuation of pulmonary damage in aged lipopolysaccharide-induced inflammation mice through continuous 2?% hydrogen gas inhalation: A potential therapeutic strategy for geriatric inflammation and survival en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: With the global population aging, there is an increased prevalence of sepsis among the elderly, a demographic particularly susceptible to inflammation. This study aimed to evaluate the therapeutic potential of hydrogen gas, known for its anti-inflammatory and antioxidant properties, in attenuating inflammation specifically in the lungs and liver, and age-associated molecular markers in aged mice.
Methods: Male mice aged 21 to 23 months, representative of the human elderly population, were subjected to inflammation via intraperitoneal injection of lipopolysaccharide (LPS). The mice were allocated into eight groups to examine the effects of varying durations and concentrations of hydrogen gas inhalation: control, saline without hydrogen, saline with 24-hour 2 % hydrogen, LPS without hydrogen, LPS with 24-hour 2 % hydrogen, LPS with 6-hour 2 % hydrogen, LPS with 1-hour 2 % hydrogen, and LPS with 24-hour 1 % hydrogen. Parameters assessed included survival rate, activity level, inflammatory biomarkers, and organ injury.
Results: Extended administration of hydrogen gas specifically at a 2 % concentration for 24 h led to a favorable prognosis in the aged mice by reducing mRNA expression of inflammatory biomarkers in lung and liver tissue, mitigating lung injury, and diminishing the expression of the senescence-associated protein p21. Moreover, hydrogen gas inhalation selectively ameliorated senescence-related markers in lung tissue, including C-X-C motif chemokine 2, metalloproteinase-3, and arginase-1. Notably, hydrogen gas did not alleviate LPS-induced liver injury under the conditions tested.
Conclusion: The study highlights that continuous inhalation of hydrogen gas at a 2 % concentration for 24 h can be a potent intervention in the geriatric population for improving survival and physical activity by mitigating pulmonary inflammation and modulating senescence-related markers in aged mice with LPS-induced inflammation. This finding paves the way for future research into hydrogen gas as a therapeutic strategy to alleviate severe inflammation that can lead to organ damage in the elderly. en-copyright= kn-copyright= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IketaniMasumi en-aut-sei=Iketani en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SeyaMizuki en-aut-sei=Seya en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MengYing en-aut-sei=Meng en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AgetaKohei en-aut-sei=Ageta en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhsawaIkuroh en-aut-sei=Ohsawa en-aut-mei=Ikuroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= en-keyword=LPS-induced inflammation kn-keyword=LPS-induced inflammation en-keyword=Elderly sepsis kn-keyword=Elderly sepsis en-keyword=Lipopolysaccharide kn-keyword=Lipopolysaccharide en-keyword=Aged mouse kn-keyword=Aged mouse en-keyword=Senescence-related markers kn-keyword=Senescence-related markers en-keyword=Molecular hydrogen kn-keyword=Molecular hydrogen en-keyword=Hydrogen gas inhalation kn-keyword=Hydrogen gas inhalation END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=7 article-no= start-page=100873 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of liquefied sake lees on growth performance and faecal and blood characteristics in Japanese Black calves en-subtitle= kn-subtitle= en-abstract= kn-abstract=Liquefied sake lees, a by-product of Japanese sake, is rich in Saccharomyces cerevisiae, proteins, and prebiotics derived from rice and yeast. Previous studies have reported that Saccharomyces cerevisiae fermentation products improved the health, growth, and faecal characteristics of preweaning calves. This study investigated the effects of adding liquefied sake lees to milk replacer on the growth performance, faecal characteristics, and blood metabolites of preweaning Japanese Black calves from 6 to 90 days of age. Twenty-four Japanese Black calves at 6 days of age were randomly assigned to one of three treatments: No liquefied sake lees (C, n = 8), 100 g/d (on a fresh matter basis) liquefied sake lees mixed with milk replacer (LS, n = 8), and 200 g/d (on a fresh matter basis) liquefied sake lees mixed with milk replacer (HS, n = 8). The intake of milk replacer and calf starter, as well as, the average daily gain did not differ between the treatments. The number of days counted with faecal score 1 in LS was higher than in HS (P < 0.05), while the number of days with diarrhoea medication in LS and C was lower than HS (P < 0.05). The faecal n-butyric acid concentration tended to be higher in LS compared to C (P = 0.060). The alpha diversity index (Chao1) was higher in HS than in C and LS at 90 days of age (P < 0.05). The principal coordinate analysis (PCoA) using weighted UniFrac distance showed that the bacterial community structures in faeces among the treatments at 90 days of age were significantly different (P < 0.05). The plasma β-hydroxybutyric acid concentration, an indicator of rumen development, was higher for LS than in C throughout the experiment (P < 0.05). These results suggested that adding liquefied sake lees up to 100 g/d (on a fresh matter basis) might promote rumen development in preweaning Japanese Black calves. en-copyright= kn-copyright= en-aut-name=KatsumataS. en-aut-sei=Katsumata en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiY. en-aut-sei=Hayashi en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OishiK. en-aut-sei=Oishi en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsukaharaT. en-aut-sei=Tsukahara en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueR. en-aut-sei=Inoue en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ObataA. en-aut-sei=Obata en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HirookaH. en-aut-sei=Hirooka en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KumagaiH. en-aut-sei=Kumagai en-aut-mei=H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Shiga Prefectural Livestock Production Technology Promotion Center kn-affil= affil-num=3 en-affil=Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=4 en-affil=Kyoto Institute of Nutrition and Pathology kn-affil= affil-num=5 en-affil=Department of Applied Biological Sciences, Faculty of Agriculture, Setsunan University kn-affil= affil-num=6 en-affil=Shiga Prefectural Livestock Production Technology Promotion Center kn-affil= affil-num=7 en-affil=Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=8 en-affil=Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University kn-affil= en-keyword=By-products kn-keyword=By-products en-keyword=Faecal microbiota kn-keyword=Faecal microbiota en-keyword=Japanese Black cattle kn-keyword=Japanese Black cattle en-keyword=Preweaning calves kn-keyword=Preweaning calves en-keyword=Saccharomyces cerevisiae kn-keyword=Saccharomyces cerevisiae END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=12 article-no= start-page=1706 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of Human Endogenous Retroviruses and Endogenous Virus-Like Elements in Cancer Development and Innate Immunity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections in the host genome. Although mutations and silencing mechanisms impair their original role in viral replication, HERVs are believed to play roles in various biological processes. Long interspersed nuclear elements (LINEs) are non-LTR retrotransposons that have a lifecycle resembling that of retroviruses. Although LINE expression is typically silenced in somatic cells, it also contributes to various biological processes. The aberrant expression of HERVs and LINEs is closely associated with the development of cancer and/or immunological diseases, suggesting that they are integrated into various pathways related to the diseases. HERVs/LINEs control gene expression depending on the context as promoter/enhancer elements. Some RNAs and proteins derived from HERVs/LINEs have oncogenic potential, whereas others stimulate innate immunity. Non-retroviral endogenous viral elements (nrEVEs) are a novel type of virus-like element in the genome. nrEVEs may also be involved in host immunity. This article provides a current understanding of how these elements impact cellular physiology in cancer development and innate immunity, and provides perspectives for future studies. en-copyright= kn-copyright= en-aut-name=KatohHirokazu en-aut-sei=Katoh en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HondaTomoyuki en-aut-sei=Honda en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=HERVs kn-keyword=HERVs en-keyword=LINEs kn-keyword=LINEs en-keyword=cancer kn-keyword=cancer en-keyword=innate immunity kn-keyword=innate immunity en-keyword=promoter kn-keyword=promoter en-keyword=enhancer kn-keyword=enhancer en-keyword=interferon signaling kn-keyword=interferon signaling END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=18 article-no= start-page=2893 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230909 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MicroRNAs as Biomarkers and Therapeutic Targets for Acute Kidney Injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Acute kidney injury (AKI) is a clinical syndrome where a rapid decrease in kidney function and/or urine output is observed, which may result in the imbalance of water, electrolytes and acid base. It is associated with poor prognosis and prolonged hospitalization. Therefore, an early diagnosis and treatment to avoid the severe AKI stage are important. While several biomarkers, such as urinary L-FABP and NGAL, can be clinically useful, there is still no gold standard for the early detection of AKI and there are limited therapeutic options against AKI. miRNAs are non-coding and single-stranded RNAs that silence their target genes in the post-transcriptional process and are involved in a wide range of biological processes. Recent accumulated evidence has revealed that miRNAs may be potential biomarkers and therapeutic targets for AKI. In this review article, we summarize the current knowledge about miRNAs as promising biomarkers and potential therapeutic targets for AKI, as well as the challenges in their clinical use. en-copyright= kn-copyright= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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= en-keyword=microRNA kn-keyword=microRNA en-keyword=acute kidney injury kn-keyword=acute kidney injury en-keyword=biomarker kn-keyword=biomarker en-keyword=mesenchymal stem cell kn-keyword=mesenchymal stem cell END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=6 article-no= start-page=671 end-page=674 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dramatic Response to Tezepelumab as an Initial Biologic Agent for Refractory Asthma Associated with Type 2 and Non-type 2 Traits en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 74-year-old Japanese woman presented with a 45-year history of refractory asthma. She had been treated with inhaled corticosteroids, a long-acting β2-agonist, and a long-acting muscarinic antagonist for 6 months. She also had a repeated viral infection. Her condition had been characterized as a refractory asthma associated with type 2 and non-type 2 traits. We began treatment with tezepelumab. The control of the patient’s asthma symptoms and quality of life improved greatly within 1 month (changes in eosinophil count from 748 to 96 /μL, in FeNO from 32 to 17 ppb, in the Asthma Quality of Life Questionnaire score from 3.59 to 6.68, and in the Asthma Control Test score from 13 to 23). Tezepelumab was effective as an initial biologic agent for a patient with refractory asthma associated with type 2 and non-type 2 traits. en-copyright= kn-copyright= en-aut-name=MinamiDaisuke en-aut-sei=Minami en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HosoyaTakeshi en-aut-sei=Hosoya en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HosoyaMasaharu en-aut-sei=Hosoya en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaganoAkichika en-aut-sei=Nagano en-aut-mei=Akichika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakajimaYasuhiro en-aut-sei=Nakajima en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanehiroArihiko en-aut-sei=Kanehiro en-aut-mei=Arihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Hosoya Hospital kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Hosoya Hospital kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Hosoya Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Himeji Saint Mary’s Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Himeji Saint Mary’s Hospital kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Himeji Saint Mary’s Hospital kn-affil= affil-num=7 en-affil=Department of Internal Medicine, Himeji Saint Mary’s Hospital kn-affil= en-keyword=tezepelumab kn-keyword=tezepelumab en-keyword=biologic agent kn-keyword=biologic agent en-keyword=eosinophilic kn-keyword=eosinophilic en-keyword=non-type 2 kn-keyword=non-type 2 en-keyword=severe asthma kn-keyword=severe asthma END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=6 article-no= start-page=665 end-page=669 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Omental Abscess after Laparoscopic Proximal Gastrectomy Successfully Treated with Percutaneous Drainage en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report the case details of a 65-year-old Japanese man with an omental abscess that was discovered 43 days after he underwent a laparoscopic proximal gastrectomy for gastric cancer. His chief complaint was mild abdominal pain that had persisted for several days. The abscess was diagnosed as a rare postoperative complication. We hesitated to perform a reoperation given the invasiveness of general anesthesia and surgery, plus the possibility of postoperative adhesions and because the patient’s general condition was stable and he had only mild abdominal pain. Percutaneous drainage using a 10.2-F catheter was performed with the patient under conscious sedation and computed tomography?fluoroscopy guidance, with no complications. After the procedure, the size of the abscess cavity was remarkably reduced, and 23 days later the catheter was withdrawn. en-copyright= kn-copyright= en-aut-name=SakuraiAtsunobu en-aut-sei=Sakurai en-aut-mei=Atsunobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=9 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=drainage kn-keyword=drainage en-keyword=omental abscess kn-keyword=omental abscess en-keyword=omental infarction kn-keyword=omental infarction en-keyword=proximal gastrectomy kn-keyword=proximal gastrectomy END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=2281159 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microtubule-associated proteins WDL5 and WDL6 play a critical role in pollen tube growth in Arabidopsis thaliana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Morphological response of cells to environment involves concerted rearrangements of microtubules and actin microfilaments. A mutant of WAVE-DAMPENED2-LIKE5 (WDL5), which encodes an ethylene-regulated microtubule-associated protein belonging to the WVD2/WDL family in Arabidopsis thaliana, shows attenuation in the temporal root growth reduction in response to mechanical stress. We found that a T-DNA knockout of WDL6, the closest homolog of WDL5, oppositely shows an enhancement of the response. To know the functional relationship between WDL5 and WDL6, we attempted to generate the double mutant by crosses but failed in isolation. Close examination of gametophytes in plants that are homozygous for one and heterozygous for the other revealed that these plants produce pollen grains with a reduced rate of germination and tube growth. Reciprocal cross experiments of these plants with the wild type confirmed that the double mutation is not inherited paternally. These results suggest a critical and cooperative function of WDL5 and WDL6 in pollen tube growth. en-copyright= kn-copyright= en-aut-name=OkamotoTakashi en-aut-sei=Okamoto en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MotoseHiroyasu en-aut-sei=Motose en-aut-mei=Hiroyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiTaku en-aut-sei=Takahashi en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Biological Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Biological Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Biological Science, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Arabidopsis kn-keyword=Arabidopsis en-keyword=pollen germination kn-keyword=pollen germination en-keyword=pollen tube growth kn-keyword=pollen tube growth en-keyword=the WVD2/WDL family kn-keyword=the WVD2/WDL family END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=20 article-no= start-page=4190 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fabrication of a Fish-Bone-Inspired Inorganic-Organic Composite Membrane en-subtitle= kn-subtitle= en-abstract= kn-abstract=Biological materials have properties like great strength and flexibility that are not present in synthetic materials. Using the ribs of crucian carp as a reference, we investigated the mechanisms behind the high mechanical properties of this rib bone, and found highly oriented layers of calcium phosphate (CaP) and collagen fibers. To fabricate a fish-rib-bone-mimicking membrane with similar structure and mechanical properties, this study involves (1) the rapid synthesis of plate-like CaP crystals, (2) the layering of CaP-gelatin hydrogels by gradual drying, and (3) controlling the shape of composite membranes using porous gypsum molds. Finally, as a result of optimizing the compositional ratio of CaP filler and gelatin hydrogel, a CaP filler content of 40% provided the optimal mechanical properties of toughness and stiffness similar to fish bone. Due to the rigidity, flexibility, and ease of shape control of the composite membrane materials, this membrane could be applied as a guided bone regeneration (GBR) membrane. en-copyright= kn-copyright= en-aut-name=JiaoYuyang en-aut-sei=Jiao en-aut-mei=Yuyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkadaMasahiro en-aut-sei=Okada en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NutanBhingaradiya en-aut-sei=Nutan en-aut-mei=Bhingaradiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=BikharudinAhmad en-aut-sei=Bikharudin en-aut-mei=Ahmad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MusaRanda en-aut-sei=Musa en-aut-mei=Randa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto 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 Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=4 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=7 en-affil=Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= en-keyword=fish bone kn-keyword=fish bone en-keyword=lamellar structure kn-keyword=lamellar structure en-keyword=self-assembly kn-keyword=self-assembly en-keyword=guided bone regeneration kn-keyword=guided bone regeneration END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=054107 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231016 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Diamond quantum sensors in microfluidics technology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diamond quantum sensing is an emerging technology for probing multiple physico-chemical parameters in the nano- to micro-scale dimensions within diverse chemical and biological contexts. Integrating these sensors into microfluidic devices enables the precise quantification and analysis of small sample volumes in microscale channels. In this Perspective, we present recent advancements in the integration of diamond quantum sensors with microfluidic devices and explore their prospects with a focus on forthcoming technological developments. en-copyright= kn-copyright= en-aut-name=FujiwaraMasazumi en-aut-sei=Fujiwara en-aut-mei=Masazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=291 cd-vols= no-issue=6 article-no= start-page=1119 end-page=1130 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231020 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hepatitis C virus NS5B triggers an MDA5-mediated innate immune response by producing dsRNA without the replication of viral genomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=During the replication of viral genomes, RNA viruses produce double-stranded RNA (dsRNA), through the activity of their RNA-dependent RNA polymerases (RdRps) as viral replication intermediates. Recognition of viral dsRNA by host pattern recognition receptors ? such as retinoic acid-induced gene-I (RIG-I)-like receptors and Toll-like receptor 3 ? triggers the production of interferon (IFN)-β via the activation of IFN regulatory factor (IRF)-3. It has been proposed that, during the replication of viral genomes, each of RIG-I and melanoma differentiation-associated gene 5 (MDA5) form homodimers for the efficient activation of a downstream signalling pathway in host cells. We previously reported that, in the non-neoplastic human hepatocyte line PH5CH8, the RdRp NS5B derived from hepatitis C virus (HCV) could induce IFN-β expression by its RdRp activity without the actual replication of viral genomes. However, the exact mechanism by which HCV NS5B produced IFN-β remained unknown. In the present study, we first showed that NS5B derived from another Flaviviridae family member, GB virus B (GBV-B), also possessed the ability to induce IFN-β in PH5CH8 cells. Similarly, HCV NS5B, but not its G317V mutant, which lacks RdRp activity, induced the dimerization of MDA5 and subsequently the activation of IRF-3. Interestingly, immunofluorescence analysis showed that HCV NS5B produced dsRNA. Like HCV NS5B, GBV-B NS5B also triggered the production of dsRNA and subsequently the dimerization of MDA5. Taken together, our results show that HCV NS5B triggers an MDA5-mediated innate immune response by producing dsRNA without the replication of viral genomes in human hepatocytes. en-copyright= kn-copyright= en-aut-name=DansakoHiromichi en-aut-sei=Dansako en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AriumiYasuo en-aut-sei=Ariumi en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoNobuyuki en-aut-sei=Kato en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Biological Information Technology, Joint Research Center for Human Retrovirus Infection, Kagoshima University kn-affil= affil-num=3 en-affil=Management Department of Biosafety, Laboratory Animal, and Pathogen Bank, National Institute of Infectious Diseases kn-affil= affil-num=4 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=double-stranded RNA kn-keyword=double-stranded RNA en-keyword=hepatitis C virus kn-keyword=hepatitis C virus en-keyword=innate immunity kn-keyword=innate immunity en-keyword=RIG-I-like receptor kn-keyword=RIG-I-like receptor en-keyword=RNA virus kn-keyword=RNA virus END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=1239598 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=“Input/output cytokines” in epidermal keratinocytes and the involvement in inflammatory skin diseases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Considering the role of epidermal keratinocytes, they occupy more than 90% of the epidermis, form a physical barrier, and also function as innate immune barrier. For example, epidermal keratinocytes are capable of recognizing various cytokines and pathogen-associated molecular pattern, and producing a wide variety of inflammatory cytokines, chemokines, and antimicrobial peptides. Previous basic studies have shown that the immune response of epidermal keratinocytes has a significant impact on inflammatory skin diseases. The purpose of this review is to provide foundation of knowledge on the cytokines which are recognized or produced by epidermal keratinocytes. Since a number of biologics for skin diseases have appeared, it is necessary to fully understand the relationship between epidermal keratinocytes and the cytokines. In this review, the cytokines recognized by epidermal keratinocytes are specifically introduced as "input cytokines", and the produced cytokines as "output cytokines". Furthermore, we also refer to the existence of biologics against those input and output cytokines, and the target skin diseases. These use results demonstrate how important targeted cytokines are in real skin diseases, and enhance our understanding of the cytokines. en-copyright= kn-copyright= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MukaiTomoyuki en-aut-sei=Mukai en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SunagawaKo en-aut-sei=Sunagawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawakamiYoshio en-aut-sei=Kawakami en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=epidermal keratinocytes kn-keyword=epidermal keratinocytes en-keyword=input cytokines kn-keyword=input cytokines en-keyword=output cytokines kn-keyword=output cytokines en-keyword=biologics kn-keyword=biologics en-keyword=inflammatory skin diseases kn-keyword=inflammatory skin diseases END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=2 article-no= start-page=154 end-page=164 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of a Functionally Efficient and Thermally Stable Outward Sodium-Pumping Rhodopsin (BeNaR) from a Thermophilic Bacterium en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rhodopsins are transmembrane proteins with retinal chromophores that are involved in photo-energy conversion and photo-signal transduction in diverse organisms. In this study, we newly identified and characterized a rhodopsin from a thermophilic bacterium, Bellilinea sp. Recombinant Escherichia coli cells expressing the rhodopsin showed light-induced alkalization of the medium only in the presence of sodium ions (Na+), and the alkalization signal was enhanced by addition of a protonophore, indicating an outward Na+ pump function across the cellular membrane. Thus, we named the protein Bellilinea Na+-pumping rhodopsin, BeNaR. Of note, its Na+-pumping activity is significantly greater than that of the known Na+-pumping rhodopsin, KR2. We further characterized its photochemical properties as follows: (i) Visible spectroscopy and HPLC revealed that BeNaR has an absorption maximum at 524?nm with predominantly (>96%) the all-trans retinal conformer. (ii) Time-dependent thermal denaturation experiments revealed that BeNaR showed high thermal stability. (iii) The time-resolved flash-photolysis in the nanosecond to millisecond time domains revealed the presence of four kinetically distinctive photointermediates, K, L, M and O. (iv) Mutational analysis revealed that Asp101, which acts as a counterion, and Asp230 around the retinal were essential for the Na+-pumping activity. From the results, we propose a model for the outward Na+-pumping mechanism of BeNaR. The efficient Na+-pumping activity of BeNaR and its high stability make it a useful model both for ion transporters and optogenetics tools. en-copyright= kn-copyright= en-aut-name=KuriharaMarie en-aut-sei=Kurihara en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ThielVera en-aut-sei=Thiel en-aut-mei=Vera kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiHirona en-aut-sei=Takahashi en-aut-mei=Hirona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WardDavid M. en-aut-sei=Ward en-aut-mei=David M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BryantDonald A. en-aut-sei=Bryant en-aut-mei=Donald A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaiMakoto en-aut-sei=Sakai en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biological Sciences, Tokyo Metropolitan University kn-affil= affil-num=3 en-affil=Department of Chemistry, Graduate School of Science, Okayama University of Science kn-affil= affil-num=4 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Land Resources and Environmental Sciences, Montana State University kn-affil= affil-num=6 en-affil=Department of Biochemistry and Molecular Biology, The Pennsylvania State University kn-affil= affil-num=7 en-affil=Department of Chemistry, Graduate School of Science, Okayama University of Science kn-affil= affil-num=8 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=9 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=rhodopsin kn-keyword=rhodopsin en-keyword=ion transport kn-keyword=ion transport en-keyword=retinal kn-keyword=retinal en-keyword=isomerization kn-keyword=isomerization en-keyword=optogenetics kn-keyword=optogenetics END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=12 article-no= start-page=eabm2225 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structure and dynamics of Odinarchaeota tubulin and the implications for eukaryotic microtubule evolution en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tubulins are critical for the internal organization of eukaryotic cells, and understanding their emergence is an important question in eukaryogenesis. Asgard archaea are the closest known prokaryotic relatives to eukaryotes. Here, we elucidated the apo and nucleotide-bound x-ray structures of an Asgard tubulin from hydrothermal living Odinarchaeota (OdinTubulin). The guanosine 5′-triphosphate (GTP)?bound structure resembles a microtubule protofilament, with GTP bound between subunits, coordinating the “+” end subunit through a network of water molecules and unexpectedly by two cations. A water molecule is located suitable for GTP hydrolysis. Time course crystallography and electron microscopy revealed conformational changes on GTP hydrolysis. OdinTubulin forms tubules at high temperatures, with short curved protofilaments coiling around the tubule circumference, more similar to FtsZ, rather than running parallel to its length, as in microtubules. Thus, OdinTubulin represents an evolutionary stage intermediate between prokaryotic FtsZ and eukaryotic microtubule-forming tubulins. en-copyright= kn-copyright= en-aut-name=Ak?lCaner en-aut-sei=Ak?l en-aut-mei=Caner kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AliSamson en-aut-sei=Ali en-aut-mei=Samson kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TranLinh T. en-aut-sei=Tran en-aut-mei=Linh T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GaillardJ?r?mie en-aut-sei=Gaillard en-aut-mei=J?r?mie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiWenfei en-aut-sei=Li en-aut-mei=Wenfei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HayashidaKenichi en-aut-sei=Hayashida en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiroseMika en-aut-sei=Hirose en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoTakayuki en-aut-sei=Kato en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OshimaAtsunori en-aut-sei=Oshima en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujishimaKosuke en-aut-sei=Fujishima en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BlanchoinLaurent en-aut-sei=Blanchoin en-aut-mei=Laurent kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NaritaAkihiro en-aut-sei=Narita en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=RobinsonRobert C. en-aut-sei=Robinson en-aut-mei=Robert C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=4 en-affil=University of Grenoble-Alpes, CEA, CNRS, INRA, Interdisciplinary Research Institute of Grenoble, Laboratoire de Physiologie Cellulaire & V?g?tale, CytoMorpho Lab kn-affil= affil-num=5 en-affil=National Laboratory of Solid State Microstructure, Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University kn-affil= affil-num=6 en-affil=Cellular and Structural Physiology Institute (CeSPI), Nagoya University kn-affil= affil-num=7 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=8 en-affil=Institute for Protein Research, Osaka University kn-affil= affil-num=9 en-affil=Cellular and Structural Physiology Institute (CeSPI), Nagoya University kn-affil= affil-num=10 en-affil=Tokyo Institute of Technology, Earth-Life Science Institute (ELSI) kn-affil= affil-num=11 en-affil=University of Grenoble-Alpes, CEA, CNRS, INRA, Interdisciplinary Research Institute of Grenoble, Laboratoire de Physiologie Cellulaire & V?g?tale, CytoMorpho Lab kn-affil= affil-num=12 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=13 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page=98 end-page=108 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=2022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Skin Electrical Impedance Model for Evaluation of the Thickness and Water Content of the Stratum Corneum en-subtitle= kn-subtitle= en-abstract= kn-abstract=Deterioration of the skin barrier function causes symptoms such as allergies because various chemical substances may enter the human body. Quantitative evaluation of the thickness and water content of the stratum corneum is useful as a measure of the skin barrier function in domains such as dermatology, nursing science, and cosmetics development. The stratum corneum is responsible for most of the skin barrier function, and two factors?the thickness and water content of the stratum corneum?are thus important. In this paper, the stratum corneum is regarded as a parallel model of resistance and capacitance. From measurements of the electrical impedance of the skin, we propose a new model for simultaneous estimation of the thickness and water content of the stratum corneum conventionally measured by a confocal laser scanning microscope and a confocal Raman spectrometer, respectively, and we discuss the results of the measurements. The electrical impedance of the skin was measured using a device that we developed. The measurement began 3 seconds after the electrodes on the measurement head of the device came into contact with the skin, and parameters including the impedance, which was obtained by applying an alternating current signal at two frequencies, were measured. We measured the thickness and water content of the stratum corneum using confocal laser microscopy and confocal Raman spectroscopy, respectively; investigated the relationship of the thickness and water content of the stratum corneum with the electrical impedance of the skin; and established a new potential model for estimating the thickness and water content of the stratum corneum from the parallel resistance and capacitance. The correlation coefficients of the verification data were 0.931 and 0.776, respectively; and the root-mean-squared error of the thickness of the stratum corneum was 2.3??m, while the root-mean-squared error of the water content at the surface of the stratum corneum was 5.4 points. These findings indicate the feasibility of quantitative evaluation of the thickness and water content of the stratum corneum by measuring skin electrical impedance. en-copyright= kn-copyright= en-aut-name=UeharaOsamu en-aut-sei=Uehara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KusuharaToshimasa en-aut-sei=Kusuhara en-aut-mei=Toshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuzakiKenichi en-aut-sei=Matsuzaki en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoYoshitake en-aut-sei=Yamamoto en-aut-mei=Yoshitake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraTakao en-aut-sei=Nakamura en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Medical Engineering Laboratory, ALCARE CO., Ltd. kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Medical Engineering Laboratory, ALCARE CO., Ltd. kn-affil= affil-num=4 en-affil=Okayama University kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=skin electrical impedance kn-keyword=skin electrical impedance en-keyword=thickness kn-keyword=thickness en-keyword=water content kn-keyword=water content en-keyword=stratum corneum kn-keyword=stratum corneum en-keyword=skin barrier kn-keyword=skin barrier END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page=151 end-page=161 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=2022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Trial of Sportswear Type ECG Sensor Device for Cardiac Safety Management during Marathon Running en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cardiac arrest has been reported during participation in several sports. Of these sports, marathon running is a particularly popular sport but imposes high cardiac load. Indeed, its popularity has been growing worldwide. Risk of cardiac arrest during marathon races is also expected to increase. Several studies have recorded electrocardiographic (ECG) information during marathon races to protect athletes from cardiac arrest. Although evaluable ECG data have been obtained and analyzed, cost-effectiveness of the system, data quality, and clinical significance remain inadequate. This report is the first to describe an economical electrocardiograph built into a T-shirt for use during marathon race. Twenty healthy runners aged 20 to 59 years (mean 36 years) wore the ECG device while running. The ECG data were monitored and analyzed to assess the observed frequencies of specified arrhythmias and the sections of the marathon in which the arrhythmias occurred. Of the ECG data obtained from 14 runners who completed the full marathon, six ECG datasets were evaluable. In some runners, there was inadequate contact between the electrode and body surface or poor Bluetooth connection between the ECG wireless transmitter and smartphone. Regarding arrhythmia analysis, all evaluable data that were analyzed showed some rhythm fluctuations. In conclusion, this economical T-shirt type ECG sensor provided evaluable ECG data during marathon races, although the evaluable rate was not high. The data were used to analyze specified arrhythmias, but some difficulties were encountered. The ECG sensor did not function properly because of a system error. The ECG sensor was not adequately moistened to record ECGs accurately. Moreover, some runners chose an unsuitable shirt size, which impaired the stability and strength of the electrode?skin contact. These shortcomings produced noise in the ECG data, which made it difficult to analyze arrhythmias. The next step will be to solve these problems and acquire data from a large number of runners. en-copyright= kn-copyright= en-aut-name=YamaneTakahiro en-aut-sei=Yamane en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiranoKazuya en-aut-sei=Hirano en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiraiKenta en-aut-sei=Hirai en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakanoNoriko en-aut-sei=Sakano en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritaMizuki en-aut-sei=Morita en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OozawaSusumu en-aut-sei=Oozawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Biomedical Informatics, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Biomedical Informatics, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Biomedical Informatics, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Clinical Safety, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= en-keyword=electrocardiogram kn-keyword=electrocardiogram en-keyword=distance running kn-keyword=distance running en-keyword=prevention kn-keyword=prevention en-keyword=sudden cardiac arrest kn-keyword=sudden cardiac arrest en-keyword=T-shirt type sensor kn-keyword=T-shirt type sensor END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=16 article-no= start-page=5174 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230809 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Switching to Dupilumab from Other Biologics without a Treatment Interval in Patients with Severe Asthma: A Multi-Center Retrospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Dupilumab is a fully humanized monoclonal antibody that blocks interleukin4 and interleukin-13 signals. Several large clinical trials have demonstrated the efficacy of dupilumab in patients with severe asthma. However, few studies have examined a switch to dupilumab from other biologics. Methods: This retrospective, multi-center observational study was conducted by the Okayama Respiratory Disease Study Group. Consecutive patients with severe asthma who were switched to dupilumab from other biologics without a treatment interval between May 2019 and September 2021 were enrolled. Patients with a treatment interval of more than twice the standard dosing interval for the previous biologic prior to dupilumab administration were excluded. Results: The median patient age of the 27 patients enrolled in this study was 57 years (IQR, 45-68 years). Eosinophilic chronic rhinosinusitis (ECRS)/chronic rhinosinusitis with nasal polyp (CRSwNP) was confirmed in 23 patients. Previous biologics consisted of omalizumab (n = 3), mepolizumab (n = 3), and benralizumab (n = 21). Dupilumab significantly improved FEV1 (median improvement: +145 mL) and the asthma control test score (median improvement: +2). The overall response rate in patients receiving dupilumab for asthma as determined using the Global Evaluations of Treatment Effectiveness (GETE) was 77.8%. There were no significant differences in the baseline characteristics of the GETE-improved group vs. the non-GETE-improved group. ECRS/CRSwNP improved in 20 of the 23 patients (87.0%). Overall, 8 of the 27 patients (29.6%) developed transient hypereosinophilia (>1500/ mu L), but all were asymptomatic and able to continue dupilumab therapy. Conclusions: Dupilumab was highly effective for the treatment of severe asthma and ECRS/CRSwNP, even in patients switched from other biologics without a treatment interval. en-copyright= kn-copyright= en-aut-name=HigoHisao en-aut-sei=Higo en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchikawaHirohisa en-aut-sei=Ichikawa en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ArakawaYukako en-aut-sei=Arakawa en-aut-mei=Yukako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriYoshihiro en-aut-sei=Mori en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItanoJunko en-aut-sei=Itano en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SenooSatoru en-aut-sei=Senoo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KimuraGoro en-aut-sei=Kimura en-aut-mei=Goro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TanimotoYasushi en-aut-sei=Tanimoto en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyakeKohei en-aut-sei=Miyake en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatsutaTomoya en-aut-sei=Katsuta en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KataokaMikio en-aut-sei=Kataoka en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Okayama Respiratory Disease Study Group (ORDSG) en-aut-sei=Okayama Respiratory Disease Study Group (ORDSG) en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital kn-affil= affil-num=5 en-affil=Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=9 en-affil=Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center kn-affil= affil-num=10 en-affil=Department of Respiratory Medicine, National Hospital Organization Himeji Medical Center kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, Onomichi Municipal Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil= kn-affil= en-keyword=dupilumab kn-keyword=dupilumab en-keyword=severe asthma kn-keyword=severe asthma en-keyword=treatment interval kn-keyword=treatment interval en-keyword=eosinophilic chronic rhinosinusitis kn-keyword=eosinophilic chronic rhinosinusitis END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=7 article-no= start-page=739 end-page=753 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mixed Response to Cancer Immunotherapy is Driven by Intratumor Heterogeneity and Differential Interlesion Immune Infiltration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Some patients experience mixed response to immunotherapy, whose biological mechanisms and clinical impact have been obscure. We obtained two tumor samples from lymph node (LN) metastatic lesions in a same patient. Whole exome sequencing for the both tumors and single-cell sequencing for the both tumor-infiltrating lymphocytes (TIL) demonstrated a significant difference in tumor clonality and TILs' characteristics, especially exhausted T-cell clonotypes, although a close relationship between the tumor cell and T-cell clones were observed as a response of an overlapped exhausted T-cell clone to an overlapped neoantigen. To mimic the clinical setting, we generated a mouse model of several clones from a same tumor cell line. Similarly, differential tumor clones harbored distinct TILs, and one responded to programmed cell death protein 1 (PD-1) blockade but the other did not in this model. We further conducted cohort study (n = 503) treated with PD-1 blockade monotherapies to investigate the outcome of mixed response. Patients with mixed responses to PD-1 blockade had a poor prognosis in our cohort. Particularly, there were significant differences in both tumor and T-cell clones between the primary and LN lesions in a patient who experienced tumor response to anti-PD-1 mAb followed by disease progression in only LN metastasis. Our results underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome.
Significance: Several patients experience mixed responses to immunotherapies, but the biological mechanisms and clinical significance remain unclear. Our results from clinical and mouse studies underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome. en-copyright= kn-copyright= en-aut-name=MorinagaTakao en-aut-sei=Morinaga en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaxNicolas en-aut-sei=Sax en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamashitaKazuo en-aut-sei=Yamashita en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawashimaShusuke en-aut-sei=Kawashima en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UenoToshihide en-aut-sei=Ueno en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LinJason en-aut-sei=Lin en-aut-mei=Jason kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OharaYuuki en-aut-sei=Ohara en-aut-mei=Yuuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KuwataTakeshi en-aut-sei=Kuwata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YukamiHiroki en-aut-sei=Yukami en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawazoeAkihito en-aut-sei=Kawazoe en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShitaraKohei en-aut-sei=Shitara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OhnumaTakehiro en-aut-sei=Ohnuma en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UmedaYoshiyasu en-aut-sei=Umeda en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KawaharaYu en-aut-sei=Kawahara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=NakamuraYasuhiro en-aut-sei=Nakamura en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KiniwaYukiko en-aut-sei=Kiniwa en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=EnokidaTomohiro en-aut-sei=Enokida en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=TaharaMakoto en-aut-sei=Tahara en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=HasegawaYoshinori en-aut-sei=Hasegawa en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=SuzukiYutaka en-aut-sei=Suzuki en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=NishikawaHiroyoshi en-aut-sei=Nishikawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=2 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=3 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=4 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=KOTAI Biotechnologies Inc kn-affil= affil-num=6 en-affil=KOTAI Biotechnologies Inc kn-affil= affil-num=7 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=8 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=10 en-affil=Chiba Cancer Center, Research Institute kn-affil= affil-num=11 en-affil=Department of Pathology, National Cancer Center Hospital East kn-affil= affil-num=12 en-affil=Department of Genetic Medicineand Services, National Cancer Center Hospital East kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East kn-affil= affil-num=14 en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East kn-affil= affil-num=15 en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East kn-affil= affil-num=16 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=17 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=18 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=19 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=20 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=21 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=22 en-affil=Department of Dermatology, Shinshu University School of Medicine kn-affil= affil-num=23 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=24 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=26 en-affil=Department of Head and Neck Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=27 en-affil=Department of Head and Neck Medical Oncology, National Cancer Center Hospital East kn-affil= affil-num=28 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=29 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=30 en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=31 en-affil=Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center kn-affil= affil-num=32 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue=1 article-no= start-page=101046 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Expression of microbial rhodopsins in Escherichia coli and their extraction and purification using styrene-maleic acid copolymers en-subtitle= kn-subtitle= en-abstract= kn-abstract=Microbial rhodopsins are photoreceptive membrane proteins showing various light-dependent biological activities. Styrene-maleic acid (SMA) copolymers spontaneously form nanoscale lipid particles containing membrane proteins and associated lipids without detergent, and can be used to characterize membrane molecules. Here, we provide a protocol to functionally express a thermally stable rhodopsin, Rubrobacter xylanophilus rhodopsin, and an unstable rhodopsin, Halobacterium salinarum sensory rhodopsin I, in Escherichia coli. We then describe the preparation of SMA and the extraction and purification of rhodopsin molecules using SMA.
For complete details on the use and execution of this protocol, please refer to Ueta et al. (2020). 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=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2005 dt-pub=20050930 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=三環性融合ピリミジン類の合成と生物活性分子設計 kn-title=Synthesis and biological active molecular design of tricyclic fused pyrimidines en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Shoeb Ahmed en-aut-sei=Shoeb Ahmed en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=236 cd-vols= no-issue=3 article-no= start-page=864 end-page=877 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220817 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A tonoplast‐localized magnesium transporter is crucial for stomatal opening in Arabidopsis under high Mg2+ conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plant stomata play an important role in CO2 uptake for photosynthesis and transpiration, but the mechanisms underlying stomatal opening and closing under changing environmental conditions are still not completely understood.
Through large-scale genetic screening, we isolated an Arabidopsis mutant (closed stomata2 (cst2)) that is defective in stomatal opening. We cloned the causal gene (MGR1/CST2) and functionally characterized this gene.
The mutant phenotype was caused by a mutation in a gene encoding an unknown protein with similarities to the human magnesium (Mg2+) efflux transporter ACDP/CNNM. MGR1/CST2 was localized to the tonoplast and showed transport activity for Mg2+. This protein was constitutively and highly expressed in guard cells. Knockout of this gene resulted in stomatal closing, decreased photosynthesis and growth retardation, especially under high Mg2+ conditions, while overexpression of this gene increased stomatal opening and tolerance to high Mg2+ concentrations. Furthermore, guard cell-specific expression of MGR1/CST2 in the mutant partially restored its stomatal opening.
Our results indicate that MGR1/CST2 expression in the leaf guard cells plays an important role in maintaining cytosolic Mg2+ concentrations through sequestering Mg2+ into vacuoles, which is required for stomatal opening, especially under high Mg2+ conditions. en-copyright= kn-copyright= en-aut-name=InoueShin‐ichiro en-aut-sei=Inoue en-aut-mei=Shin‐ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiMaki en-aut-sei=Hayashi en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangSheng en-aut-sei=Huang en-aut-mei=Sheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YokoshoKengo en-aut-sei=Yokosho en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotohEiji en-aut-sei=Gotoh en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkematsuShuka en-aut-sei=Ikematsu en-aut-mei=Shuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkumuraMasaki en-aut-sei=Okumura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SuzukiTakamasa en-aut-sei=Suzuki en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KamuraTakumi en-aut-sei=Kamura en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KinoshitaToshinori en-aut-sei=Kinoshita en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=2 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Department of Forest Environmental Sciences, Faculty of Agriculture, Kyushu University kn-affil= affil-num=6 en-affil=Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University kn-affil= affil-num=7 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=8 en-affil=Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=9 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=10 en-affil=Division of Biological Science, Graduate School of Science, Nagoya University kn-affil= affil-num=11 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=ACDP kn-keyword=ACDP en-keyword=CNNM kn-keyword=CNNM en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=magnesium transport kn-keyword=magnesium transport en-keyword=plant growth kn-keyword=plant growth en-keyword=stomatal opening kn-keyword=stomatal opening END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=4 article-no= start-page=387 end-page=394 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between Radon Hot Spring Bathing and Health Conditions: A Cross-Sectional Study in Misasa, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=No epidemiological studies have examined the health effects of daily bathing in radon hot springs. In this cross-sectional study, we investigated the associations between radon hot spring bathing and health conditions. The target population was 5,250 adults ? 20 years old in the town of Misasa, Japan. We collected information about the participants’ bathing habits and alleviation of a variety of disease symptoms, and their self-rated health (SRH). Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated. In both the adjusted and unadjusted models of hypertension, significant associations between the > 1×/week hot spring bathing and the alleviation of hypertension symptoms were observed compared to the group whose hot spring bathing was <1×/week: adjusted model, OR 5.40 (95%CI: 1.98-14.74); unadjusted model, 3.67 (1.50-8.99) and for gastroenteritis: adjusted model, 9.18 (1.15-72.96); unadjusted model, 7.62 (1.59-36.49). Compared to the no-bathing group, higher SRH was significantly associated with both bathing < 1×/week: unadjusted model, 2.27 (1.53-3.37) and > 1×/week: adjusted model, 1.91 (1.15-3.19). These findings suggest that bathing in radon hot springs is associated with higher SRH and the alleviation of hypertension and gastroenteritis. en-copyright= kn-copyright= en-aut-name=KataokaTakahiro en-aut-sei=Kataoka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HabuHiroshi en-aut-sei=Habu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaAyumi en-aut-sei=Tanaka en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaoeShota en-aut-sei=Naoe en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiKaito en-aut-sei=Murakami en-aut-mei=Kaito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimotoYuki en-aut-sei=Fujimoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YukimineRyohei en-aut-sei=Yukimine en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MitsunobuFumihiro en-aut-sei=Mitsunobu en-aut-mei=Fumihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamaokaKiyonori en-aut-sei=Yamaoka en-aut-mei=Kiyonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Longevity and Social Medicine (Geriatrics), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Radiological Technology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=radon hot spring kn-keyword=radon hot spring en-keyword=bathing habit kn-keyword=bathing habit en-keyword=self-rated health kn-keyword=self-rated health en-keyword=cross-section study kn-keyword=cross-section study END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=4 article-no= start-page=341 end-page=345 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biological Roles of Hepatitis B Viral X Protein in the Viral Replication and Hepatocarcinogenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hepatitis B virus is a pathogenic virus that infects 300 million people worldwide and causes chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Hepatitis B virus encodes four proteins. Among them, the HBx protein plays a central role in the HBV pathogenesis. Because the HBx protein is considered to play a central role in the induction of viral replication and hepatocarcinogenesis, the regulation of its function could be a key factor in the development of new interventions against hepatitis B. In this review, HBx protein-related viral replication and hepatocarcinogenesis mechanisms are described, with a focus on the recently reported viral replication mechanisms related to degradation of the Smc5/6 protein complex. We also discuss our recent discovery of a compound that inhibits HBx protein-induced degradation of the Smc5/6 protein complex, and that exerts inhibitory effects on both viral replication and hepatocarcinogenesis. Finally, prospects for future research on the HBx protein are described. en-copyright= kn-copyright= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Academic Field of Medicine, Density and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=HBx kn-keyword=HBx en-keyword=Smc5/6 kn-keyword=Smc5/6 en-keyword=DDB1 kn-keyword=DDB1 en-keyword=nitazoxianide kn-keyword=nitazoxianide en-keyword=DNA repair kn-keyword=DNA repair END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=621 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=DNA methyltransferases (DNMTs) catalyze methylation at the C5 position of cytosine with S-adenosyl-l-methionine. Methylation regulates gene expression, serving a variety of physiological and pathophysiological roles. The chemical mechanisms regulating DNMT enzymatic activity, however, are not fully elucidated. Here, we show that protein S-nitrosylation of a cysteine residue in DNMT3B attenuates DNMT3B enzymatic activity and consequent aberrant upregulation of gene expression. These genes include Cyclin D2 (Ccnd2), which is required for neoplastic cell proliferation in some tumor types. In cell-based and in vivo cancer models, only DNMT3B enzymatic activity, and not DNMT1 or DNMT3A, affects Ccnd2 expression. Using structure-based virtual screening, we discovered chemical compounds that specifically inhibit S-nitrosylation without directly affecting DNMT3B enzymatic activity. The lead compound, designated DBIC, inhibits S-nitrosylation of DNMT3B at low concentrations (IC50 <= 100nM). Treatment with DBIC prevents nitric oxide (NO)-induced conversion of human colonic adenoma to adenocarcinoma in vitro. Additionally, in vivo treatment with DBIC strongly attenuates tumor development in a mouse model of carcinogenesis triggered by inflammation-induced generation of NO. Our results demonstrate that de novo DNA methylation mediated by DNMT3B is regulated by NO, and DBIC protects against tumor formation by preventing aberrant S-nitrosylation of DNMT3B. en-copyright= kn-copyright= en-aut-name=OkudaKosaku en-aut-sei=Okuda en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaharaKengo en-aut-sei=Nakahara en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItoAkihiro en-aut-sei=Ito en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IijimaYuta en-aut-sei=Iijima en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NomuraRyosuke en-aut-sei=Nomura en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KumarAshutosh en-aut-sei=Kumar en-aut-mei=Ashutosh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujikawaKana en-aut-sei=Fujikawa en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AdachiKazuya en-aut-sei=Adachi en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimadaYuki en-aut-sei=Shimada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujioSatoshi en-aut-sei=Fujio en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoReina en-aut-sei=Yamamoto en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OnumaKunishige en-aut-sei=Onuma en-aut-mei=Kunishige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OsakiMitsuhiko en-aut-sei=Osaki en-aut-mei=Mitsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OkadaFutoshi en-aut-sei=Okada en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UkegawaTaichi en-aut-sei=Ukegawa en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakeuchiYasuo en-aut-sei=Takeuchi en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YasuiNorihisa en-aut-sei=Yasui en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamashitaAtsuko en-aut-sei=Yamashita en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MarusawaHiroyuki en-aut-sei=Marusawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MatsushitaYosuke en-aut-sei=Matsushita en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KatagiriToyomasa en-aut-sei=Katagiri en-aut-mei=Toyomasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ShibataTakahiro en-aut-sei=Shibata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=UchidaKoji en-aut-sei=Uchida en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NiuSheng-Yong en-aut-sei=Niu en-aut-mei=Sheng-Yong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=LangNhi B. en-aut-sei=Lang en-aut-mei=Nhi B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakamuraTomohiro en-aut-sei=Nakamura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=ZhangKam Y. J. en-aut-sei=Zhang en-aut-mei=Kam Y. J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=LiptonStuart A. en-aut-sei=Lipton en-aut-mei=Stuart A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=4 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN kn-affil= affil-num=7 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Division of Experimental Pathology, Faculty of Medicine, Tottori University kn-affil= affil-num=14 en-affil=Division of Experimental Pathology, Faculty of Medicine, Tottori University kn-affil= affil-num=15 en-affil=Division of Experimental Pathology, Faculty of Medicine, Tottori University kn-affil= affil-num=16 en-affil=Department of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Laboratory of Structural Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=19 en-affil=Laboratory of Structural Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=21 en-affil=Division of Genome Medicine, Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=22 en-affil=Division of Genome Medicine, Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=23 en-affil=Graduate School of Bioagricultural Sciences, Nagoya University kn-affil= affil-num=24 en-affil=Laboratory of Food Chemistry, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo kn-affil= affil-num=25 en-affil=Broad Institute of MIT and Harvard kn-affil= affil-num=26 en-affil=Neurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute kn-affil= affil-num=27 en-affil=Neurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute kn-affil= affil-num=28 en-affil=Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN kn-affil= affil-num=29 en-affil=Neurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute kn-affil= affil-num=30 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=8954 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Refining the evolutionary tree of the horse Y chromosome en-subtitle= kn-subtitle= en-abstract= kn-abstract=The Y chromosome carries information about the demography of paternal lineages, and thus, can prove invaluable for retracing both the evolutionary trajectory of wild animals and the breeding history of domesticates. In horses, the Y chromosome shows a limited, but highly informative, sequence diversity, supporting the increasing breeding influence of Oriental lineages during the last 1500 years. Here, we augment the primary horse Y-phylogeny, which is currently mainly based on modern horse breeds of economic interest, with haplotypes (HT) segregating in remote horse populations around the world. We analyze target enriched sequencing data of 5 Mb of the Y chromosome from 76 domestic males, together with 89 whole genome sequenced domestic males and five Przewalski's horses from previous studies. The resulting phylogeny comprises 153 HTs defined by 2966 variants and offers unprecedented resolution into the history of horse paternal lineages. It reveals the presence of a remarkable number of previously unknown haplogroups in Mongolian horses and insular populations. Phylogenetic placement of HTs retrieved from 163 archaeological specimens further indicates that most of the present-day Y-chromosomal variation evolved after the domestication process that started around 4200 years ago in the Western Eurasian steppes. Our comprehensive phylogeny significantly reduces ascertainment bias and constitutes a robust evolutionary framework for analyzing horse population dynamics and diversity. en-copyright= kn-copyright= en-aut-name=BozlakElif en-aut-sei=Bozlak en-aut-mei=Elif kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RadovicLara en-aut-sei=Radovic en-aut-mei=Lara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=RemerViktoria en-aut-sei=Remer en-aut-mei=Viktoria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=RiglerDoris en-aut-sei=Rigler en-aut-mei=Doris kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AllenLucy en-aut-sei=Allen en-aut-mei=Lucy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BremGottfried en-aut-sei=Brem en-aut-mei=Gottfried kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=StalderGabrielle en-aut-sei=Stalder en-aut-mei=Gabrielle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CastanedaCaitlin en-aut-sei=Castaneda en-aut-mei=Caitlin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CothranGus en-aut-sei=Cothran en-aut-mei=Gus kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=RaudseppTerje en-aut-sei=Raudsepp en-aut-mei=Terje kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkudaYu en-aut-sei=Okuda en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoeKyaw Kyaw en-aut-sei=Moe en-aut-mei=Kyaw Kyaw kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoeHla Hla en-aut-sei=Moe en-aut-mei=Hla Hla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KounnavongsaBounthavone en-aut-sei=Kounnavongsa en-aut-mei=Bounthavone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KeonouchanhSoukanh en-aut-sei=Keonouchanh en-aut-mei=Soukanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=VanNguyen Huu en-aut-sei=Van en-aut-mei=Nguyen Huu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=VuVan Hai en-aut-sei=Vu en-aut-mei=Van Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ShahManoj Kumar en-aut-sei=Shah en-aut-mei=Manoj Kumar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NishiboriMasahide en-aut-sei=Nishibori en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KazymbetPolat en-aut-sei=Kazymbet en-aut-mei=Polat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=BakhtinMeirat en-aut-sei=Bakhtin en-aut-mei=Meirat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ZhunushovAsankadyr en-aut-sei=Zhunushov en-aut-mei=Asankadyr kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=PaulRipon Chandra en-aut-sei=Paul en-aut-mei=Ripon Chandra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=DashnyamBumbein en-aut-sei=Dashnyam en-aut-mei=Bumbein kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NozawaKen en-aut-sei=Nozawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=AlmarzookSaria en-aut-sei=Almarzook en-aut-mei=Saria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=BrockmannGudrun A. en-aut-sei=Brockmann en-aut-mei=Gudrun A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=ReissmannMonika en-aut-sei=Reissmann en-aut-mei=Monika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=AntczakDouglas F. en-aut-sei=Antczak en-aut-mei=Douglas F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=MillerDonald C. en-aut-sei=Miller en-aut-mei=Donald C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=SadeghiRaheleh en-aut-sei=Sadeghi en-aut-mei=Raheleh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=Butler-WemkenInes von en-aut-sei=Butler-Wemken en-aut-mei=Ines von kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KostarasNikos en-aut-sei=Kostaras en-aut-mei=Nikos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HanHaige en-aut-sei=Han en-aut-mei=Haige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=ManglaiDugarjaviin en-aut-sei=Manglai en-aut-mei=Dugarjaviin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=AbdurasulovAbdugani en-aut-sei=Abdurasulov en-aut-mei=Abdugani kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=SukhbaatarBoldbaatar en-aut-sei=Sukhbaatar en-aut-mei=Boldbaatar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=Ropka-MolikKatarzyna en-aut-sei=Ropka-Molik en-aut-mei=Katarzyna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=Stefaniuk-SzmukierMonika en-aut-sei=Stefaniuk-Szmukier en-aut-mei=Monika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=LopesMaria Susana en-aut-sei=Lopes en-aut-mei=Maria Susana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=MachadoArtur da C?mara en-aut-sei=Machado en-aut-mei=Artur da C?mara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=KalashnikovValery V. en-aut-sei=Kalashnikov en-aut-mei=Valery V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=KalinkovaLiliya en-aut-sei=Kalinkova en-aut-mei=Liliya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=ZaitevAlexander M. en-aut-sei=Zaitev en-aut-mei=Alexander M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=Novoa-BravoMiguel en-aut-sei=Novoa-Bravo en-aut-mei=Miguel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=LindgrenGabriella en-aut-sei=Lindgren en-aut-mei=Gabriella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=BrooksSamantha en-aut-sei=Brooks en-aut-mei=Samantha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=RosaLaura Patterson en-aut-sei=Rosa en-aut-mei=Laura Patterson kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=OrlandoLudovic en-aut-sei=Orlando en-aut-mei=Ludovic kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=JurasRytis en-aut-sei=Juras en-aut-mei=Rytis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=KuniedaTetsuo en-aut-sei=Kunieda en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=WallnerBarbara en-aut-sei=Wallner en-aut-mei=Barbara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= affil-num=1 en-affil=Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna kn-affil= affil-num=2 en-affil=Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna kn-affil= affil-num=3 en-affil=Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna kn-affil= affil-num=4 en-affil=Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna kn-affil= affil-num=5 en-affil=Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna kn-affil= affil-num=6 en-affil=Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna kn-affil= affil-num=7 en-affil=Research Institute of Wildlife Ecology, University of Veterinary Medicine Vienna kn-affil= affil-num=8 en-affil=School of Veterinary Medicine and Biomedical Sciences, Texas A&M University kn-affil= affil-num=9 en-affil=School of Veterinary Medicine and Biomedical Sciences, Texas A&M University kn-affil= affil-num=10 en-affil=School of Veterinary Medicine and Biomedical Sciences, Texas A&M University kn-affil= affil-num=11 en-affil=Museum of Dinosaur Research, Okayama University of Science kn-affil= affil-num=12 en-affil=Department of Pathology and Microbiology, University of Veterinary Science kn-affil= affil-num=13 en-affil=Department of Genetics and Animal Breeding, University of Veterinary Science kn-affil= affil-num=14 en-affil=National Agriculture and Forestry Research Institute (Lao) Resources, Livestock Research Center kn-affil= affil-num=15 en-affil=Faculty of Animal Science and Veterinary Medicine, University of Agriculture and Forestry, Hue University kn-affil= affil-num=16 en-affil=Faculty of Animal Science and Veterinary Medicine, University of Agriculture and Forestry, Hue University kn-affil= affil-num=17 en-affil=Faculty of Animal Science and Veterinary Medicine, University of Agriculture and Forestry, Hue University kn-affil= affil-num=18 en-affil=Faculty of Animal Science, Veterinary Science and Fisheries, Agriculture and Forestry University kn-affil= affil-num=19 en-affil=Graduate School of Integrated Sciences for Life, Hiroshima University kn-affil= affil-num=20 en-affil=Radiobiological Research Institute, JSC Astana Medical University kn-affil= affil-num=21 en-affil=Institute of Biotechnology, National Academy of Sciences of the Kyrgyz Republic kn-affil= affil-num=22 en-affil=Institute of Biotechnology, National Academy of Sciences of the Kyrgyz Republic kn-affil= affil-num=23 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=24 en-affil=Institute of Biological Sciences, Mongolian Academy of Sciences kn-affil= affil-num=25 en-affil=Primate Research Institute, Kyoto University kn-affil= affil-num=26 en-affil=Albrecht Daniel Thaer?Institut, Humboldt-Universit?t zu Berlin kn-affil= affil-num=27 en-affil=Albrecht Daniel Thaer?Institut, Humboldt-Universit?t zu Berlin kn-affil= affil-num=28 en-affil=Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University kn-affil= affil-num=29 en-affil=Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University kn-affil= affil-num=30 en-affil=Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University kn-affil= affil-num=31 en-affil=Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University kn-affil= affil-num=32 en-affil=Barb Horse Breeding Organisation VFZB E. V., Verein der Freunde und Z?chter Des Berberpferdes E.V. kn-affil= affil-num=33 en-affil=Amaltheia kn-affil= affil-num=34 en-affil=Inner Mongolia Key Laboratory of Equine Genetics, Breeding and Reproduction, College of Animal Science, Equine Research Center, Inner Mongolia Agricultural University kn-affil= affil-num=35 en-affil=Inner Mongolia Key Laboratory of Equine Genetics, Breeding and Reproduction, College of Animal Science, Equine Research Center, Inner Mongolia Agricultural University kn-affil= affil-num=36 en-affil=Department of Agriculture, Faculty of Natural Sciences and Geography, Osh State University kn-affil= affil-num=37 en-affil=Sector of Surveillance and Diagnosis of Infectious Diseases, State Central Veterinary Laboratory kn-affil= affil-num=38 en-affil=National Research Institute of Animal Production, Animal Molecular Biology kn-affil= affil-num=39 en-affil=National Research Institute of Animal Production, Animal Molecular Biology kn-affil= affil-num=40 en-affil=Biotechnology Centre of Azores, University of Azores kn-affil= affil-num=41 en-affil=Biotechnology Centre of Azores, University of Azores kn-affil= affil-num=42 en-affil=All-Russian Research Institute for Horse Breeding kn-affil= affil-num=43 en-affil=All-Russian Research Institute for Horse Breeding kn-affil= affil-num=44 en-affil=All-Russian Research Institute for Horse Breeding kn-affil= affil-num=45 en-affil=Gen?tica Animal de Colombia SAS. kn-affil= affil-num=46 en-affil=Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences kn-affil= affil-num=47 en-affil=Department of Animal Science, UF Genetics Institute, University of Florida kn-affil= affil-num=48 en-affil=Department of Agriculture and Industry, Sul Ross State University kn-affil= affil-num=49 en-affil=Centre d’Anthropobiologie et de G?nomique de Toulouse, Universit? Paul Sabatier kn-affil= affil-num=50 en-affil=School of Veterinary Medicine and Biomedical Sciences, Texas A&M University kn-affil= affil-num=51 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=52 en-affil=Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna kn-affil= END start-ver=1.4 cd-journal=joma no-vol=299 cd-vols= no-issue=5 article-no= start-page=104571 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Actin-rich lamellipodia-like protrusions contribute to the integrity of epithelial cell-cell junctions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metastasis-suppressor 1 (MTSS1) is a membrane-interacting scaffolding protein that regulates the integrity of epithelial cell-cell junctions and functions as a tumor suppressor in a wide range of carcinomas. MTSS1 binds phosphoinositide-rich membranes through its I-BAR domain and is capable of sensing and generating negative membrane curvature in vitro. However, the mechanisms by which MTSS1 localizes to inter-cellular junctions in epithelial cells and contributes to their integrity and maintenance have remained elusive. By carrying out EM and live-cell imaging on cultured Madin-Darby canine kidney cell monolayers, we provide evidence that adherens junctions of epithelial cells harbor lamellipodia-like, dynamic actin-driven membrane folds, which exhibit high negative membrane curvature at their distal edges. BioID proteomics and imaging experiments demonstrated that MTSS1 associates with an Arp2/3 complex activator, the WAVE-2 complex, in dynamic actin-rich protrusions at cell-cell junctions. Inhibi-tion of Arp2/3 or WAVE-2 suppressed actin filament assembly at adherens junctions, decreased the dynamics of junctional membrane protrusions, and led to defects in epithelial integ-rity. Together, these results support a model in which membrane-associated MTSS1, together with the WAVE-2 and Arp2/3 complexes, promotes the formation of dynamic lamellipodia-like actin protrusions that contribute to the integrity of cell-cell junctions in epithelial monolayers. en-copyright= kn-copyright= en-aut-name=SenjuYosuke en-aut-sei=Senju en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MushtaqToiba en-aut-sei=Mushtaq en-aut-mei=Toiba kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=VihinenHelena en-aut-sei=Vihinen en-aut-mei=Helena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ManninenAki en-aut-sei=Manninen en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaarikangasJuha en-aut-sei=Saarikangas en-aut-mei=Juha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=VenKatharina en-aut-sei=Ven en-aut-mei=Katharina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EngelUlrike en-aut-sei=Engel en-aut-mei=Ulrike kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=VarjosaloMarkku en-aut-sei=Varjosalo en-aut-mei=Markku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=JokitaloEija en-aut-sei=Jokitalo en-aut-mei=Eija kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LappalainenPekka en-aut-sei=Lappalainen en-aut-mei=Pekka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science (RIIS), Okayama University kn-affil= affil-num=2 en-affil=Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki kn-affil= affil-num=3 en-affil=Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki kn-affil= affil-num=4 en-affil=Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu kn-affil= affil-num=5 en-affil=Helsinki Institute of Life Science (HiLIFE), University of Helsinki kn-affil= affil-num=6 en-affil=Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki kn-affil= affil-num=7 en-affil=Nikon Imaging Center and Centre for Organismal Studies, Heidelberg University kn-affil= affil-num=8 en-affil=Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki kn-affil= affil-num=9 en-affil=Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki kn-affil= affil-num=10 en-affil=Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=920 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230217 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structure of a monomeric photosystem I core associated with iron-stress-induced-A proteins from Anabaena sp. PCC 7120 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Iron-stress-induced-A proteins (IsiAs) are expressed in cyanobacteria under iron-deficient conditions. The cyanobacterium Anabaena sp. PCC 7120 has four isiA genes; however, their binding property and functional roles in PSI are still missing. We analyzed a cryo-electron microscopy structure of a PSI-IsiA supercomplex isolated from Anabaena grown under an iron-deficient condition. The PSI-IsiA structure contains six IsiA subunits associated with the PsaA side of a PSI core monomer. Three of the six IsiA subunits were identified as IsiA1 and IsiA2. The PSI-IsiA structure lacks a PsaL subunit; instead, a C-terminal domain of IsiA2 occupies the position of PsaL, which inhibits the oligomerization of PSI, leading to the formation of a PSI monomer. Furthermore, excitation-energy transfer from IsiAs to PSI appeared with a time constant of 55 ps. These findings provide insights into both the molecular assembly of the Anabaena IsiA family and the functional roles of IsiAs. en-copyright= kn-copyright= en-aut-name=NagaoRyo en-aut-sei=Nagao en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamaguchiTasuku en-aut-sei=Hamaguchi en-aut-mei=Tasuku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UenoYoshifumi en-aut-sei=Ueno en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsuboshitaNaoki en-aut-sei=Tsuboshita en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimizuShota en-aut-sei=Shimizu en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FurutaniMiyu en-aut-sei=Furutani en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=EhiraShigeki en-aut-sei=Ehira en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawakamiKeisuke en-aut-sei=Kawakami en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SuzukiTakehiro en-aut-sei=Suzuki en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DohmaeNaoshi en-aut-sei=Dohmae en-aut-mei=Naoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AkimotoSeiji en-aut-sei=Akimoto en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YonekuraKoji en-aut-sei=Yonekura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Biostructural Mechanism Laboratory, RIKEN SPring-8 Center kn-affil= affil-num=4 en-affil=Graduate School of Science, Kobe University kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Science, Kobe University kn-affil= affil-num=8 en-affil=Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Biostructural Mechanism Laboratory, RIKEN SPring-8 Center kn-affil= affil-num=11 en-affil=Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=12 en-affil=Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=13 en-affil=Graduate School of Science, Kobe University kn-affil= affil-num=14 en-affil= Biostructural Mechanism Laboratory, RIKEN SPring-8 Center kn-affil= affil-num=15 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=299 cd-vols= no-issue=4 article-no= start-page=104587 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ATP and its metabolite adenosine cooperatively upregulate the antigen-presenting molecules on dendritic cells leading to IFN-gamma production by T cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells (DCs) present foreign antigens to T cells via the major histocompatibility complex (MHC), thereby inducing acquired immune responses. ATP accumulates at sites of inflammation or in tumor tissues, which triggers local inflammatory responses. However, it remains to be clarified how ATP modulates the functions of DCs. In this study, we investigated the effects of extracellular ATP on mouse bone marrow- derived dendritic cells (BMDCs) as well as the potential for subsequent T cell activation. We found that high concentrations of ATP (1 mM) upregulated the cell surface expression levels of MHC-I, MHC-II, and co-stimulatory molecules CD80 and CD86 but not those of co-inhibitory molecules PD-L1 and PD-L2 in BMDCs. Increased surface expression of MHC-I, MHC-II, CD80, and CD86 was inhibited by a pan-P2 receptor antagonist. In addition, the upregulation of MHC-I and MHC-II expression was inhibited by an adenosine P1 receptor antagonist and by inhibitors of CD39 and CD73, which metabolize ATP to adenosine. These results suggest that adenosine is required for the ATP-induced upregulation of MHC-I and MHC-II. In the mixed leukocyte reaction assay, ATP-stimulated BMDCs activated CD4 and CD8T cells and induced interferon-gamma (IFN-gamma) production by these T cells. Collectively, these results suggest that high concentrations of extracellular ATP upregulate the expression of antigenpresenting and co-stimulatory molecules but not that of coinhibitory molecules in BMDCs. Cooperative stimulation of ATP and its metabolite adenosine was required for the upregulation of MHC-I and MHC-II. These ATP-stimulated BMDCs induced the activation of IFN-gamma-producing T cells upon antigen presentation. en-copyright= kn-copyright= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnishiHiroka en-aut-sei=Onishi en-aut-mei=Hiroka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkadaYuki en-aut-sei=Ikada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasakiKento en-aut-sei=Masaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaSatoshi en-aut-sei=Tanaka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry, and 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=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=5 article-no= start-page=390 end-page=405 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PARsylation-mediated ubiquitylation: lessons from rare hereditary disease Cherubism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Modification of proteins by ADP-ribose (PARsylation) is catalyzed by the poly(ADP-ribose) polymerase (PARP) family of enzymes exemplified by PARP1, which controls chromatin organization and DNA repair. Additionally, PARsylation induces ubiquitylation and proteasomal degradation of its substrates because PARsylation creates a recognition site for E3-ubiquitin ligase. The steady-state levels of the adaptor protein SH3-domain binding protein 2 (3BP2) is negatively regulated by tankyrase (PARP5), which coordinates ubiquitylation of 3BP2 by the E3-ligase ring finger protein 146 (RNF146). 3BP2 missense mutations uncouple 3BP2 from tankyrase-mediated negative regulation and cause Cherubism, an autosomal dominant autoinflammatory disorder associated with craniofacial dysmorphia. In this review, we summarize the diverse biological processes, including bone dynamics, metabolism, and Toll-like receptor (TLR) signaling controlled by tankyrase-mediated PARsylation of 3BP2, and highlight the therapeutic potential of this pathway. en-copyright= kn-copyright= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RottapelRobert en-aut-sei=Rottapel en-aut-mei=Robert kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil= kn-affil= en-keyword=PARsylation kn-keyword=PARsylation en-keyword=ubiquitylation kn-keyword=ubiquitylation en-keyword=proteasomal degradation kn-keyword=proteasomal degradation en-keyword=Cherubism kn-keyword=Cherubism en-keyword=tankyrase kn-keyword=tankyrase en-keyword=PARPs kn-keyword=PARPs END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=3 article-no= start-page=319 end-page=321 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cerebral Hypoperfusion Detected by Arterial Spine-Labelled MR Imaging in a Patient Presenting with Migraine and Panic Attacks en-subtitle= kn-subtitle= en-abstract= kn-abstract=I report a case of arterial spine-labelled MR imaging (ASL)-detected cerebral hypoperfusion during migraine and panic attacks. A 20-year-old woman with a history of headache for 6 years and independent panic attacks for 3 years was transferred to Okayama Kyokuto Hospital for panic attacks. On that day, she had had severe headache that was improved by taking non-steroidal anti-inflammatory drug, but panic attacks initiated. On arrival, she also complained of a mild headache. ASL revealed cerebral hypoperfusion in the right temporo-occipital region. The threshold to induce panic attacks in migraine patients could be lowered by the physiopathology underlying migraine attacks. en-copyright= kn-copyright= en-aut-name=KashiharaKenichi en-aut-sei=Kashihara en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama Kyokuto Hospital kn-affil= en-keyword=migraine kn-keyword=migraine en-keyword=panic attack kn-keyword=panic attack en-keyword=arterial spine-labelled magnetic resonance imaging kn-keyword=arterial spine-labelled magnetic resonance imaging en-keyword=aura kn-keyword=aura en-keyword=cortical spreading depression kn-keyword=cortical spreading depression END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=3 article-no= start-page=255 end-page=262 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Prevalence of Antimicrobial Resistance in Okayama from a National Database between 2018 and 2021 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Antimicrobial resistance is an emerging global threat that must be addressed using a multidisciplinary approach. This study aimed to raise awareness of high-level antimicrobial-resistant (AMR) pathogens in Japan by comparing their recent prevalences among prefectures, particularly Okayama. Data for the isolation proportions of meropenem-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae, and levofloxacin-resistant E. coli and K. pneumoniae were collected from the Japan Nosocomial Infections Surveillance, a national database sponsored by the Japanese Ministry of Health, Labour, and Welfare, between 2018 and 2021. The average isolated proportions of the seven AMR pathogens were higher in Okayama compared to other prefectures: the worst (19.9%) was meropenem-resistant P. aeruginosa, the sixth worst (57.2%) was methicillin-resistant S. aureus, the eighth worst (3.3%) was vancomycin-resistant E. faecium, the second (37.8%) and fifth worst (17.6%) were cefotaxime-resistant E. coli and K. pneumoniae, respectively, and the fourth (49.9%) and third worst (8.7%) were levofloxacin-resistant E. coli and K. pneumoniae, respectively. Our study highlights the notably high prevalences of representative AMR pathogens in Okayama, suggesting the need for fundamental infection prevention and control by healthcare professionals, promoting antimicrobial stewardship, and educating undergraduates and postgraduates in Okayama. en-copyright= kn-copyright= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UdaKazuhiro en-aut-sei=Uda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=antimicrobial stewardship kn-keyword=antimicrobial stewardship en-keyword=epidemiology kn-keyword=epidemiology en-keyword=infection prevention and control kn-keyword=infection prevention and control en-keyword=Japan Nosocomial Infections Surveillance kn-keyword=Japan Nosocomial Infections Surveillance END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230607 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Chemo-preventive effects and antitumorigenic mechanisms of beer and nonalcoholic beer toward 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the chemopreventive effects of beer, nonalcoholic beers (NABs), and beer-components (glycine betaine (GB)) on NNK-induced lung tumorigenesis in A/J mice, and the possible mechanisms underlying the antitumorigenic effects of beer, NABs, and beer-components. Beer, NABs, and GB reduced NNK-induced lung tumorigenesis. We investigated the antimutagenicity of beer, NABs and beer-components (GB and pseudouridine (PU)) toward the mutagenicity of 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Beer, NABs, and beer components were antimutagenic toward MNNG and NNK in the Ames test using S. typhimurium TA1535. In contrast, MNNG and NNK mutagenicity detected in S. typhimurium YG7108, a strain lacking O-6-methylguanine DNA methyltransferases (ogt(ST) and ada(ST)) did not decrease in the presence of beer, NABs, or beer components, suggesting that they may mediate its antimutagenic effect by enhancing DNA damage repair. Phosphorylation of Akt and STAT3, with or without epidermal growth factor stimulation, in lung epithelial-like A549 cells were significantly decreased following beer, NABs, GB and PU. They targeted both the initiation and growth/progression steps of carcinogenesis, specifically via antimutagenesis, stimulation of alkyl DNA-adduct repair, and suppression of Akt- and STAT3- mediated growth signaling. GB and PU may contribute, in part, to the biological effects of beer and NABs via the suppression of Akt and STAT3 phosphorylation. en-copyright= kn-copyright= en-aut-name=TakataJun en-aut-sei=Takata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirabaeAtsuko en-aut-sei=Hirabae en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Arimoto-KobayashiSakae en-aut-sei=Arimoto-Kobayashi en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Anti-mutagenesis kn-keyword=Anti-mutagenesis en-keyword=Signal transduction kn-keyword=Signal transduction en-keyword=Lung tumorigenesis kn-keyword=Lung tumorigenesis en-keyword=DNA methylation kn-keyword=DNA methylation en-keyword=Tobacco-specific nitrosamine kn-keyword=Tobacco-specific nitrosamine en-keyword=Glycine betaine kn-keyword=Glycine betaine END start-ver=1.4 cd-journal=joma no-vol=175 cd-vols= no-issue= article-no= start-page=105921 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Thioredoxin deficiency increases oxidative stress and causes bilateral symmetrical degeneration in rat midbrain en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thioredoxin, encoded by Txn1, acts as a critical antioxidant in the defense against oxidative stress by regulating the dithiol/disulfide balance of interacting proteins. The role of thioredoxin in the central nervous system (CNS) is largely unknown. A phenotype-driven study of N-ethyl-N-nitrosourea-mutated rats with wild-running seizures revealed the importance of Txn1 mutations in CNS degeneration. Genetic mapping identified Txn1-F54L in the epileptic rats. The insulin-reducing activity of Txn1-F54L was approximately one-third of that of the wild-type (WT). Bilateral symmetrical vacuolar degeneration in the midbrain, mainly in the thalamus and the inferior colliculus, was observed in the Txn1-F54L rats. The lesions displayed neuronal and oligodendrocytic cell death. Neurons in Txn1-F54L rats showed morphological changes in the mitochondria. Vacuolar degeneration peaked at five weeks of age, and spontaneous repair began at seven weeks. The TUNEL assay showed that fibroblasts derived from homozygotes were susceptible to cell death under oxidative stress. In five-week-old WT rats, energy metabolism in the thalamus was significantly higher than that in the cerebral cortex. In conclusion, in juvenile rats, Txn1 seems to play an essential role in reducing oxidative stress in the midbrains with high energy metabolism. 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=ImaiHirohiko en-aut-sei=Imai en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshidaSaeko en-aut-sei=Ishida en-aut-mei=Saeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyokuniShinya en-aut-sei=Toyokuni en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MashimoTomoji en-aut-sei=Mashimo en-aut-mei=Tomoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Systems Science, Kyoto University Graduate School of Informatics kn-affil= affil-num=4 en-affil=Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo kn-affil= en-keyword=Txn1 kn-keyword=Txn1 en-keyword=Thioredoxin kn-keyword=Thioredoxin en-keyword=Mitochondria kn-keyword=Mitochondria en-keyword=Vacuolar degeneration kn-keyword=Vacuolar degeneration en-keyword=Epilepsy kn-keyword=Epilepsy en-keyword=Oxidative stress kn-keyword=Oxidative stress END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=4 article-no= start-page=488 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230419 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recent Advances in Apical Periodontitis Treatment: A Narrative Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Apical periodontitis is an inflammatory response caused by pulp infection. It induces bone resorption in the apical and periapical regions of the tooth. The most conservative approach to treat this condition is nonsurgical endodontic treatment. However, clinical failure has been reported with this approach; thus, alternative procedures are required. This review highlights recent literature regarding advanced approaches for the treatment of apical periodontitis. Various therapies, including biological medications, antioxidants, specialized pro-resolving lipid mediators, and stem cell therapy, have been tested to increase the success rate of treatment for apical periodontitis. Some of these approaches remain in the in vivo phase of research, while others have just entered the translational research phase to validate clinical application. However, a detailed understanding of the molecular mechanisms that occur during development of the immunoinflammatory reaction in apical periodontitis remains unclear. The aim of this review was to summarize advanced approaches for the treatment of apical periodontitis. Further research can confirm the potential of these alternative nonsurgical endodontic treatment approaches. en-copyright= kn-copyright= en-aut-name=AriasZulema en-aut-sei=Arias en-aut-mei=Zulema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NizamiMohammed Zahedul Islam en-aut-sei=Nizami en-aut-mei=Mohammed Zahedul Islam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChenXiaoting en-aut-sei=Chen en-aut-mei=Xiaoting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChaiXinyi en-aut-sei=Chai en-aut-mei=Xinyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=XuBin en-aut-sei=Xu en-aut-mei=Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuangCanyan en-aut-sei=Kuang en-aut-mei=Canyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Prince Philip Dental Hospital kn-affil= affil-num=3 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=apical periodontitis kn-keyword=apical periodontitis en-keyword=contemporary approaches kn-keyword=contemporary approaches en-keyword=nonsurgical endodontic treatment kn-keyword=nonsurgical endodontic treatment en-keyword=immune inflammatory disease kn-keyword=immune inflammatory disease en-keyword=alternative treatments kn-keyword=alternative treatments END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=5 article-no= start-page=714 end-page=721 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Catalytic enantioselective nucleophilic desymmetrization of phosphonate esters en-subtitle= kn-subtitle= en-abstract= kn-abstract=Molecules that contain a stereogenic phosphorus atom are crucial to medicine, agrochemistry and catalysis. While methods are available for the selective construction of various chiral organophosphorus compounds, catalytic enantioselective approaches for their synthesis are far less common. Given the vastness of possible substituent combinations around a phosphorus atom, protocols for their preparation should also be divergent, providing facile access not only to one but to many classes of phosphorus compounds. Here we introduce a catalytic and enantioselective strategy for the preparation of an enantioenriched phosphorus(V) centre that can be diversified enantiospecifically to a wide range of biologically relevant phosphorus(V) compounds. The process, which involves an enantioselective nucleophilic substitution catalysed by a superbasic bifunctional iminophosphorane catalyst, can accommodate a wide range of carbon substituents at phosphorus. The resulting stable, yet versatile, synthetic intermediates can be combined with a multitude of medicinally relevant O-, N- and S-based nucleophiles. en-copyright= kn-copyright= en-aut-name=FormicaMichele en-aut-sei=Formica en-aut-mei=Michele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RogovaTatiana en-aut-sei=Rogova en-aut-mei=Tatiana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiHeyao en-aut-sei=Shi en-aut-mei=Heyao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaharaNaoto en-aut-sei=Sahara en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FerkoBranislav en-aut-sei=Ferko en-aut-mei=Branislav kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FarleyAlistair J. M. en-aut-sei=Farley en-aut-mei=Alistair J. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ChristensenKirsten E. en-aut-sei=Christensen en-aut-mei=Kirsten E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=DuarteFernanda en-aut-sei=Duarte en-aut-mei=Fernanda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamazakiKen en-aut-sei=Yamazaki en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=DixonDarren J. en-aut-sei=Dixon en-aut-mei=Darren J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Chemistry Research Laboratory, Department of Chemistry, University of Oxford kn-affil= affil-num=2 en-affil=Chemistry Research Laboratory, Department of Chemistry, University of Oxford kn-affil= affil-num=3 en-affil=Chemistry Research Laboratory, Department of Chemistry, University of Oxford kn-affil= affil-num=4 en-affil=Chemistry Research Laboratory, Department of Chemistry, University of Oxford kn-affil= affil-num=5 en-affil=Chemistry Research Laboratory, Department of Chemistry, University of Oxford kn-affil= affil-num=6 en-affil=Chemistry Research Laboratory, Department of Chemistry, University of Oxford kn-affil= affil-num=7 en-affil=Chemistry Research Laboratory, Department of Chemistry, University of Oxford kn-affil= affil-num=8 en-affil=Chemistry Research Laboratory, Department of Chemistry, University of Oxford kn-affil= affil-num=9 en-affil=Division of Applied Chemistry, Okayama University kn-affil= affil-num=10 en-affil=Chemistry Research Laboratory, Department of Chemistry, University of Oxford kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=3 article-no= start-page=522 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Genotypic and Phenotypic Characteristics Contributing to Flomoxef Sensitivity in Clinical Isolates of ESBL-Producing E. coli Strains from Urinary Tract Infections en-subtitle= kn-subtitle= en-abstract= kn-abstract=We carried out a molecular biological analysis of extended-spectrum beta-lactamase (ESBL)-producing E. coli strains and their sensitivity to flomoxef (FMOX). Sequence type (ST) analysis by multilocus sequence typing (MLST) and classification of ESBL genotypes by multiplex PCR were performed on ESBL-producing E. coli strains isolated from urine samples collected from patients treated at our institution between 2008 and 2018. These sequences were compared with results for antimicrobial drug susceptibility determined using a micro-liquid dilution method. We also analyzed cases treated with FMOX at our institution to examine its clinical efficacy. Of the 911 E. coli strains identified, 158 (17.3%) were ESBL-producing. Of these, 67.7% (107/158) were strain ST-131 in ST analysis. Nearly all (154/158; 97.5%) were CTX-M genotypes, with M-14 and M-27 predominating. The isolated strains were sensitive to FMOX in drug susceptibility tests. Among the patient samples, 33 cases received FMOX, and of these, 5 had ESBL-producing E. coli. Among these five cases, three received FMOX for surgical prophylaxis as urinary carriers of ESBL-producing E. coli, and postoperative infections were prevented in all three patients. The other two patients received FMOX treatment for urinary tract infections. FMOX treatment was successful for one, and the other was switched to carbapenem. Our results suggest that FMOX has efficacy for perioperative prophylactic administration in urologic surgery involving carriers of ESBL-producing bacteria and for therapeutic administration for urinary tract infections. Use of FMOX avoids over-reliance on carbapenems or beta-lactamase inhibitors and thus is an effective antimicrobial countermeasure. en-copyright= kn-copyright= en-aut-name=SakaedaKazuma en-aut-sei=Sakaeda en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaruyamaYuki en-aut-sei=Maruyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WadaKoichiro en-aut-sei=Wada en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Koichiro Wada Department of Urology, School of Medicine, Shimane University kn-affil= affil-num=7 en-affil=Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=antimicrobial resistance kn-keyword=antimicrobial resistance en-keyword=Escherichia coli kn-keyword=Escherichia coli en-keyword=urinary tract infections kn-keyword=urinary tract infections en-keyword=flomoxef kn-keyword=flomoxef en-keyword=ST131 kn-keyword=ST131 END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=5 article-no= start-page=4996 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SPRED2: A Novel Regulator of Epithelial-Mesenchymal Transition and Stemness in Hepatocellular Carcinoma Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The downregulation of SPRED2, a negative regulator of the ERK1/2 pathway, was previously detected in human cancers; however, the biological consequence remains unknown. Here, we investigated the effects of SPRED2 loss on hepatocellular carcinoma (HCC) cell function. Human HCC cell lines, expressing various levels of SPRED2 and SPRED2 knockdown, increased ERK1/2 activation. SPRED2-knockout (KO)-HepG2 cells displayed an elongated spindle shape with increased cell migration/invasion and cadherin switching, with features of epithelial-mesenchymal transition (EMT). SPRED2-KO cells demonstrated a higher ability to form spheres and colonies, expressed higher levels of stemness markers and were more resistant to cisplatin. Interestingly, SPRED2-KO cells also expressed higher levels of the stem cell surface markers CD44 and CD90. When CD44(+)CD90(+) and CD44(-)CD90(-) populations from WT cells were analyzed, a lower level of SPRED2 and higher levels of stem cell markers were detected in CD44(+)CD90(+) cells. Further, endogenous SPRED2 expression decreased when WT cells were cultured in 3D, but was restored in 2D culture. Finally, the levels of SPRED2 in clinical HCC tissues were significantly lower than those in adjacent non-HCC tissues and were negatively associated with progression-free survival. Thus, the downregulation of SPRED2 in HCC promotes EMT and stemness through the activation of the ERK1/2 pathway, and leads to more malignant phenotypes. en-copyright= kn-copyright= en-aut-name=GaoTong en-aut-sei=Gao en-aut-mei=Tong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YangXu en-aut-sei=Yang en-aut-mei=Xu 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=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangTianyi en-aut-sei=Wang en-aut-mei=Tianyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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 Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, 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 Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cell Biology, 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= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cancer stem cells kn-keyword=cancer stem cells en-keyword=epithelial-mesenchymal transition kn-keyword=epithelial-mesenchymal transition en-keyword=ERK1/2-MAPK kn-keyword=ERK1/2-MAPK en-keyword=tumorigenesis kn-keyword=tumorigenesis END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=90 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Autophagy as a potential mechanism underlying the biological effect of 1,25-Dihydroxyvitamin D3 on periodontitis: a narrative review en-subtitle= kn-subtitle= en-abstract= kn-abstract=The major active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is known for its wide bioactivity in periodontal tissues. Although the exact mechanisms underlying its protective action against periodontitis remain unclear, recent studies have shown that 1,25D3 regulates autophagy. Autophagy is vital for intracellular pathogen invasion control, inflammation regulation, and bone metabolic balance in periodontal tissue homeostasis, and its regulation could be an interesting pathway for future periodontal studies. Since vitamin D deficiency is a worldwide health problem, its role as a potential regulator of autophagy provides new insights into periodontal diseases. Based on this premise, this narrative literature review aimed to investigate the possible connection between 1,25D3 and autophagy in periodontitis. A comprehensive literature search was conducted on PubMed using the following keywords (e.g., vitamin D, autophagy, periodontitis, pathogens, epithelial cells, immunity, inflammation, and bone loss). In this review, the latest studies on the protective action of 1,25D3 against periodontitis and the regulation of autophagy by 1,25D3 are summarized, and the potential role of 1,25D3-activated autophagy in the pathogenesis of periodontitis is analyzed. 1,25D3 can exert a protective effect against periodontitis through different signaling pathways in the pathogenesis of periodontitis, and at least part of this regulatory effect is achieved through the activation of the autophagic response. This review will help clarify the relationship between 1,25D3 and autophagy in the homeostasis of periodontal tissues and provide perspectives for researchers to optimize prevention and treatment strategies in the future. en-copyright= kn-copyright= en-aut-name=ChenXiaoting en-aut-sei=Chen en-aut-mei=Xiaoting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AriasZulema en-aut-sei=Arias en-aut-mei=Zulema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Periodontics and Endodontics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathophysiology?Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Vitamin D kn-keyword=Vitamin D en-keyword=Autophagy kn-keyword=Autophagy en-keyword=Periodontitis kn-keyword=Periodontitis en-keyword=Epithelial barrier kn-keyword=Epithelial barrier en-keyword=Immunity kn-keyword=Immunity en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Alveolar bone loss kn-keyword=Alveolar bone loss END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=1 article-no= start-page=65 end-page=70 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of a Cyclooxygenase-2 Inhibitor in Combination with (?)-Epigallocatechin Gallate or Polyphenon E on Cisplatin-Induced Lung Tumorigenesis in A/J Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the effects of celecoxib combined with (?)-epigallocatechin-3-gallate (EGCG) or polyphenon E in a cisplatin-induced lung tumorigenesis model. Four-week-old female A/J mice were divided into seven groups: (i) Control, (ii) 150 mg/kg celecoxib (150Cel), (iii) 1,500 mg/kg celecoxib (1500Cel), (iv) EGCG+150 mg/kg celecoxib (EGCG+150Cel), (v) EGCG+1,500 mg/kg celecoxib (EGCG+1500Cel), (vi) polyphenon E+150 mg/kg celecoxib (PolyE+150Cel), and (vii) polyphenon E+1,500 mg/kg celecoxib (PolyE+1500Cel). All mice were administered cisplatin (1.62 mg/kg of body weight, i.p.) 1×/week for 10 weeks and sacrificed at week 30; the numbers of tumors on the lung surface were then determined. The tumor incidence and multiplicity (no. of tumors/mouse, mean±SD) were respectively 95% and 2.15±1.50 in Control, 95% and 2.10±1.29 in 150Cel, 86% and 1.67±1.20 in 1500Cel, 71% and 1.38±1.24 in EGCG+150Cel, 67% and 1.29±1.38 in EGCG+1500Cel, 80% and 1.95±1.36 in PolyE+150Cel, and 65% and 1.05±0.10 in PolyE+1500Cel. The combination of high-dose celecoxib with EGCG or polyphenon E significantly reduced multiplicity in cisplatin-induced lung tumors. en-copyright= kn-copyright= en-aut-name=SatoKen en-aut-sei=Sato en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakigawaNagio en-aut-sei=Takigawa en-aut-mei=Nagio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatayamaHideki en-aut-sei=Katayama en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KishinoDaizo en-aut-sei=Kishino en-aut-mei=Daizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkadaToshiaki en-aut-sei=Okada en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HisamotoAkiko en-aut-sei=Hisamoto en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MimotoJunko en-aut-sei=Mimoto en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UeokaHiroshi en-aut-sei=Ueoka en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TanimotoMitsune en-aut-sei=Tanimoto en-aut-mei=Mitsune kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaedaYoshionobu en-aut-sei=Maeda en-aut-mei=Yoshionobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Internal Medicine 4, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medicine, Yamaguchi-Ube Medical Center kn-affil= affil-num=5 en-affil=Department of Medicine, Yamaguchi-Ube Medical Center kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Internal Medicine 4, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Medicine, Yamaguchi-Ube Medical Center kn-affil= affil-num=12 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=celecoxib kn-keyword=celecoxib en-keyword=cisplatin kn-keyword=cisplatin en-keyword=EGCG kn-keyword=EGCG en-keyword=lung tumor kn-keyword=lung tumor en-keyword=polyphenon E kn-keyword=polyphenon E END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=110 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Extracellular Vesicles: New Classification and Tumor Immunosuppression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Simple Summary Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles that carry bioactive molecules and deliver them to recipient cells. Classical EVs are exosomes, microvesicles, and apoptotic bodies. This review classifies classical and additional EV types, including autophagic EVs, matrix vesicles, and stressed EVs. Of note, matrix vesicles are key components interacting with extracellular matrices (ECM) in the tumor microenvironment. We also review how EVs are involved in the communication between cancer cells and tumor-associated cells (TAC), leading to establishing immunosuppressive and chemoresistant microenvironments. These include cancer-associated fibroblasts (CAF), mesenchymal stem cells (MSC), blood endothelial cells (BEC), lymph endothelial cells (LEC), and immune cells, such as tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), dendritic cells, natural killer cells, killer T cells, and immunosuppressive cells, such as regulatory T cells and myeloid-derived suppressor cells (MDSC). Exosomal long noncoding RNA (lncRNA), microRNA, circular RNA, piRNA, mRNA, and proteins are crucial in communication between cancer cells and TACs for establishing cold tumors. Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles carrying various types of molecules. These EV cargoes are often used as pathophysiological biomarkers and delivered to recipient cells whose fates are often altered in local and distant tissues. Classical EVs are exosomes, microvesicles, and apoptotic bodies, while recent studies discovered autophagic EVs, stressed EVs, and matrix vesicles. Here, we classify classical and new EVs and non-EV nanoparticles. We also review EVs-mediated intercellular communication between cancer cells and various types of tumor-associated cells, such as cancer-associated fibroblasts, adipocytes, blood vessels, lymphatic vessels, and immune cells. Of note, cancer EVs play crucial roles in immunosuppression, immune evasion, and immunotherapy resistance. Thus, cancer EVs change hot tumors into cold ones. Moreover, cancer EVs affect nonimmune cells to promote cellular transformation, including epithelial-to-mesenchymal transition (EMT), chemoresistance, tumor matrix production, destruction of biological barriers, angiogenesis, lymphangiogenesis, and metastatic niche formation. en-copyright= kn-copyright= en-aut-name=ShetaMona en-aut-sei=Sheta en-aut-mei=Mona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TahaEman A. en-aut-sei=Taha en-aut-mei=Eman A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LuYanyin en-aut-sei=Lu en-aut-mei=Yanyin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Biochemistry, Faculty of Science, Ain Shams University kn-affil= affil-num=3 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=extracellular vesicle kn-keyword=extracellular vesicle en-keyword=exosome kn-keyword=exosome en-keyword=autophagy kn-keyword=autophagy en-keyword=amphisome kn-keyword=amphisome en-keyword=matrix vesicle kn-keyword=matrix vesicle en-keyword=cellular communication kn-keyword=cellular communication en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=immunosuppression kn-keyword=immunosuppression en-keyword=immune evasion kn-keyword=immune evasion en-keyword=therapy resistance kn-keyword=therapy resistance END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=822 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230103 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cycloartenyl Ferulate Is the Predominant Compound in Brown Rice Conferring Cytoprotective Potential against Oxidative Stress-Induced Cytotoxicity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Since brown rice extract is a rich source of biologically active compounds, the present study is aimed to quantify the major compounds in brown rice and to compare their cytoprotective potential against oxidative stress. The content of the main hydrophobic compounds in brown rice followed the order of cycloartenyl ferulate (CAF) (89.00 +/- 8.07 nmol/g) >> alpha-tocopherol (alpha T) (19.73 +/- 2.28 nmol/g) > gamma-tocotrienol (gamma T3) (18.24 +/- 1.41 nmol/g) > alpha-tocotrienol (alpha T3) (16.02 +/- 1.29 nmol/g) > gamma-tocopherol (gamma T) (3.81 +/- 0.40 nmol/g). However, the percent contribution of CAF to the radical scavenging activity of one gram of whole brown rice was similar to those of alpha T, alpha T3, and gamma T3 because of its weaker antioxidant activity. The CAF pretreatment displayed a significant cytoprotective effect on the hydrogen peroxide-induced cytotoxicity from 10 mu M, which is lower than the minimal concentrations of alpha T and gamma T required for a significant protection. CAF also enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation coincided with the enhancement of the heme oxygenase-1 (HO-1) mRNA level. An HO-1 inhibitor, tin protoporphyrin IX (SnPP), significantly impaired the cytoprotection of CAF. The cytoprotective potential of CAF is attributable to its cycloartenyl moiety besides the ferulyl moiety. These results suggested that CAF is the predominant cytoprotector in brown rice against hydrogen peroxide-induced cytotoxicity. en-copyright= kn-copyright= en-aut-name=WuHongyan en-aut-sei=Wu en-aut-mei=Hongyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraToshiyuki en-aut-sei=Nakamura en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GuoYingnan en-aut-sei=Guo en-aut-mei=Yingnan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoRiho en-aut-sei=Matsumoto en-aut-mei=Riho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MunemasaShintaro en-aut-sei=Munemasa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=School of Food Science and Technology, Dalian Polytechnic University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=School of Food Science and Technology, Dalian Polytechnic University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=cycloartenyl ferulate kn-keyword=cycloartenyl ferulate en-keyword=antioxidative effect kn-keyword=antioxidative effect en-keyword=cytoprotective potential kn-keyword=cytoprotective potential en-keyword=heme oxygenase-1 kn-keyword=heme oxygenase-1 en-keyword=nuclear factor erythroid 2-related factor 2 kn-keyword=nuclear factor erythroid 2-related factor 2 END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=50 article-no= start-page=46573 end-page=46582 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oligoarginine-Conjugated Peptide Foldamers Inhibiting Vitamin D Receptor-Mediated Transcription en-subtitle= kn-subtitle= en-abstract= kn-abstract=The vitamin D receptor (VDR) is a nuclear receptor, which is involved in several physiological processes, including differentiation and bone homeostasis. The VDR is a promising target for the development of drugs against cancer and bone-related diseases. To date, several VDR antagonists, which bind to the ligand binding domain of the VDR and compete with the endogenous agonist 1 alpha,25(OH)D3, have been reported. However, these ligands contain a secosteroidal skeleton, which is chemically unstable and complicated to synthesize. A few VDR antagonists with a nonsecosteroidal skeleton have been reported. Alternative inhibitors against VDR transactivation that act via different mechanisms are desirable. Here, we developed peptide-based VDR inhibitors capable of disrupting the VDR-coactivator interaction. It was reported that helical SRC2-3 peptides strongly bound to the VDR and competed with the coactivator in vitro. Therefore, we designed and synthesized a series of SRC2-3 derivatives by the introduction of nonproteinogenic amino acids, such as beta-amino acids, and by side-chain stapling to stabilize helical structures and provide resistance against digestive enzymes. In addition, conjugation with a cell-penetrating peptide increased the cell membrane permeability and was a promising strategy for intracellular VDR inhibition. The nona-arginine-conjugated peptides 24 with side-chain stapling and 25 with cyclic beta-amino acids showed strong intracellular VDR inhibitory activity, resulting in suppression of the target gene expression and inhibition of the cell differentiation of HL-60 cells. Herein, the peptide design, structure-activity relationship (SAR) study, and biological evaluation of the peptides are described. en-copyright= kn-copyright= en-aut-name=TakyoMami en-aut-sei=Takyo en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoYumi en-aut-sei=Sato en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirataNaoya en-aut-sei=Hirata en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuchiyaKeisuke en-aut-sei=Tsuchiya en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshidaHiroaki en-aut-sei=Ishida en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuroharaTakashi en-aut-sei=Kurohara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YanaseYuta en-aut-sei=Yanase en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItoTakahito en-aut-sei=Ito en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KandaYasunari en-aut-sei=Kanda en-aut-mei=Yasunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoKeiko en-aut-sei=Yamamoto en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MisawaTakashi en-aut-sei=Misawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DemizuYosuke en-aut-sei=Demizu en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=National Institute of Health Sciences kn-affil= affil-num=2 en-affil=National Institute of Health Sciences kn-affil= affil-num=3 en-affil=National Institute of Health Sciences kn-affil= affil-num=4 en-affil=National Institute of Health Sciences kn-affil= affil-num=5 en-affil=Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University kn-affil= affil-num=6 en-affil=National Institute of Health Sciences kn-affil= affil-num=7 en-affil=National Institute of Health Sciences kn-affil= affil-num=8 en-affil=National Institute of Health Sciences kn-affil= affil-num=9 en-affil=National Institute of Health Sciences kn-affil= affil-num=10 en-affil=Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University kn-affil= affil-num=11 en-affil=National Institute of Health Sciences kn-affil= affil-num=12 en-affil=National Institute of Health Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=298 cd-vols= no-issue=12 article-no= start-page=102668 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Crystal structures of photosystem II from a cyanobacterium expressing psbA2 in comparison to psbA3 reveal differences in the D1 subunit en-subtitle= kn-subtitle= en-abstract= kn-abstract=Three psbA genes (psbA1, psbA2, and psbA3) encoding the D1 subunit of photosystem II (PSII) are present in the ther-mophilic cyanobacterium Thermosynechococcus elongatus and are expressed differently in response to changes in the growth environment. To clarify the functional differences of the D1 protein expressed from these psbA genes, PSII dimers from two strains, each expressing only one psbA gene (psbA2 or psbA3), were crystallized, and we analyzed their structures at resolu-tions comparable to previously studied PsbA1-PSII. Our results showed that the hydrogen bond between pheophytin/D1 (PheoD1) and D1-130 became stronger in PsbA2-and PsbA3-PSII due to change of Gln to Glu, which partially explains the increase in the redox potential of PheoD1 observed in PsbA3. In PsbA2, one hydrogen bond was lost in PheoD1 due to the change of D1-Y147F, which may explain the decrease in stability of PheoD1 in PsbA2. Two water molecules in the Cl-1 channel were lost in PsbA2 due to the change of D1-P173M, leading to the narrowing of the channel, which may explain the lower efficiency of the S-state transition beyond S2 in PsbA2-PSII. In PsbA3-PSII, a hydrogen bond between D1-Ser270 and a sulfoquinovosyl-diacylglycerol molecule near QB dis-appeared due to the change of D1-Ser270 in PsbA1 and PsbA2 to D1-Ala270. This may result in an easier exchange of bound QB with free plastoquinone, hence an enhancement of oxygen evolution in PsbA3-PSII due to its high QB exchange efficiency. These results provide a structural basis for further functional examination of the three PsbA variants. en-copyright= kn-copyright= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Ugai-AmoNatsumi en-aut-sei=Ugai-Amo en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ToneNaoki en-aut-sei=Tone en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakagawaAkiko en-aut-sei=Nakagawa en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwaiMasako en-aut-sei=Iwai en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IkeuchiMasahiko en-aut-sei=Ikeuchi en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugiuraMiwa en-aut-sei=Sugiura en-aut-mei=Miwa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugaMichihiro en-aut-sei=Suga en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Jian-RenShen en-aut-sei=Jian-Ren en-aut-mei=Shen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, 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=Proteo-Science Research Center, Ehime University kn-affil= affil-num=5 en-affil=Graduate School and College of Arts and Sciences, The University of Tokyo kn-affil= affil-num=6 en-affil=Graduate School and College of Arts and Sciences, The University of Tokyo kn-affil= affil-num=7 en-affil=Proteo-Science Research Center, Ehime University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=9 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=1 article-no= start-page=26 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Chemopreventive effects and anti-tumorigenic mechanisms of Actinidia arguta, known as sarunashi in Japan toward 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)- induced lung tumorigenesis in a/J mouse en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Previously, we reported the inhibitory effect of Actinidia arguta juice, known as sarunashi juice (sar-j) in Japan, on mutagenesis, inflammation, and mouse skin tumorigenesis. The components of A. arguta responsible for the anti-mutagenic effects were identified to be water-soluble, heat-labile phenolic compounds. We proposed isoquercetin (isoQ) as a candidate anticarcinogenic component. In this study, we sought to investigate the chemopreventive effects of A. arguta juice and isoQ on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice, and identify the possible mechanisms underlying the anti-tumorigenic effects of A. arguta.

Results
The number of tumor nodules per mouse lung in the group injected with NNK and administered A. arguta juice orally was significantly lower than that in the group injected with NNK only. Oral administration of isoQ also reduced the number of nodules in the mouse lungs. As expected, the mutagenicity of NNK and 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) detected using S. typhimurium TA1535 decreased in the presence of sar-j. However, NNK and MNNG mutagenicity detected using S. typhimurium YG7108, a strain lacking the O6-methylguanine DNA methyltransferases (ogtST and adaST) did not decrease in the presence of sar-j suggesting that sar-j may mediate its antimutagenic effect by enhancing the DNA damage repair by ogtST and adaST. Phosphorylation of Akt, with or without epidermal growth factor stimulation, in A549 cells was significantly decreased following sar-j and isoQ treatment, indicating that components in sar-j including isoQ suppressed the PI3K/AKT signaling pathways.

Conclusions
Sar-j and isoQ reduced NNK-induced lung tumorigenesis. Sar-j targets both the initiation and growth/progression steps during carcinogenesis, specifically via anti-mutagenesis, stimulation of alkyl DNA adduct repair, and suppression of Akt-mediated growth signaling. IsoQ might contribute in part to the biological effects of sar-j via suppression of Akt phosphorylation, but it may not be the main active ingredient. en-copyright= kn-copyright= en-aut-name=TakataJun en-aut-sei=Takata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyakeNaoko en-aut-sei=Miyake en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaikiYusuke en-aut-sei=Saiki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TadaMisako en-aut-sei=Tada en-aut-mei=Misako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasakiKensuke en-aut-sei=Sasaki en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Arimoto-KobayashiSakae en-aut-sei=Arimoto-Kobayashi en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Akt signal transduction kn-keyword=Akt signal transduction en-keyword=Lung tumorigenesis kn-keyword=Lung tumorigenesis en-keyword=Anti-mutagenesis kn-keyword=Anti-mutagenesis en-keyword=DNA methylation kn-keyword=DNA methylation en-keyword=Tobacco-specific nitrosamine kn-keyword=Tobacco-specific nitrosamine en-keyword=Isoquercetin kn-keyword=Isoquercetin END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=19458 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Defect-free and crystallinity-preserving ductile deformation in semiconducting Ag2S en-subtitle= kn-subtitle= en-abstract= kn-abstract=Typical ductile materials are metals, which deform by the motion of defects like dislocations in association with non-directional metallic bonds. Unfortunately, this textbook mechanism does not operate in most inorganic semiconductors at ambient temperature, thus severely limiting the development of much-needed flexible electronic devices. We found a shear-deformation mechanism in a recently discovered ductile semiconductor, monoclinic-silver sulfide (Ag2S), which is defect-free, omni-directional, and preserving perfect crystallinity. Our first-principles molecular dynamics simulations elucidate the ductile deformation mechanism in monoclinic-Ag2S under six types of shear systems. Planer mass movement of sulfur atoms plays an important role for the remarkable structural recovery of sulfur-sublattice. This in turn arises from a distinctively high symmetry of the anion-sublattice in Ag2S, which is not seen in other brittle silver chalcogenides. Such mechanistic and lattice-symmetric understanding provides a guideline for designing even higher-performance ductile inorganic semiconductors. en-copyright= kn-copyright= en-aut-name=MisawaMasaaki en-aut-sei=Misawa en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HokyoHinata en-aut-sei=Hokyo en-aut-mei=Hinata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaShogo en-aut-sei=Fukushima en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimamuraKohei en-aut-sei=Shimamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KouraAkihide en-aut-sei=Koura en-aut-mei=Akihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimojoFuyuki en-aut-sei=Shimojo en-aut-mei=Fuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KaliaRajiv K. en-aut-sei=Kalia en-aut-mei=Rajiv K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoAiichiro en-aut-sei=Nakano en-aut-mei=Aiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=VashishtaPriya en-aut-sei=Vashishta en-aut-mei=Priya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Faculty of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Physics, Kumamoto University kn-affil= affil-num=3 en-affil=Department of Physics, Kumamoto University kn-affil= affil-num=4 en-affil=Department of Physics, Kumamoto University kn-affil= affil-num=5 en-affil=Department of Physics, Kumamoto University kn-affil= affil-num=6 en-affil=Department of Physics, Kumamoto University kn-affil= affil-num=7 en-affil=Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, Department of Computer Science, Department of Chemical Engineering and Materials Science, and Department of Biological Science, University of Southern California kn-affil= affil-num=8 en-affil=Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, Department of Computer Science, Department of Chemical Engineering and Materials Science, and Department of Biological Science, University of Southern California kn-affil= affil-num=9 en-affil=Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, Department of Computer Science, Department of Chemical Engineering and Materials Science, and Department of Biological Science, University of Southern California kn-affil= END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=5 article-no= start-page=643 end-page=651 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Optical collection of extracellular vesicles in a culture medium enhanced by interactions with gold nanoparticles en-subtitle= kn-subtitle= en-abstract= kn-abstract=Extracellular vesicles (EVs) exist in biological fluids such as blood, urine, and cerebrospinal fluid and are promising cancer biomarkers. Attempts to isolate and analyze trace EVs, however, have been a challenge for researchers studying their functions and secretion mechanisms, which has stymied the options for diagnostic application. This study demonstrated a collection of EVs that was enhanced by gold nanoparticles (AuNPs) via the use of optical force. The collection system consists of an inverted microscope equipped with a CCD camera, a square capillary connected with a PTFE tube, and an Nd:YAG laser that generates optical force. The laser beam was focused on a capillary wall in which a cell culture medium containing EVs flowed continuously. Control of the surface charges on both the capillary wall and the AuNPs achieved the collection and retention of EVs on the capillary wall. The positively charged capillary wall retained EVs even after the laser irradiation was halted due to the negative charges inherent on the surface of EVs. Conversely, positively charged AuNPs had a strong electrostatic interaction with EVs and enhanced the optical force acting on them, which made collecting them a much more efficient process. en-copyright= kn-copyright= en-aut-name=TaniYumeki en-aut-sei=Tani en-aut-mei=Yumeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OchiaiKenta en-aut-sei=Ochiai en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanetaTakashi en-aut-sei=Kaneta en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Okayama University kn-affil= en-keyword=Optical force kn-keyword=Optical force en-keyword=Extracellular vesicle kn-keyword=Extracellular vesicle en-keyword=exosome kn-keyword=exosome en-keyword=Gold nanoparticle kn-keyword=Gold nanoparticle en-keyword=Optical trapping kn-keyword=Optical trapping END start-ver=1.4 cd-journal=joma no-vol=289 cd-vols= no-issue=1985 article-no= start-page=20221126 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221019 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Footedness for scratching itchy eyes in rodents en-subtitle= kn-subtitle= en-abstract= kn-abstract=The neural bases of itchy eye transmission remain unclear compared with those involved in body itch. Here, we show in rodents that the gastrin-releasing peptide receptor (GRPR) of the trigeminal sensory system is involved in the transmission of itchy eyes. Interestingly, we further demonstrate a difference in scratching behaviour between the left and right hindfeet in rodents; histamine instillation into the conjunctival sac of both eyes revealed right-foot biased laterality in the scratching movements. Unilateral histamine instillation specifically induced neural activation in the ipsilateral sensory pathway, with no significant difference between the activations following left- and right-eye instillations. Thus, the behavioural laterality is presumably due to right-foot preference in rodents. Genetically modified rats with specific depletion of Grpr-expressing neurons in the trigeminal sensory nucleus caudalis of the medulla oblongata exhibited fewer and shorter histamine-induced scratching movements than controls and eliminated the footedness. These results taken together indicate that the Grp-expressing neurons are required for the transmission of itch sensation from the eyes, but that foot preference is generated centrally. These findings could open up a new field of research on the mechanisms of the laterality in vertebrates and also offer new potential therapeutic approaches to refractory pruritic eye disorders. en-copyright= kn-copyright= en-aut-name=KatayamaYukitoshi en-aut-sei=Katayama en-aut-mei=Yukitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiuraAyane en-aut-sei=Miura en-aut-mei=Ayane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakamotoTatsuya en-aut-sei=Sakamoto en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakanamiKeiko en-aut-sei=Takanami en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoHirotaka en-aut-sei=Sakamoto en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi kn-affil= affil-num=2 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi kn-affil= affil-num=3 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi kn-affil= affil-num=4 en-affil=Mouse Genomics Resources Laboratory, National Institute of Genetics, Yata, Mishima kn-affil= affil-num=5 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi kn-affil= en-keyword=itchy eyes kn-keyword=itchy eyes en-keyword=histamine kn-keyword=histamine en-keyword=gastrin-releasing peptide receptor kn-keyword=gastrin-releasing peptide receptor en-keyword=footedness kn-keyword=footedness END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=6 article-no= start-page=715 end-page=721 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Graphene Oxide-based Endodontic Sealer: An in Vitro Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The failure of endodontic treatment is directly associated with microbial infection in the root canal or periapical areas. An endodontic sealer that is both bactericidal and biocompatible is essential for the success of root canal treatments. This is one of the vital issues yet to be solved in clinical dental practice. This in vitro study assessed the effectiveness of graphene oxide (GO) composites GO-CaF2 and GO-Ag-CaF2 as endodontic sealer materials. Dentin slices were coated with either the GO-based composites or commonly used root canal sealers (non-eugenol zinc oxide sealer). The coated slices were treated in 0.9% NaCl, phosphate-buffered saline (PBS), and simulated body fluid (SBF) at 37?C for 24 hours to compare their sealing effect on the dentin surface. In addition, the radiopacity of these composites was examined to assess whether they complied with the requirements of a sealer for good radiographic visualization. Scanning electron microscopy showed the significant sealing capability of the composites as coating materials. Radiographic images confirmed their radiopacity. Mineral deposition indicated their bioactivity, especially of GO-Ag-CaF2, and thus it is potential for regenerative application. They were both previously shown to be bactericidal to oral microbes and cytocompatible with host cells. With such a unique assemblage of critical properties, these GO-based composites show promise as endodontic sealers for protection against reinfection in root canal treatment and enhanced success in endodontic treatment overall. en-copyright= kn-copyright= en-aut-name=Mohammed Zahedul Islam Nizami en-aut-sei=Mohammed Zahedul Islam Nizami en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GorduysusMelahat en-aut-sei=Gorduysus en-aut-mei=Melahat kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AriasZulema en-aut-sei=Arias en-aut-mei=Zulema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pathophysiology ? Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology ? Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathophysiology ? Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathophysiology ? Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Research Core for Interdisciplinary Sciences, Okayama University kn-affil= affil-num=6 en-affil=Research Core for Interdisciplinary Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathophysiology ? Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=bioactive sealer kn-keyword=bioactive sealer en-keyword=graphene oxide kn-keyword=graphene oxide en-keyword=mineral deposition kn-keyword=mineral deposition en-keyword=antimicrobial activity kn-keyword=antimicrobial activity en-keyword=radiopacity kn-keyword=radiopacity END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=6 article-no= start-page=645 end-page=650 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fetal Cerebellar Growth Curves Based on Biomathematics in Normally Developing Japanese Fetuses and Fetuses with Trisomy 18 en-subtitle= kn-subtitle= en-abstract= kn-abstract=We used biomathematics to describe and compare cerebellar growth in normally developing and trisomy 18 Japanese fetuses. This retrospective study included 407 singleton pregnancies with fetuses at 14-39 weeks of gestation and 33 fetuses with trisomy 18 at 17-35 weeks. We used ultrasonography to measure fetal transverse cerebellar diameter (TCD) and anteroposterior cerebellar diameter (APCD). We hypothesized that cerebellar growth is proportional to cerebellar length at any given time point. We determined the formula L(t) ≒Keat+r, where e is Napier’s number, t is time, L is cerebellar length, and a, K, and r are constants. We then obtained regression functions for each TCD and APCD in all fetuses. The regression equations for TCD and APCD values in normal fetuses, expressed as exponential functions, were TCD(t)=27.85e0.02788t?28.62 (mm) (adjusted R2=0.997), and APCD(t)=324.29e0.00286t?322.62 (mm) (adjusted R2=0.995). These functions indicated that TCD and APCD grew at constant rates of 2.788%/week and 0.286%/week, respectively, throughout gestation. TCD (0.0153%/week) and APCD (0.000430%/week) grew more slowly in trisomy 18 fetuses. This study demonstrates the potential of biomathematics in clinical research and may aid in biological understanding of fetal cerebellar growth. en-copyright= kn-copyright= en-aut-name=TadaKatsuhiko en-aut-sei=Tada en-aut-mei=Katsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyagiYasunari en-aut-sei=Miyagi en-aut-mei=Yasunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KomatsuReina en-aut-sei=Komatsu en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkimotoNaoki en-aut-sei=Okimoto en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsukaharaSaya en-aut-sei=Tsukahara en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TateishiYoko en-aut-sei=Tateishi en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OokaNaomi en-aut-sei=Ooka en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaMizuho en-aut-sei=Yoshida en-aut-mei=Mizuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KumazawaKazumasa en-aut-sei=Kumazawa en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center kn-affil= affil-num=2 en-affil=Medical Data Labo kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Showa University Koto Toyosu Hospital kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center kn-affil= en-keyword=biomathematics kn-keyword=biomathematics en-keyword=cerebellum kn-keyword=cerebellum en-keyword=fetus kn-keyword=fetus en-keyword=trisomy 18 syndrome kn-keyword=trisomy 18 syndrome en-keyword=ultrasonography kn-keyword=ultrasonography END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=6 article-no= start-page=635 end-page=643 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MiR-338-3p Is a Biomarker in Neonatal Acute Respiratory Distress Syndrome (ARDS) and Has Roles in the Inflammatory Response of ARDS Cell Models en-subtitle= kn-subtitle= en-abstract= kn-abstract=To investigate the association between serum miR-338-3p levels and neonatal acute respiratory distress syndrome (ARDS) and its mechanism. The relative miR-338-3p expression in serum was detected by quantitative real-time RT-PCR. Interleukin-1beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) levels were detected by ELISAs. A receiver operating characteristic (ROC) curve analysis of serum miR-338-3p evaluated the diagnosis of miR-338-3p in neonatal ARDS. Pearson’s correlation analysis evaluated the correlation between serum miR-338-3p and neonatal ARDS clinical factors. Flow cytometry evaluated apoptosis, and a CCK-8 assay assessed cell viability. A luciferase assay evaluated the miR-338-3p/AKT3 relationship. The miR- 338-3p expression was decreased in neonatal ARDS patients and in lipopolysaccharide (LPS)-treated cells. The ROC curve showed the accuracy of miR-338-3p for evaluating neonatal ARDS patients. The correlation analysis demonstrated that miR-338-3p was related to PRISM-III, PaO2/FiO2, oxygenation index, IL-1β, IL-6, and TNF-α in neonatal ARDS patients. MiR-338-3p overexpression inhibited the secretion of inflammatory components, stifled cell apoptosis, and LPS-induced advanced cell viability. The double-luciferase reporter gene experiment confirmed that miR-338-3p negatively regulates AKT3 mRNA expression. Serum miR-338-3p levels were related to the diagnosis and severity of neonatal ARDS, which may be attributed to its regulatory effect on inflammatory response in ARDS. en-copyright= kn-copyright= en-aut-name=ZhangCuicui en-aut-sei=Zhang en-aut-mei=Cuicui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JiYanan en-aut-sei=Ji en-aut-mei=Yanan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangQin en-aut-sei=Wang en-aut-mei=Qin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=RuanLianying en-aut-sei=Ruan en-aut-mei=Lianying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Pediatric Intensive Care Unit, Xingtai People’s Hospital kn-affil= affil-num=2 en-affil=Pediatric Intensive Care Unit, Xingtai People’s Hospital kn-affil= affil-num=3 en-affil=Pediatric Intensive Care Unit, Xingtai People’s Hospital kn-affil= affil-num=4 en-affil=Pediatric Intensive Care Unit, Xingtai People’s Hospital kn-affil= en-keyword=miR-338-3p kn-keyword=miR-338-3p en-keyword=AKT3 kn-keyword=AKT3 en-keyword=neonatal ARDS kn-keyword=neonatal ARDS en-keyword=inflammation kn-keyword=inflammation en-keyword=diagnosis kn-keyword=diagnosis END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=5 article-no= start-page=489 end-page=502 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Insights into Mesenchymal Signatures in Glioblastoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glioblastoma (GBM) is a fatal primary malignant brain tumor in adults. Despite decades of research, the prognosis for GBM patients is still disappointing. One major reason for the intense therapeutic resistance of GBM is inter- and intra-tumor heterogeneity. GBM-intrinsic transcriptional profiling has suggested the presence of at least three subtypes of GBM: the proneural, classic, and mesenchymal subtypes. The mesenchymal subtype is the most aggressive, and patients with the mesenchymal subtype of primary and recurrent tumors tend to have a worse prognosis compared with patients with the other subtypes. Furthermore, GBM can shift from other subtypes to the mesenchymal subtype over the course of disease progression or recurrence. This phenotypic transition is driven by diverse tumor-intrinsic molecular mechanisms or microenvironmental factors. Thus, better understanding of the plastic nature of mesenchymal transition in GBM is pivotal to developing new therapeutic strategies. In this review, we provide a comprehensive overview of the current understanding of the elements involved in the mesenchymal transition of GBM and discuss future perspectives. en-copyright= kn-copyright= en-aut-name=MatsumotoYuji en-aut-sei=Matsumoto en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchikawaTomotsugu en-aut-sei=Ichikawa en-aut-mei=Tomotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=Department of Neurological Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Hamamatsu University Hospital kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=glioma kn-keyword=glioma en-keyword=glioblastoma kn-keyword=glioblastoma en-keyword=mesenchymal subtype kn-keyword=mesenchymal subtype en-keyword=mesenchymal transition kn-keyword=mesenchymal transition en-keyword=heterogeneity kn-keyword=heterogeneity END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=20 article-no= start-page=3307 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect en-subtitle= kn-subtitle= en-abstract= kn-abstract=BNCT is a non-invasive cancer therapy that allows for cancer cell death without harming adjacent cells. However, the application is limited, owing to the challenges of working with clinically approved boron (B) compounds and drug delivery systems (DDS). To address the issues, we developed self-forming nanoparticles consisting of a biodegradable polymer, namely, "AB-type Lactosome (AB-Lac)" loaded with B compounds. Three carborane isomers (o-, m-, and p-carborane) and three related alkylated derivatives, i.e., 1,2-dimethy-o-carborane (diC1-Carb), 1,2-dihexyl-o-carborane (diC6-Carb), and 1,2-didodecyl-o-carborane (diC12-Carb), were separately loaded. diC6-Carb was highly loaded with AB-Lac particles, and their stability indicated the "molecular glue" effect. The efficiency of in vitro B uptake of diC6-Carb for BNCT was confirmed at non-cytotoxic concentration in several cancer cell lines. In vivo/ex vivo biodistribution studies indicated that the AB-Lac particles were remarkably accumulated within 72 h post-injection in the tumor lesions of mice bearing syngeneic breast cancer (4T1) cells, but the maximum accumulation was reached at 12 h. In ex vivo B biodistribution, the ratios of tumor/normal tissue (T/N) and tumor/blood (T/Bl) of the diC6-Carb-loaded particles remained stably high up to 72 h. Therefore, we propose the diC6-Carb-loaded AB-Lac particles as a promising candidate medicine for BNCT. en-copyright= kn-copyright= en-aut-name=FithroniAbdul Basith en-aut-sei=Fithroni en-aut-mei=Abdul Basith kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiKazuko en-aut-sei=Kobayashi en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UjiHirotaka en-aut-sei=Uji en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshimotoManabu en-aut-sei=Ishimoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkehiMasaru en-aut-sei=Akehi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Material Chemistry, Graduate School of Engineering, Kyoto University kn-affil= affil-num=4 en-affil=Fukushima SiC Applied Engineering Inc. kn-affil= affil-num=5 en-affil=Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=boron neutron capture therapy (BNCT) kn-keyword=boron neutron capture therapy (BNCT) en-keyword=biologically self-degradable amphipathic polymer (Lactosome) kn-keyword=biologically self-degradable amphipathic polymer (Lactosome) en-keyword=hydrophobic boron cluster kn-keyword=hydrophobic boron cluster en-keyword=carborane isomers or o-carborane alkylated derivatives kn-keyword=carborane isomers or o-carborane alkylated derivatives en-keyword=molecular glue effect kn-keyword=molecular glue effect END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=1004184 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220915 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Time-series transcriptome of Brachypodium distachyon during bacterial flagellin-induced pattern-triggered immunity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plants protect themselves from microorganisms by inducing pattern-triggered immunity (PTI) via recognizing microbe-associated molecular patterns (MAMPs), conserved across many microbes. Although the MAMP perception mechanism and initial events during PTI have been well-characterized, knowledge of the transcriptomic changes in plants, especially monocots, is limited during the intermediate and terminal stages of PTI. Here, we report a time-series high-resolution RNA-sequencing (RNA-seq) analysis during PTI in the leaf disks of Brachypodium distachyon. We identified 6,039 differentially expressed genes (DEGs) in leaves sampled at 0, 0.5, 1, 3, 6, and 12 hours after treatment (hat) with the bacterial flagellin peptide flg22. The k-means clustering method classified these DEGs into 10 clusters (6 upregulated and 4 downregulated). Based on the results, we selected 10 PTI marker genes in B. distachyon. Gene ontology (GO) analysis suggested a tradeoff between defense responses and photosynthesis during PTI. The data indicated the recovery of photosynthesis started at least at 12 hat. Over-representation analysis of transcription factor genes and cis-regulatory elements in DEG promoters implied the contribution of 12 WRKY transcription factors in plant defense at the early stage of PTI induction. en-copyright= kn-copyright= en-aut-name=OgasaharaTsubasa en-aut-sei=Ogasahara en-aut-mei=Tsubasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KouzaiYusuke en-aut-sei=Kouzai en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeMegumi en-aut-sei=Watanabe en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiAkihiro en-aut-sei=Takahashi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahagiKotaro en-aut-sei=Takahagi en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimJune-Sik en-aut-sei=Kim en-aut-mei=June-Sik kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoMikihiro en-aut-sei=Yamamoto en-aut-mei=Mikihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToyodaKazuhiro en-aut-sei=Toyoda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MochidaKeiichi en-aut-sei=Mochida en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NoutoshiYoshiteru en-aut-sei=Noutoshi en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Kihara Institute for Biological Research, Yokohama City University kn-affil= affil-num=6 en-affil=Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=11 en-affil=Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=12 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Brachypodium distachyon kn-keyword=Brachypodium distachyon en-keyword=monocotyledonous plant kn-keyword=monocotyledonous plant en-keyword=microbe-associated molecular pattern kn-keyword=microbe-associated molecular pattern en-keyword=time-series transcriptome analysis kn-keyword=time-series transcriptome analysis en-keyword=reactive oxygen species kn-keyword=reactive oxygen species en-keyword=pattern-triggered immunity kn-keyword=pattern-triggered immunity END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page=994014 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cnm of Streptococcus mutans is important for cell surface structure and membrane permeability en-subtitle= kn-subtitle= en-abstract= kn-abstract=Streptococcus mutans, a Gram-positive facultative anaerobic bacterium, is a major pathogen of dental caries. The protein Cnm of S. mutans is involved in collagen binding, but its other biological functions are unknown. In this study, a Cnm-deficient isogenic mutant and a complementation strain were generated from a Cnm-positive S. mutans strain to help determine the properties of Cnm. Initially, comparison of the cell surface structure was performed by electron microscopy, which demonstrated that Cnm appears to be localized on the cell surface and associated with a protruding cell surface structure. Deep RNA sequencing of the strains revealed that the defect in Cnm caused upregulated expression of many genes related to ABC transporters and cell-surface proteins, while a few genes were downregulated. The amount of biofilm formed by the Cnm-defective strain increased compared with the parental and complemented strains, but the biofilm structure was thinner because of elevated expression of genes encoding glucan synthesis enzymes, leading to increased production of extracellular polysaccharides. Particular antibiotics, including bacitracin and chloramphenicol, had a lower minimum inhibitory concentration for the Cnm-defective strain than particular antibiotics, including bacitracin and chloramphenicol, compared with the parental and complemented strains. Our results suggest that S. mutans Cnm is located on the cell surface, gives rise to the observed protruding cell surface, and is associated with several biological properties related to membrane permeability. en-copyright= kn-copyright= en-aut-name=NakaShuhei en-aut-sei=Naka en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuokaDaiki en-aut-sei=Matsuoka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GotoKana en-aut-sei=Goto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MisakiTaro en-aut-sei=Misaki en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagasawaYasuyuki en-aut-sei=Nagasawa en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoSeigo en-aut-sei=Ito en-aut-mei=Seigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NomuraRyota en-aut-sei=Nomura en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoKazuhiko en-aut-sei=Nakano en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Matsumoto-NakanoMichiyo en-aut-sei=Matsumoto-Nakano en-aut-mei=Michiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Nephrology, Seirei Hamamatsu General Hospital kn-affil= affil-num=5 en-affil=Department of General Internal Medicine, Hyogo College of Medicine kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Japan Self-Defense Iruma Hospital kn-affil= affil-num=7 en-affil=Department of Pediatric Dentistry, Division of Oral infection and Disease Control, Osaka University Graduate School of Dentistry kn-affil= affil-num=8 en-affil=Department of Pediatric Dentistry, Division of Oral infection and Disease Control, Osaka University Graduate School of Dentistry kn-affil= affil-num=9 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Streptococcus mutans kn-keyword=Streptococcus mutans en-keyword=collagen-binding protein kn-keyword=collagen-binding protein en-keyword=membrane permeability kn-keyword=membrane permeability en-keyword=cell structure kn-keyword=cell structure en-keyword=RNA-seq kn-keyword=RNA-seq END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=10 article-no= start-page=1 end-page=8 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202285 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Wnt-β-Catenin Signaling and Sclerostin on the Phenotypes of Rat Pheochromocytoma PC12 Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pheochromocytomas and paragangliomas (PPGLs) are classified into 3 major categories with distinct driver genes: pseudohypoxia, kinase signaling, and Wnt-altered subtypes. PPGLs in the Wnt-altered subtype are sporadic and tend to be aggressive with metastasis, where somatic gene fusions affecting mastermind-like 3 (MAML3) and somatic mutations in cold shock domain containing E1 (CSDE1) cause overactivation of Wnt-β-catenin signaling. However, the relation between Wnt-β-catenin signaling and the biological behavior of PPGLs remains unexplored. In rat pheochromocytoma PC12 cells, Wnt3a treatment enhanced cell proliferation and suppressed mRNA expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis, and dopamine secretion. We identified the expression of sclerostin in PC12 cells, which is known as an osteocyte-derived negative regulator for Wnt signaling-driven bone formation. Inhibition of endogenous Wnt pathway by XAV939 or sclerostin resulted in attenuated cell proliferation and increased TH expression. Furthermore, Wnt3a pretreatment suppressed bone morphogenetic protein (BMP)-induced Smad1/5/9 phosphorylation whereas BMPs enhanced sclerostin expression in PC12 cells. In the Wnt-altered subtype, the increased Wnt-β-catenin pathway may contribute the aggressive clinical behavior with reduced catecholamine production. Furthermore, upregulated expression of sclerostin by BMPs may explain the osteolytic metastatic lesions observed in metastatic PPGLs. en-copyright= kn-copyright= en-aut-name=MorimotoEisaku en-aut-sei=Morimoto en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InagakiKenichi en-aut-sei=Inagaki en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KomatsubaraMotoshi en-aut-sei=Komatsubara en-aut-mei=Motoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TerasakaTomohiro en-aut-sei=Terasaka en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItohYoshihiko en-aut-sei=Itoh en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujisawaSatoshi en-aut-sei=Fujisawa en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SasakiErika en-aut-sei=Sasaki en-aut-mei=Erika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiyamaYuki en-aut-sei=Nishiyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HaraTakayuki en-aut-sei=Hara en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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 Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Wnt-β-catenin signaling kn-keyword=Wnt-β-catenin signaling en-keyword=sclerostin kn-keyword=sclerostin en-keyword=catecholamine kn-keyword=catecholamine en-keyword=PPGL kn-keyword=PPGL en-keyword=PC12 kn-keyword=PC12 END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=8 article-no= start-page=1253 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220819 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel Lung Growth Strategy with Biological Therapy Targeting Airway Remodeling in Childhood Bronchial Asthma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anti-inflammatory therapy, centered on inhaled steroids, suppresses airway inflammation in asthma, reduces asthma mortality and hospitalization rates, and achieves clinical remission in many pediatric patients. However, the spontaneous remission rate of childhood asthma in adulthood is not high, and airway inflammation and airway remodeling persist after remission of asthma symptoms. Childhood asthma impairs normal lung maturation, interferes with peak lung function in adolescence, reduces lung function in adulthood, and increases the risk of developing chronic obstructive pulmonary disease (COPD). Early suppression of airway inflammation in childhood and prevention of asthma exacerbations may improve lung maturation, leading to good lung function and prevention of adult COPD. Biological drugs that target T-helper 2 (Th2) cytokines are used in patients with severe pediatric asthma to reduce exacerbations and airway inflammation and improve respiratory function. They may also suppress airway remodeling in childhood and prevent respiratory deterioration in adulthood, reducing the risk of COPD and improving long-term prognosis. No studies have demonstrated a suppressive effect on airway remodeling in childhood severe asthma, and further clinical trials using airway imaging analysis are needed to ascertain the inhibitory effect of biological drugs on airway remodeling in severe childhood asthma. In this review, we describe the natural prognosis of lung function in childhood asthma and the risk of developing adult COPD, the pathophysiology of allergic airway inflammation and airway remodeling via Th2 cytokines, and the inhibitory effect of biological drugs on airway remodeling in childhood asthma. en-copyright= kn-copyright= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Pediatric Acute Diseases, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Okayama University School of Medicine kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=bronchial asthma kn-keyword=bronchial asthma en-keyword=chronic obstructive pulmonary disease kn-keyword=chronic obstructive pulmonary disease en-keyword=lung function trajectory kn-keyword=lung function trajectory en-keyword=type 2 inflammation kn-keyword=type 2 inflammation en-keyword=airway remodeling kn-keyword=airway remodeling en-keyword=omalizumab kn-keyword=omalizumab en-keyword=mepolizumab kn-keyword=mepolizumab en-keyword=benralizumab kn-keyword=benralizumab en-keyword=dupilumab kn-keyword=dupilumab END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=13 article-no= start-page=5207 end-page=5220 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220808 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nitroxoline suppresses metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bladder cancer is one of the most common and deadly cancer worldwide. Current chemotherapy has shown limited efficacy in improving outcomes for patients. Nitroxoline, an old and widely used oral antibiotic, which was known to treat for urinary tract infection for decades. Recent studies suggested that nitroxoline suppressed the tumor progression and metastasis, especially in bladder cancer. However, the underlying mechanism for anti-tumor activity of nitroxoline remains unclear. Methods: CircRNA microarray was used to explore the nitroxoline-mediated circRNA expression profile of bladder cancer lines. Transwell and wound-healing assay were applied to evaluate the capacity of metastasis. ChIP assay was chosen to prove the binding of promotor and transcription factor. RNA-pulldown assay was performed to explore the sponge of circRNA and microRNA. Results: We first identified the circNDRG1 (has_circ_0085656) as a novel candidate circRNA. Transwell and wound-healing assay demonstrated that circNDRG1 inhibited the metastasis of bladder cancer. ChIP assay showed that circNDRG1 was regulated by the transcription factor EGR1 by binding the promotor of host gene NDRG1. RNA-pulldown assay proved that circNDRG1 sponged miR-520h leading to the overexpression of smad7, which was a negative regulatory protein of EMT. Conclusions: Our research revealed that nitroxoline may suppress metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway. en-copyright= kn-copyright= en-aut-name=RenLiangliang en-aut-sei=Ren en-aut-mei=Liangliang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JiangMinxiao en-aut-sei=Jiang en-aut-mei=Minxiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=XueDingwei en-aut-sei=Xue en-aut-mei=Dingwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangHuan en-aut-sei=Wang en-aut-mei=Huan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LuZeyi en-aut-sei=Lu en-aut-mei=Zeyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DingLifeng en-aut-sei=Ding en-aut-mei=Lifeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=XieHaiyun en-aut-sei=Xie en-aut-mei=Haiyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WangRuyue en-aut-sei=Wang en-aut-mei=Ruyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LuoWenqin en-aut-sei=Luo en-aut-mei=Wenqin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=XuLi en-aut-sei=Xu en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WangMingchao en-aut-sei=Wang en-aut-mei=Mingchao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YuShicheng en-aut-sei=Yu en-aut-mei=Shicheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ChengSheng en-aut-sei=Cheng en-aut-mei=Sheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=XiaLiqun en-aut-sei=Xia en-aut-mei=Liqun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YuHaifeng en-aut-sei=Yu en-aut-mei=Haifeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HuangPeng en-aut-sei=Huang en-aut-mei=Peng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=XuNaijin en-aut-sei=Xu en-aut-mei=Naijin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=LiGonghui en-aut-sei=Li en-aut-mei=Gonghui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=2 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=3 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=7 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=8 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=9 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=14 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=15 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=16 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= affil-num=18 en-affil=Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine kn-affil= en-keyword=Bladder cancer kn-keyword=Bladder cancer en-keyword=nitroxoline kn-keyword=nitroxoline en-keyword=metastasis circNDRG1 kn-keyword=metastasis circNDRG1 en-keyword=microRNA kn-keyword=microRNA END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=1722 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220804 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Transfectable Fusagravirus from a Japanese Strain of Cryphonectria carpinicola with Spherical Particles en-subtitle= kn-subtitle= en-abstract= kn-abstract=A novel dsRNA virus (Cryphonectria carpinicola fusagravirus 1, CcFGV1), isolated from a Japanese strain (JS13) of Cryphonectria carpinicola, was thoroughly characterized. The biological comparison of a set of isogenic CcFGV1-infected and -free (JS13VF) strains indicated asymptomatic infection by CcFGV1. The sequence analysis showed that the virus has a two open reading frame (ORF) genome of 9.6 kbp with the RNA-directed RNA polymerase domain encoded by ORF2. The N-terminal sequencing and peptide mass fingerprinting showed an N-terminally processed or degraded product (150 kDa) of the 5'-proximal ORF1-encoded protein (1462 amino acids) to make up the CcFGV1 spherical particles of similar to 40 nm in diameter. Interestingly, a portion of CcFGV1 dsRNA co-fractionated with a host protein of 70 kDa. The purified CcFGV1 particles were used to transfect protoplasts of JS13VF as well as the standard strain of an experimental model filamentous fungal host Cryphonectria parasitica. CcFGV1 was confirmed to be associated with asymptomatic infection of both fungi. RNA silencing was shown to target the virus in C. parasitica, resulting in reduced CcFGV1 accumulation by comparing the CcFGV1 content between RNA silencing-competent and -deficient strains. These results indicate the transfectability of spherical particles of a fusagravirus associated with asymptomatic infection. en-copyright= kn-copyright= en-aut-name=DasSubha en-aut-sei=Das en-aut-mei=Subha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HisanoSakae en-aut-sei=Hisano en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Eusebio-CopeAna en-aut-sei=Eusebio-Cope en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Cryphonectria carpinicola kn-keyword=Cryphonectria carpinicola en-keyword=Cryphonectria parasitica kn-keyword=Cryphonectria parasitica en-keyword=fusagravirus kn-keyword=fusagravirus en-keyword=fungal virus kn-keyword=fungal virus en-keyword=dsRNA kn-keyword=dsRNA en-keyword=spherical virion kn-keyword=spherical virion en-keyword=transfection kn-keyword=transfection END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=891925 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220802 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Responses of regulatory and effector T-cells to low-dose interleukin-2 differ depending on the immune environment after allogeneic stem cell transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=CD4(+)Foxp3(+) regulatory T cells (Tregs) play a central role in the maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT). Tregs promptly respond to low concentrations of IL-2 through the constitutive expression of high-affinity IL-2 receptors. It has been reported that low-dose IL-2 therapy increased circulating Tregs and improved clinical symptoms of chronic GVHD. Clinical studies of IL-2 therapy so far have mainly targeted patients in the chronic phase of transplantation when acute immune responses has subsided. However, the biological and clinical effects of exogenous IL-2 in an acute immune environment have not been well investigated. In the current study, we investigated the impact of exogenous IL-2 therapy on the post-transplant homeostasis of T cell subsets which influence the balance between GVHD and GVL in the acute phase, by setting the various immune environments early after HSCT in murine model. We initially found that 5,000 IU of IL-2 was enough to induce the active proliferation of Treg without influencing other conventional T cells (Tcons) when administered to normal mice. However, activated Tcons showed the response to the same dose of IL-2 in recipients after allogeneic HSCT. In a mild inflammatory environment within a threshold, exogenous IL-2 could effectively modulate Treg homeostasis with just limited influence to activated T cells, which resulted in an efficient GVHD suppression. In contrast, in a severely inflammatory environment, exogenous IL-2 enhanced activated T cells rather than Tregs, which resulted in the exacerbation of GVHD. Of interest, in an immune-tolerant state after transplant, exogenous IL-2 triggered effector T-cells to exert an anti-tumor effect with maintaining GVHD suppression. These data suggested that the responses of Tregs and effector T cells to exogenous IL-2 differ depending on the immune environment in the host, and the mutual balance of the response to IL-2 between T-cell subsets modulates GVHD and GVL after HSCT. Our findings may provide useful information in the optimization of IL-2 therapy, which may be personalized for each patient having different immune status. en-copyright= kn-copyright= en-aut-name=MeguriYusuke en-aut-sei=Meguri en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanoTakeru en-aut-sei=Asano en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshiokaTakanori en-aut-sei=Yoshioka en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwamotoMiki en-aut-sei=Iwamoto en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkegawaShuntaro en-aut-sei=Ikegawa en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiuraHiroyuki en-aut-sei=Sugiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KishiYuriko en-aut-sei=Kishi en-aut-mei=Yuriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraMakoto en-aut-sei=Nakamura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SandoYasuhisa en-aut-sei=Sando en-aut-mei=Yasuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SumiiYuichi en-aut-sei=Sumii en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=regulatory T cell kn-keyword=regulatory T cell en-keyword=low-dose interleukin-2 therapy kn-keyword=low-dose interleukin-2 therapy en-keyword=graft-versus-host disease kn-keyword=graft-versus-host disease en-keyword=graft-versus-leukemia effect kn-keyword=graft-versus-leukemia effect en-keyword=transplantation tolerance kn-keyword=transplantation tolerance END start-ver=1.4 cd-journal=joma no-vol=2022 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220724 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Drug repositioning of tranilast to sensitize a cancer therapy by targeting cancer-associated fibroblast en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment that mediate resistance of cancer cells to anticancer drugs. Tranilast is an antiallergic drug that suppresses the release of cytokines from various inflammatory cells. In this study, we investigated the inhibitory effect of tranilast on the interactions between non-small cell lung cancer (NSCLC) cells and the CAFs in the tumor microenvironment. Three EGFR-mutant NSCLC cell lines, two KRAS-mutant cell lines, and three CAFs derived from NSCLC patients were used. To mimic the tumor microenvironment, the NSCLC cells were cocultured with the CAFs in vitro, and the molecular profiles and sensitivity to molecular targeted therapy were assessed. Crosstalk between NSCLC cells and CAFs induced multiple biological effects on the NSCLC cells both in vivo and in vitro, including activation of the STAT3 signaling pathway, promotion of xenograft tumor growth, induction of epithelial-mesenchymal transition (EMT), and acquisition of resistance to molecular-targeted therapy, including EGFR-mutant NSCLC cells to osimertinib and of KRAS-mutant NSCLC cells to selumetinib. Treatment with tranilast led to inhibition of IL-6 secretion from the CAFs, which, in turn, resulted in inhibition of CAF-induced phospho-STAT3 upregulation. Tranilast also inhibited CAF-induced EMT in the NSCLC cells. Finally, combined administration of tranilast with molecular-targeted therapy reversed the CAF-mediated resistance of the NSCLC cells to the molecular-targeted drugs, both in vitro and in vivo. Our results showed that combined administration of tranilast with molecular-targeted therapy is a possible new treatment strategy to overcome drug resistance caused by cancer-CAF interaction. en-copyright= kn-copyright= en-aut-name=OchiKosuke en-aut-sei=Ochi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ThuYin Min en-aut-sei=Thu en-aut-mei=Yin Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakatsuFumiaki en-aut-sei=Takatsu en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsudakaShimpei en-aut-sei=Tsudaka en-aut-mei=Shimpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhuYidan en-aut-sei=Zhu en-aut-mei=Yidan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakataKentaro en-aut-sei=Nakata en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakedaTatsuaki en-aut-sei=Takeda en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkamotoYoshiharu en-aut-sei=Okamoto en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Departments of Pharmacy, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Veterinary Clinical Medicine, Joint School of Veterinary Medicine, Tottori University kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cancer-associated fibroblast kn-keyword=cancer-associated fibroblast en-keyword=drug resistance kn-keyword=drug resistance en-keyword=tranilast kn-keyword=tranilast END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=15 article-no= start-page=8592 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220802 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fibroblast Growth Factors and Cellular Communication Network Factors: Intimate Interplay by the Founding Members in Cartilage en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fibroblast growth factors (FGFs) constitute a large family of signaling molecules that act in an autocrine/paracrine, endocrine, or intracrine manner, whereas the cellular communication network factors (CCN) family is composed of six members that manipulate extracellular signaling networks. FGFs and CCNs are structurally and functionally distinct, except for the common characteristics as matricellular proteins. Both play significant roles in the development of a variety of tissues and organs, including the skeletal system. In vertebrates, most of the skeletal parts are formed and grow through a process designated endochondral ossification, in which chondrocytes play the central role. The growth plate cartilage is the place where endochondral ossification occurs, and articular cartilage is left to support the locomotive function of joints. Several FGFs, including FGF-2, one of the founding members of this family, and all of the CCNs represented by CCN2, which is required for proper skeletal development, can be found therein. Research over a decade has revealed direct binding of CCN2 to FGFs and FGF receptors (FGFRs), which occasionally affect the biological outcome via FGF signaling. Moreover, a recent study uncovered an integrated regulation of FGF and CCN genes by FGF signaling. In this review, after a brief introduction of these two families, molecular and genetic interactions between CCN and FGF family members in cartilage, and their biological effects, are summarized. The molecular interplay represents the mutual involvement of the other in their molecular functions, leading to collaboration between CCN2 and FGFs during skeletal development. en-copyright= kn-copyright= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AoyamaEriko en-aut-sei=Aoyama en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=NishidaTakashi en-aut-sei=Nishida en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Biochemistry and Molecular Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Biochemistry and Molecular Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=fibroblast growth factor kn-keyword=fibroblast growth factor en-keyword=cellular communication network factor kn-keyword=cellular communication network factor en-keyword=cartilage kn-keyword=cartilage en-keyword=skeletal development kn-keyword=skeletal development en-keyword=CCN2 kn-keyword=CCN2 END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=7 article-no= start-page=104524 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220715 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lattice-patterned collagen fibers and their dynamics in axolotl skin regeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=The morphology of collagen-producing cells and the structure of produced collagen in the dermis have not been well-described. This lack of insights has been a serious obstacle in the evaluation of skin regeneration. We succeeded in visualizing collagen-producing cells and produced collagen using the axolotl skin, which is highly transparent. The visualized dermal collagen had a lattice-like structure. The collagen-producing fibroblasts consistently possessed the lattice-patterned filopodia along with the lattice-patterned collagen network. The dynamics of this lattice-like structure were also verified in the skin regeneration process of axolotls, and it was found that the correct lattice-like structure was not reorganized after simple skin wounding but was reorganized in the presence of nerves. These findings are not only fundamental insights in dermatology but also valuable insights into the mechanism of skin regeneration. en-copyright= kn-copyright= en-aut-name=KashimotoRena en-aut-sei=Kashimoto en-aut-mei=Rena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FurukawaSaya en-aut-sei=Furukawa en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoSakiya en-aut-sei=Yamamoto en-aut-mei=Sakiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KameiYasuhiro en-aut-sei=Kamei en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoJoe en-aut-sei=Sakamoto en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NonakaShigenori en-aut-sei=Nonaka en-aut-mei=Shigenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeTomonobu M. en-aut-sei=Watanabe en-aut-mei=Tomonobu M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakamotoTatsuya en-aut-sei=Sakamoto en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SakamotoHirotaka en-aut-sei=Sakamoto en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Biological Sciences, Faculty of Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Biological Sciences, Faculty of Science, Okayama University kn-affil= affil-num=4 en-affil=National Institute for Basic Biology (NIBB), National Institutes for Natural Sciences kn-affil= affil-num=5 en-affil=National Institute for Basic Biology (NIBB), National Institutes for Natural Sciences kn-affil= affil-num=6 en-affil=National Institute for Basic Biology (NIBB), National Institutes for Natural Sciences kn-affil= affil-num=7 en-affil=Laboratory for Comprehensive Bioimaging, RIKEN Center for Biosystems Dynamics Research (BDR) kn-affil= affil-num=8 en-affil=Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Research Core for Interdisciplinary Sciences (RCIS), Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=921636 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Periplasmic Lanthanide Mediator, Lanmodulin, in Methylobacterium aquaticum Strain 22A en-subtitle= kn-subtitle= en-abstract= kn-abstract=Methylobacterium and Methylorubrum species oxidize methanol via pyrroloquinoline quinone-methanol dehydrogenases (MDHs). MDHs can be classified into two major groups, Ca2+-dependent MDH (MxaF) and lanthanide (Ln(3+))-dependent MDH (XoxF), whose expression is regulated by the availability of Ln(3+). A set of a siderophore, TonB-dependent receptor, and an ABC transporter that resembles the machinery for iron uptake is involved in the solubilization and transport of Ln(3+). The transport of Ln(3+) into the cytosol enhances XoxF expression. A unique protein named lanmodulin from Methylorubrum extorquens strain AM1 was identified as a specific Ln(3+)-binding protein, and its biological function was implicated to be an Ln(3+) shuttle in the periplasm. In contrast, it remains unclear how Ln(3+) levels in the cells are maintained, because Ln(3+) is potentially deleterious to cellular systems due to its strong affinity to phosphate ions. In this study, we investigated the function of a lanmodulin homolog in Methylobacterium aquaticum strain 22A. The expression of a gene encoding lanmodulin (lanM) was induced in response to the presence of La3+. A recombinant LanM underwent conformational change upon La3+ binding. Phenotypic analyses on lanM deletion mutant and overexpressing strains showed that LanM is not necessary for the wild-type and XoxF-dependent mutant's methylotrophic growth. We found that lanM expression was regulated by MxcQE (a two-component regulator for MxaF) and TonB_Ln (a TonB-dependent receptor for Ln(3+)). The expression level of mxcQE was altered to be negatively dependent on Ln(3+) concentration in increment lanM, whereas it was constant in the wild type. Furthermore, when exposed to La3+, increment lanM showed an aggregating phenotype, cell membrane impairment, La deposition in the periplasm evidenced by electron microscopy, differential expression of proteins involved in membrane integrity and phosphate starvation, and possibly lower La content in the membrane vesicle (MV) fractions. Taken together, we concluded that lanmodulin is involved in the complex regulation mechanism of MDHs and homeostasis of cellular Ln levels by facilitating transport and MV-mediated excretion. en-copyright= kn-copyright= en-aut-name=FujitaniYoshiko en-aut-sei=Fujitani en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShibataTakeshi en-aut-sei=Shibata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaniAkio en-aut-sei=Tani en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=K.K. AB SCIEX kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=lanmodulin kn-keyword=lanmodulin en-keyword=lanthanide kn-keyword=lanthanide en-keyword=methanol dehydrogenase kn-keyword=methanol dehydrogenase en-keyword=Methylobacterium species kn-keyword=Methylobacterium species en-keyword=membrane vesicles kn-keyword=membrane vesicles END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220705 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tumor size before image-guided brachytherapy is an important factor of local control after radiotherapy for cervical squamous cell carcinoma: analysis in cases using central shielding en-subtitle= kn-subtitle= en-abstract= kn-abstract=We analyzed the local control (LC) of cervical squamous cell carcinoma treated by computed tomography (CT)-based image-guided brachytherapy (IGBT) using central shielding (CS). We also examined the value of tumor diameter before brachytherapy (BT) as a factor of LC. In total, 97 patients were analyzed between April 2016 and March 2020. Whole-pelvic (WP) radiotherapy (RT) with CS was performed, and the total pelvic sidewall dose was 50 or 50.4 Gy; IGBT was delivered in 3-4 fractions. The total dose was calculated as the biologically equivalent dose in 2 Gy fractions, and distribution was modified manually by graphical optimization. The median follow-up period was 31.8 months (6.3-63.2 months). The 1- and 2-year LC rates were 89% and 87%, respectively. The hazard ratio was 10.11 (95% confidence interval: 1.48-68.99) for local recurrence in those with a horizontal tumor diameter >= 4 cm compared to those with < 4 cm before BT. In CT-based IGBT for squamous cell carcinoma, favorable LC can be obtained in patients with a tumor diameter < 4 cm before BT. However, if the tumor diameter is >= 4 cm, different treatment strategies such as employing interstitial-BT for dose escalation may be necessary. en-copyright= kn-copyright= en-aut-name=YoshioKotaro en-aut-sei=Yoshio en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IharaHiroki en-aut-sei=Ihara en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OgataTakeshi en-aut-sei=Ogata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiyamaSoichi en-aut-sei=Sugiyama en-aut-mei=Soichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagaoShoji en-aut-sei=Nagao en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Proton Beam Therapy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Radiology, Tsuyama Central Hospital kn-affil= affil-num=6 en-affil=Department of Proton Beam Therapy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Obstetrics and Gynecology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cervical cancer kn-keyword=cervical cancer en-keyword=tumor size kn-keyword=tumor size en-keyword=squamous cell carcinoma kn-keyword=squamous cell carcinoma en-keyword=image-guided brachytherapy (IGBT) kn-keyword=image-guided brachytherapy (IGBT) en-keyword=central shielding (CS) kn-keyword=central shielding (CS) END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=3 article-no= start-page=333 end-page=338 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful Treatment of Atypical Femoral Fracture with Bowed Femur Using Contralateral Intramedullary Nail Combined with Early Daily Teriparatide en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a case of atypical femoral fracture achieving early fracture union with combination therapy comprising contralateral nail and immediate teriparatide injection. Fracture union of atypical fractures is often delayed due to bowing deformity and bone metabolic disorders. Combination treatment that takes both problems into consideration represents a useful treatment option for atypical femoral fracture. en-copyright= kn-copyright= en-aut-name=AkagawaManabu en-aut-sei=Akagawa en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyakoshiNaohisa en-aut-sei=Miyakoshi en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchieHiroyuki en-aut-sei=Tsuchie en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KasukawaYuji en-aut-sei=Kasukawa en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaragiTakashi en-aut-sei=Kawaragi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagahataItsuki en-aut-sei=Nagahata en-aut-mei=Itsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzukiMasazumi en-aut-sei=Suzuki en-aut-mei=Masazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshikawaTakayuki en-aut-sei=Yoshikawa en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AbeToshiki en-aut-sei=Abe en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShimadaYoichi en-aut-sei=Shimada en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Omagari Kosei Medical Center kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Omagari Kosei Medical Center kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Omagari Kosei Medical Center kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Omagari Kosei Medical Center kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Omagari Kosei Medical Center kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Omagari Kosei Medical Center kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Akita University Graduate School of Medicine kn-affil= en-keyword=atypical femoral fracture kn-keyword=atypical femoral fracture en-keyword=bowing deformity kn-keyword=bowing deformity en-keyword=intramedullary nail kn-keyword=intramedullary nail en-keyword=teriparatide kn-keyword=teriparatide en-keyword=cephalomedullary screw kn-keyword=cephalomedullary screw END start-ver=1.4 cd-journal=joma no-vol=1866 cd-vols= no-issue=8 article-no= start-page=130171 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Metformin-ROS-Nrf2 connection in the host defense mechanism against oxidative stress, apoptosis, cancers, and ageing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reactive oxygen species (ROS) acts as a second messenger to trigger biological responses in low concentrations, while it is implicated to be toxic to biomolecules in high concentrations. Mild inhibition of respiratory chain Complex I by metformin at physiologically relevant concentrations stimulates production of low-level mitochondrial ROS. The ROS seems to induce anti-oxidative stress response via activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase (GPx), which results in not only elimination of ROS but also activation of cellular responses including resistance to apoptosis, metabolic changes, cell proliferation, senescence prevention, lifespan extension, and immune T cell activation against cancers, regardless of its effect controlling blood glucose level and T2DM. Although metformin's effect against T2DM, cancers, and ageing, are believed mostly attributed to the activation of AMP-activated protein kinase (AMPK), the cellular responses involving metformin-ROS-Nrf2 axis might be another natural asset to improve healthspan and lifespan. en-copyright= kn-copyright= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishidaMikako en-aut-sei=Nishida en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Mitochondrial ROS kn-keyword=Mitochondrial ROS en-keyword=Oxidative stress kn-keyword=Oxidative stress en-keyword=Apoptosis kn-keyword=Apoptosis en-keyword=Ageing kn-keyword=Ageing en-keyword=Nrf2 kn-keyword=Nrf2 END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=37 article-no= start-page=e202201253 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220523 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Design and Synthesis of Glycosylated Cholera Toxin B Subunit as a Tracer of Glycoprotein Trafficking in Organelles of Living Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glycosylation of proteins is known to be essential for changing biological activity and stability of glycoproteins on the cell surfaces and in body fluids. Delivering of homogeneous glycoproteins into the endoplasmic reticulum (ER) and the Golgi apparatus would enable us to investigate the function of asparagine-linked (N-) glycans in the organelles. In this work, we designed and synthesized an intentionally glycosylated cholera toxin B-subunit (CTB) to be transported to the organelles of mammalian cells. The heptasaccharide, the intermediate structure of various complex-type N-glycans, was introduced to the CTB. The synthesized monomeric glycosyl-CTB successfully entered mammalian cells and was transported to the Golgi and the ER, suggesting the potential use of synthetic CTB to deliver and investigate the functions of homogeneous N-glycans in specific organelles of living cells. en-copyright= kn-copyright= en-aut-name=MakiYuta en-aut-sei=Maki en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawataKazuki en-aut-sei=Kawata en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiuYanbo en-aut-sei=Liu en-aut-mei=Yanbo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GooKang‐Ying en-aut-sei=Goo en-aut-mei=Kang‐Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkamotoRyo en-aut-sei=Okamoto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KajiharaYasuhiro en-aut-sei=Kajihara en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=2 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=3 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=4 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=6 en-affil=Department of Chemistry, Graduate School of Science, Osaka University kn-affil= affil-num=7 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=glycoprotein kn-keyword=glycoprotein en-keyword=N-glycan kn-keyword=N-glycan en-keyword=cholera toxin kn-keyword=cholera toxin en-keyword=native chemical ligation kn-keyword=native chemical ligation en-keyword=live imaging kn-keyword=live imaging END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=3 article-no= start-page=235 end-page=245 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of Transmembrane Protein 97 (TMEM97) in Adipose Tissue and Skeletal Muscle en-subtitle= kn-subtitle= en-abstract= kn-abstract=The combination of sarcopenia and obesity (sarcopenic obesity) is associated with the development of metabolic syndrome and cardiovascular events. The molecular pathways that develop sarcopenic obesity have studied intensively. Transmembrane protein 97 (TMEM97) is 176 amino acids conserved integral membrane protein with four transmembrane domains that is expressed in several types of cancer. Its physiological significance in adipose tissue and skeletal muscle has been unclear. We studied TMEM97-transgenic mice and mice lacking TMEM97, and our findings indicate that TMEM97 expression is regulated in adipose tissue and skeletal muscle from obesity. TMEM97 represses adipogenesis and promotes myogenesis in vitro. Fat-specific TMEM97 transgenic mice showed systemic insulin resistance. Mice overexpressing TMEM97 in skeletal muscle exhibited systemic insulin resistance. Mice lacking TMEM97 were protected against diet-induced obesity and insulin resistance. These phenotypes are associated with the effects of TMEM97 on inflammation genes in adipose tissue and skeletal muscle. Our findings indicates that there is a link between TMEM97 and chronic inflammation in obesity. en-copyright= kn-copyright= en-aut-name=TentaMasafumi en-aut-sei=Tenta en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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= en-keyword=adipose tissue kn-keyword=adipose tissue en-keyword=skeletal muscle kn-keyword=skeletal muscle en-keyword=obesity kn-keyword=obesity END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=884509 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Lipid-Binding Defective Dynamin 2 Mutant in Charcot-Marie-Tooth Disease Impairs Proper Actin Bundling and Actin Organization in Glomerular Podocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dynamin is an endocytic protein that functions in vesicle formation by scission of invaginated membranes. Dynamin maintains the structure of foot processes in glomerular podocytes by directly and indirectly interacting with actin filaments. However, molecular mechanisms underlying dynamin-mediated actin regulation are largely unknown. Here, biochemical and cell biological experiments were conducted to uncover how dynamin modulates interactions between membranes and actin in human podocytes. Actin-bundling, membrane tubulating, and GTPase activities of dynamin were examined in vitro using recombinant dynamin 2-wild-type (WT) or dynamin 2-K562E, which is a mutant found in Charcot-Marie-Tooth patients. Dynamin 2-WT and dynamin 2-K562E led to the formation of prominent actin bundles with constant diameters. Whereas liposomes incubated with dynamin 2-WT resulted in tubule formation, dynamin 2-K562E reduced tubulation. Actin filaments and liposomes stimulated dynamin 2-WT GTPase activity by 6- and 20-fold, respectively. Actin-filaments, but not liposomes, stimulated dynamin 2-K562E GTPase activity by 4-fold. Self-assembly-dependent GTPase activity of dynamin 2-K562E was reduced to one-third compared to that of dynamin 2-WT. Incubation of liposomes and actin with dynamin 2-WT led to the formation of thick actin bundles, which often bound to liposomes. The interaction between lipid membranes and actin bundles by dynamin 2-K562E was lower than that by dynamin 2-WT. Dynamin 2-WT partially colocalized with stress fibers and actin bundles based on double immunofluorescence of human podocytes. Dynamin 2-K562E expression resulted in decreased stress fiber density and the formation of aberrant actin clusters. Dynamin 2-K562E colocalized with alpha-actinin-4 in aberrant actin clusters. Reformation of stress fibers after cytochalasin D-induced actin depolymerization and washout was less effective in dynamin 2-K562E-expressing cells than that in dynamin 2-WT. Bis-T-23, a dynamin self-assembly enhancer, was unable to rescue the decreased focal adhesion numbers and reduced stress fiber density induced by dynamin 2-K562E expression. These results suggest that the low affinity of the K562E mutant for lipid membranes, and atypical self-assembling properties, lead to actin disorganization in HPCs. Moreover, lipid-binding and self-assembly of dynamin 2 along actin filaments are required for podocyte morphology and functions. Finally, dynamin 2-mediated interactions between actin and membranes are critical for actin bundle formation in HPCs. en-copyright= kn-copyright= en-aut-name=HamasakiEriko en-aut-sei=Hamasaki en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WakitaNatsuki en-aut-sei=Wakita en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuokaHiroki en-aut-sei=Yasuoka en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NagaokaHikaru en-aut-sei=Nagaoka en-aut-mei=Hikaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaMasayuki en-aut-sei=Morita en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakashimaEizo en-aut-sei=Takashima en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UchihashiTakayuki en-aut-sei=Uchihashi en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakedaTetsuya en-aut-sei=Takeda en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AbeTadashi en-aut-sei=Abe en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LeeJi-Won en-aut-sei=Lee en-aut-mei=Ji-Won kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IimuraTadahiro en-aut-sei=Iimura en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SaleemMoin A. en-aut-sei=Saleem en-aut-mei=Moin A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OgoNaohisa en-aut-sei=Ogo en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AsaiAkira en-aut-sei=Asai en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NaritaAkihiro en-aut-sei=Narita en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TakeiKohji en-aut-sei=Takei en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamadaHiroshi en-aut-sei=Yamada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Division of Malaria Research, Proteo-Science Center, Ehime University kn-affil= affil-num=5 en-affil=Division of Malaria Research, Proteo-Science Center, Ehime University kn-affil= affil-num=6 en-affil=Division of Malaria Research, Proteo-Science Center, Ehime University kn-affil= affil-num=7 en-affil=Department of Physics, Nagoya University kn-affil= affil-num=8 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pharmacology, Faculty and Graduate School of Dental Medicine, Hokkaido University kn-affil= affil-num=11 en-affil=Department of Pharmacology, Faculty and Graduate School of Dental Medicine, Hokkaido University kn-affil= affil-num=12 en-affil=Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol kn-affil= affil-num=13 en-affil=Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka kn-affil= affil-num=14 en-affil=Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka kn-affil= affil-num=15 en-affil=Graduate School of Science, Nagoya University kn-affil= affil-num=16 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=dynamin kn-keyword=dynamin en-keyword=podocyte kn-keyword=podocyte en-keyword=actin kn-keyword=actin en-keyword=bundle kn-keyword=bundle en-keyword=GTPase kn-keyword=GTPase en-keyword=CMT kn-keyword=CMT END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue= article-no= start-page=249 end-page=261 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220616 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Modulation of p53 expression in cancer-associated fibroblasts prevents peritoneal metastasis of cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are associated with the establishment and progression of peritoneal metastasis. This study investigated the efficacy of replicative oncolytic adenovirus-mediated p53 gene therapy (OBP-702) against CAFs and peritoneal metastasis of gastric cancer (GC). Higher CAF expression in the primary tumor was associated with poor prognosis of GC, and higher CAF expression was also observed with peritoneal metastasis in immunohistochemical analysis of clinical samples. And, we found transcriptional alteration of p53 in CAFs relative to normal gastric fibroblasts (NGFs). CAFs increased the secretion of cancer-promoting cytokines, including interleukin-6, and gained resistance to chemotherapy relative to NGFs. OBP-702 showed cytotoxicity to both GC cells and CAFs but not to NGFs. Overexpression of wild-type p53 by OBP-702 infection caused apoptosis and autophagy of CAFs and decreased the secretion of cancer-promoting cytokines by CAFs. Combination therapy using intraperitoneal administration of OBP-702 and paclitaxel synergistically inhibited the tumor growth of peritoneal metastases and decreased CAFs in peritoneal metastases. OBP-702, a replicative oncolytic adenovirus-mediated p53 gene therapy, offers a promising biological therapeutic strategy for peritoneal metastasis, modulating CAFs in addition to achieving tumor lysis. en-copyright= kn-copyright= en-aut-name=OgawaToshihiro en-aut-sei=Ogawa en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TabuchiMotoyasu en-aut-sei=Tabuchi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuiEma en-aut-sei=Mitsui en-aut-mei=Ema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UneYuta en-aut-sei=Une en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Oncolys BioPharma kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=149 cd-vols= no-issue=8 article-no= start-page=dev199916 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211109 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Toll signalling promotes blastema cell proliferation during cricket leg regeneration via insect macrophages en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hemimetabolous insects, such as the two-spotted cricket Gryllus bimaculatus, can recover lost tissues, in contrast to the limited regenerative abilities of human tissues. Following cricket leg amputation, the wound surface is covered by the wound epidermis, and plasmatocytes, which are insect macrophages, accumulate in the wound region. Here, we studied the function of Toll-related molecules identified by comparative RNA sequencing during leg regeneration. Of the 11 Toll genes in the Gryllus genome, expression of Toll2-1, Toll2-2 and Toll2-5 was upregulated during regeneration. RNA interference (RNAi) of Toll, Toll2-1, Toll2-2, Toll2-3 or Toll2-4 produced regeneration defects in more than 50% of crickets. RNAi of Toll2-2 led to a decrease in the ratio of S- and M-phase cells, reduced expression of JAK/STAT signalling genes, and reduced accumulation of plasmatocytes in the blastema. Depletion of plasmatocytes in crickets using clodronate also produced regeneration defects, as well as fewer proliferating cells in the regenerating legs. Plasmatocyte depletion also downregulated the expression of Toll and JAK/STAT signalling genes in the regenerating legs. These results suggest that Spz-Toll-related signalling in plasmatocytes promotes leg regeneration through blastema cell proliferation by regulating the Upd-JAK/STAT signalling pathway. en-copyright= kn-copyright= en-aut-name=BandoTetsuya en-aut-sei=Bando en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkumuraMisa en-aut-sei=Okumura en-aut-mei=Misa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BandoYuki en-aut-sei=Bando en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HagiwaraMarou en-aut-sei=Hagiwara en-aut-mei=Marou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamadaYoshimasa en-aut-sei=Hamada en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshimaruYoshiyasu en-aut-sei=Ishimaru en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MitoTaro en-aut-sei=Mito en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawaguchiEri en-aut-sei=Kawaguchi en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InoueTakeshi en-aut-sei=Inoue en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AgataKiyokazu en-aut-sei=Agata en-aut-mei=Kiyokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NojiSumihare en-aut-sei=Noji en-aut-mei=Sumihare kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Faculty of Medicine, Okayama University Medical School kn-affil= affil-num=4 en-affil=Faculty of Medicine, Okayama University Medical School kn-affil= affil-num=5 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University kn-affil= affil-num=7 en-affil=Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University kn-affil= affil-num=8 en-affil=Division of Biological Science, Graduate School of Science, Kyoto University kn-affil= affil-num=9 en-affil=Division of Biological Science, Graduate School of Science, Kyoto University kn-affil= affil-num=10 en-affil=Division of Biological Science, Graduate School of Science, Kyoto University kn-affil= affil-num=11 en-affil=Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University kn-affil= affil-num=12 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Regeneration kn-keyword=Regeneration en-keyword=Toll-related signalling kn-keyword=Toll-related signalling en-keyword=JAK/STAT signalling kn-keyword=JAK/STAT signalling en-keyword=Macrophages kn-keyword=Macrophages en-keyword=Blastema kn-keyword=Blastema en-keyword=Gryllus bimaculatus kn-keyword=Gryllus bimaculatus END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=9 article-no= start-page=eabk0331 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202234 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vasopressin-oxytocin?type signaling is ancient and has a conserved water homeostasis role in euryhaline marine planarians en-subtitle= kn-subtitle= en-abstract= kn-abstract=Vasopressin/oxytocin (VP/OT)?related peptides are essential for mammalian antidiuresis, sociosexual behavior, and reproduction. However, the evolutionary origin of this peptide system is still uncertain. Here, we identify orthologous genes to those for VP/OT in Platyhelminthes, intertidal planarians that have a simple bilaterian body structure but lack a coelom and body-fluid circulatory system. We report a comprehensive characterization of the neuropeptide derived from this VP/OT-type gene, identifying its functional receptor, and name it the “platytocin” system. Our experiments with these euryhaline planarians, living where environmental salinities fluctuate due to evaporation and rainfall, suggest that platytocin functions as an “antidiuretic hormone” and also organizes diverse actions including reproduction and chemosensory-associated behavior. We propose that bilaterians acquired physiological adaptations to amphibious lives by such regulation of the body fluids. This neuropeptide-secreting system clearly became indispensable for life even without the development of a vascular circulatory system or relevant synapses. en-copyright= kn-copyright= en-aut-name=KobayashiAoshi en-aut-sei=Kobayashi en-aut-mei=Aoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamadaMayuko en-aut-sei=Hamada en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaMasa-aki en-aut-sei=Yoshida en-aut-mei=Masa-aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiYasuhisa en-aut-sei=Kobayashi en-aut-mei=Yasuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsutsuiNaoaki en-aut-sei=Tsutsui en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SekiguchiToshio en-aut-sei=Sekiguchi en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsukawaYuta en-aut-sei=Matsukawa en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaejimaSho en-aut-sei=Maejima en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GingellJoseph J. en-aut-sei=Gingell en-aut-mei=Joseph J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SekiguchiShoko en-aut-sei=Sekiguchi en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HamamotoAyumu en-aut-sei=Hamamoto en-aut-mei=Ayumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HayDebbie L. en-aut-sei=Hay en-aut-mei=Debbie L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MorrisJohn F. en-aut-sei=Morris en-aut-mei=John F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SakamotoTatsuya en-aut-sei=Sakamoto en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SakamotoHirotaka en-aut-sei=Sakamoto en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Oki Marine Biological Station, Shimane University kn-affil= affil-num=4 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Noto Marine Laboratory, Institute of Nature and Environmental Technology, Division of Marine Environmental Studies, Kanazawa University kn-affil= affil-num=7 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Vertex Pharmaceuticals (Europe) Ltd. kn-affil= affil-num=10 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=12 en-affil=School of Biological Sciences and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland kn-affil= affil-num=13 en-affil=Department of Physiology, Anatomy, and Genetic, Le Gros Clark Building, University of Oxford kn-affil= affil-num=14 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=15 en-affil=Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado kn-affil= END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=13 article-no= start-page=2519 end-page=2530 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Glass-patternable notch-shaped microwave architecture for on-chip spin detection in biological samples en-subtitle= kn-subtitle= en-abstract= kn-abstract=We report a notch-shaped coplanar microwave waveguide antenna on a glass plate designed for on-chip detection of optically detected magnetic resonance (ODMR) of fluorescent nanodiamonds (NDs). A lithographically patterned thin wire at the center of the notch area in the coplanar waveguide realizes a millimeter-scale ODMR detection area (1.5 × 2.0 mm2) and gigahertz-broadband characteristics with low reflection (?8%). The ODMR signal intensity in the detection area is quantitatively predictable by numerical simulation. Using this chip device, we demonstrate a uniform ODMR signal intensity over the detection area for cells, tissue, and worms. The present demonstration of a chip-based microwave architecture will enable scalable chip integration of ODMR-based quantum sensing technology into various bioassay platforms. en-copyright= kn-copyright= en-aut-name=OshimiKeisuke en-aut-sei=Oshimi en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraYushi en-aut-sei=Nishimura en-aut-mei=Yushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsubaraTsutomu en-aut-sei=Matsubara en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaMasuaki en-aut-sei=Tanaka en-aut-mei=Masuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShikohEiji en-aut-sei=Shikoh en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhaoLi en-aut-sei=Zhao en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZouYajuan en-aut-sei=Zou en-aut-mei=Yajuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KomatsuNaoki en-aut-sei=Komatsu en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkadoYuta en-aut-sei=Ikado en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakezawaYuka en-aut-sei=Takezawa en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=Kage-NakadaiEriko en-aut-sei=Kage-Nakadai en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IzutsuYumi en-aut-sei=Izutsu en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshizatoKatsutoshi en-aut-sei=Yoshizato en-aut-mei=Katsutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MoritaSaho en-aut-sei=Morita en-aut-mei=Saho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TokunagaMasato en-aut-sei=Tokunaga en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YukawaHiroshi en-aut-sei=Yukawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=BabaYoshinobu en-aut-sei=Baba en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TekiYoshio en-aut-sei=Teki en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FujiwaraMasazumi en-aut-sei=Fujiwara en-aut-mei=Masazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Graduate School of Science, Osaka City University kn-affil= affil-num=3 en-affil=Department of Anatomy and Regenerative Biology, Graduate School of Medicine, Osaka City University kn-affil= affil-num=4 en-affil=Department of Electrical and Information Engineering, Graduate School of Engineering, Osaka City University kn-affil= affil-num=5 en-affil=Department of Electrical and Information Engineering, Graduate School of Engineering, Osaka City University kn-affil= affil-num=6 en-affil=State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University kn-affil= affil-num=7 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Human and Environmental Studies, Kyoto University kn-affil= affil-num=9 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Department of Human Life Science, Graduate School of Food and Human Life Science, Osaka City University kn-affil= affil-num=11 en-affil=Department of Human Life Science, Graduate School of Food and Human Life Science, Osaka City University, kn-affil= affil-num=12 en-affil=Department of Biology, Faculty of Science, Niigata University kn-affil= affil-num=13 en-affil=Synthetic biology laboratory, Graduate school of medicine, Osaka City University kn-affil= affil-num=14 en-affil=Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University kn-affil= affil-num=15 en-affil=Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University kn-affil= affil-num=16 en-affil=Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University kn-affil= affil-num=17 en-affil=Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University kn-affil= affil-num=18 en-affil=Department of Chemistry, Graduate School of Science, Osaka City University kn-affil= affil-num=19 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=1 article-no= start-page=6 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=An approach for elucidating dermal fibroblast dedifferentiation in amphibian limb regeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Urodele amphibians, Pleurodeles waltl and Ambystoma mexicanum, have organ-level regeneration capability, such as limb regeneration. Multipotent cells are induced by an endogenous mechanism in amphibian limb regeneration. It is well known that dermal fibroblasts receive regenerative signals and turn into multipotent cells, called blastema cells. However, the induction mechanism of the blastema cells from matured dermal cells was unknown. We previously found that BMP2, FGF2, and FGF8 (B2FF) could play sufficient roles in blastema induction in urodele amphibians. Here, we show that B2FF treatment can induce dermis-derived cells that can participate in multiple cell lineage in limb regeneration. We first established a newt dermis-derived cell line and confirmed that B2FF treatment on the newt cells provided plasticity in cellular differentiation in limb regeneration. To clarify the factors that can provide the plasticity in differentiation, we performed the interspecies comparative analysis between newt cells and mouse cells and found the Pde4b gene was upregulated by B2FF treatment only in the newt cells. Blocking PDE4B signaling by a chemical PDE4 inhibitor suppressed dermis-to-cartilage transformation and the mosaic knockout animals showed consistent results. Our results are a valuable insight into how dermal fibroblasts acquire multipotency during the early phase of limb regeneration via an endogenous program in amphibian limb regeneration. en-copyright= kn-copyright= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KashimotoRena en-aut-sei=Kashimoto en-aut-mei=Rena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhashiAyaka en-aut-sei=Ohashi en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FurukawaSaya en-aut-sei=Furukawa en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoSakiya en-aut-sei=Yamamoto en-aut-mei=Sakiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InoueTakeshi en-aut-sei=Inoue en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HayashiToshinori en-aut-sei=Hayashi en-aut-mei=Toshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AgataKiyokazu en-aut-sei=Agata en-aut-mei=Kiyokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Research Core for Interdisciplinary Sciences (RCIS), Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Envi?ronmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Envi?ronmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Science, Department of Biological Sciences, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Science, Department of Biological Sciences, Okayama University kn-affil= affil-num=6 en-affil=Division of Adaptation Physiology, Faculty of Medicine, Tottori University kn-affil= affil-num=7 en-affil=Amphibian Research Center, Hiroshima University kn-affil= affil-num=8 en-affil=Laboratory of Regeneration Biology, National Institute for Basic Biology kn-affil= en-keyword=Pde4b kn-keyword=Pde4b en-keyword=Limb regeneration kn-keyword=Limb regeneration en-keyword=Pleurodels waltl kn-keyword=Pleurodels waltl en-keyword=Ambystoma mexicanum kn-keyword=Ambystoma mexicanum en-keyword=Dedifferentiation kn-keyword=Dedifferentiation en-keyword=Reprogramming kn-keyword=Reprogramming END start-ver=1.4 cd-journal=joma no-vol=128 cd-vols= no-issue= article-no= start-page=453 end-page=460 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220329 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Artificial selections for death-feigning behavior in beetles show correlated responses in amplitude of circadian rhythms, but the period of the rhythm does not en-subtitle= kn-subtitle= en-abstract= kn-abstract=One of the most important survival strategies of organisms is to avoid predators. Studying one of such strategies, namely, death-feigning behavior, has recently become more common. The success or failure of this antipredator strategy will be affected by the circadian rhythms of both prey and predator because death feigning sometimes has a diurnal rhythm. However, few studies have analyzed the effects of differences in circadian rhythms on predator-avoidance behavior at the genetic level. Recently, the relationship between genes relating to circadian rhythm and death-feigning behavior, an antipredator behavior, has been established at the molecular level. Therefore, in this study, we compared three circadian rhythm-related traits, the free-running period of rhythms, amplitude of circadian rhythms, and total activity of strains of three Tribolium species that were artificially selected for the death-feigning duration: short (S-strains) and long (L-strains) durations. As a result, the amplitude of circadian rhythms and total activity were significantly different between S- and L-strains, but there was no difference in the free-running periods of the rhythm between the strains in T. castaneum, T. confusum, and T. freemani. Although the relationship between death-feigning behavior and activity has been reported for all three species, a genetic relationship between the duration of death feigning and the amplitude of circadian rhythms has been newly found in the present study. It is important to investigate the relationship between antipredator strategies and circadian rhythms at the molecular level in the future. en-copyright= kn-copyright= en-aut-name=MiyatakeTakahisa en-aut-sei=Miyatake en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=S. AbeMasato en-aut-sei=S. Abe en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumuraKentarou en-aut-sei=Matsumura en-aut-mei=Kentarou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Center for Advanced Intelligence Project, RIKEN kn-affil= affil-num=3 en-affil=Laboratory of entomology, Faculty of Agriculture kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=biological clock kn-keyword=biological clock en-keyword=coleoptera kn-keyword=coleoptera en-keyword=death feigning kn-keyword=death feigning en-keyword=thanatosis kn-keyword=thanatosis en-keyword=tonic immobility kn-keyword=tonic immobility END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=2 article-no= start-page=203 end-page=215 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overexpression of Adenovirus E1A Reverses Transforming Growth Factor-β-induced Epithelial-mesenchymal Transition in Human Esophageal Cancer Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The epithelial-mesenchymal transition (EMT), a normal biological process by which epithelial cells acquire a mesenchymal phenotype, is associated with migration, metastasis, and chemoresistance in cancer cells, and with poor prognosis in patients with esophageal cancer. However, therapeutic strategies to inhibit EMT in tumor environments remain elusive. Here, we show the therapeutic potential of telomerase-specific replication- competent oncolytic adenovirus OBP-301 in human esophageal cancer TE4 and TE6 cells with an EMT phenotype. Transforming growth factor-β (TGF-β) administration induced the EMT phenotype with spindleshaped morphology, upregulation of mesenchymal markers and EMT transcription factors, migration, and chemoresistance in TE4 and TE6 cells. OBP-301 significantly inhibited the EMT phenotype via E1 accumulation. EMT cancer cells were susceptible to OBP-301 via massive autophagy induction. OBP-301 suppressed tumor growth and lymph node metastasis of TE4 cells co-inoculated with TGF-β-secreting fibroblasts. Our results suggest that OBP-301 inhibits the TGF-β-induced EMT phenotype in human esophageal cancer cells. OBP-301-mediated E1A overexpression is a promising antitumor strategy to inhibit EMT-mediated esophageal cancer progression. en-copyright= kn-copyright= en-aut-name=MasudaTomoya en-aut-sei=Masuda en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HashimotoYuuri en-aut-sei=Hashimoto en-aut-mei=Yuuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IedaTakeshi en-aut-sei=Ieda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Oncolys BioPharma Inc. kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=EMT kn-keyword=EMT en-keyword=TGF-β kn-keyword=TGF-β en-keyword=oncolytic adenovirus kn-keyword=oncolytic adenovirus en-keyword=E1A kn-keyword=E1A END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=2 article-no= start-page=87 end-page=92 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=2022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Confirmation of efficacy, elucidation of mechanism, and new search for indications of radon therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Indications of radon therapy include various diseases related to respiratory, painful, digestive, chronic degenerative, senile, etc. derived from reactive oxygen species, but most are based on empirical prescriptions. For this reason, we have evaluated the relation between the biological response caused by radon and the tissue/organ absorbed dose more quantitatively, and have promoted the elucidation of mechanisms related to the indication and searching newly. As a result, as a mechanism, a series of moderate physiological stimulative effects accompanying a small amount of oxidative stress by radon inhalation are being elucidated. That is, hyperfunction of anti-oxidation/immune regulation/damage repair, promotion of anti-inflammation/circulating metabolism/hormone secretion, induction of apoptosis/heat shock protein, etc. Also, new indications include inflammatory/neuropathic pain, hepatic/renal injury, colitis, type 1 diabetes, complication kidney injury, hyperuricemia, transient cerebral ischemia, and inflammatory edema. Furthermore, we examined the combined antioxidant effect of radon inhalation and antioxidants or therapeutic agents. As a result, it was clear that any combination treatment could enhance the suppression effect of disease. It can be expected that radon therapy can be used effectively by applying it in addition to usual treatment, since reduction in its dosage can also be expected by concomitant use for drugs with strong side effects. en-copyright= kn-copyright= en-aut-name=YamaokaKiyonori en-aut-sei=Yamaoka en-aut-mei=Kiyonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KataokaTakahiro en-aut-sei=Kataoka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Health Sciences, Institute of Academic and Research, Okayama University kn-affil= affil-num=2 en-affil=Health Sciences, Institute of Academic and Research, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=307 cd-vols= no-issue=2 article-no= start-page=198606 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A new tetra-segmented splipalmivirus with divided RdRP domains from Cryphonectria naterciae, a fungus found on chestnut and cork oak trees in Europe en-subtitle= kn-subtitle= en-abstract= kn-abstract=Positive-sense (+), single-stranded (ss) RNA viruses with divided RNA-dependent RNA polymerase (RdRP) domains have been reported from diverse filamentous ascomycetes since 2020. These viruses are termed splipalmiviruses or polynarnaviruses and have been characterized largely at the sequence level, but ill-defined biologically. Cryphonectria naterciae, from which only one virus has been reported, is an ascomycetous fungus potentially plant-pathogenic to chestnut and oak trees. We molecularly characterized multiple viruses in a single Portuguese isolate (C0614) of C. naterciae, taking a metatranscriptomic and conventional double-stranded RNA approach. Among them are a novel splipalmivirus (Cryphonectria naterciae splipalmivirus 1, CnSpV1) and a novel fusagravirus (Cryphonectria naterciae fusagravirus 1, CnFGV1). This study focused on the former virus. CnSpV1 has a tetra-segmented, (+)ssRNA genome (RNA1 to RNA4). As observed for other splipalmiviruses reported in 2020 and 2021, the RdRP domain is separately encoded by RNA1 (motifs F, A and B) and RNA2 (motifs C and D). A hypothetical protein encoded by the 5′-proximal open reading frame of RNA3 shows similarity to a counterpart conserved in some splipalmiviruses. The other RNA3-encoded protein and RNA4-encoded protein show no similarity with known proteins in a blastp search. The tetra-segment nature was confirmed by the conserved terminal sequences of the four CnSpV1 segments (RNA1 to RNA4) and their 100% coexistence in over 100 single conidial isolates tested. The experimental introduction of CnSpV1 along with CnFGV1 into a virus free strain C0754 of C. naterciae vegetatively incompatible with C0614 resulted in no phenotypic alteration, suggesting asymptomatic infection. The protoplast fusion assay indicates a considerably narrow host range of CnSpV1, restricted to the species C. naterciae and C. carpinicola. This study contributes to better understanding of the molecular and biological properties of this unique group of viruses. en-copyright= kn-copyright= en-aut-name=SatoYukiyo en-aut-sei=Sato en-aut-mei=Yukiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShahiSabitree en-aut-sei=Shahi en-aut-mei=Sabitree kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TelengechPaul en-aut-sei=Telengech en-aut-mei=Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HisanoSakae en-aut-sei=Hisano en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CornejoCarolina en-aut-sei=Cornejo en-aut-mei=Carolina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RiglingDaniel en-aut-sei=Rigling en-aut-mei=Daniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Swiss Federal Research Institute WSL, Forest Health & Biotic Interactions kn-affil= affil-num=6 en-affil=Swiss Federal Research Institute WSL, Forest Health & Biotic Interactions kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=8 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Splipalmivirus kn-keyword=Splipalmivirus en-keyword=Capsidless kn-keyword=Capsidless en-keyword=RNA virus kn-keyword=RNA virus en-keyword=Cryphonectria naterciae kn-keyword=Cryphonectria naterciae en-keyword=Narnavirus kn-keyword=Narnavirus en-keyword=Fungal virus kn-keyword=Fungal virus en-keyword=Mycovirus kn-keyword=Mycovirus END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=2 article-no= start-page=377 end-page=392 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel Prognostic Predictor of Immune Micro-environment and Therapeutic Response in Kidney Renal Clear Cell Carcinoma based on Necroptosis-related Gene Signature en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Necroptosis, a cell death of caspase-independence, plays a pivotal role in cancer biological regulation. Although necroptosis is closely associated with oncogenesis, cancer metastasis, and immunity, there remains a lack of studies determining the role of necroptosis-related genes (NRGs) in the highly immunogenic cancer type, kidney renal clear cell carcinoma (KIRC). Methods: The information of clinicopathology and transcriptome was extracted from TCGA database. Following the division into the train and test cohorts, a three-NRGs (TLR3, FASLG, ZBP1) risk model was identified in train cohort by LASSO regression. The overall survival (OS) comparison was conducted between different risk groups through Kaplan-Meier analysis, which was further validated in test cohort. The Cox proportional hazards regression model was introduced to assess its impact of clinicopathological factors and risk score on survival. ESTIMATE and CIBERSORT algorithms were introduced to evaluate immune microenvironment, while enrichment analysis was conducted to explore the biological significance. Correlation analysis was applied for the correlation assessment between checkpoint gene expression and risk score, between gene expression and therapeutic response. Gene expressions from TCGA were verified by GEO datasets and immunohistochemistry (IHC) analysis. Results: This NRGs-related signature predicted poorer OS in high-risk group, which was also verified in test cohort. Risk score could also independently predict survival outcome of KIRC. Significant changes were also found in immune microenvironment and checkpoint gene expressions between different risk groups, with immune functional enrichment in high-risk group. Interestingly, therapeutic response was correlated with the expressions of NRGs. The expressions of NRGs from TCGA were consistent with those from GEO datasets and IHC analysis. Conclusion: The NRGs-related signature functions as a novel prognostic predictor of immune microenvironment and therapeutic response in KIRC. en-copyright= kn-copyright= en-aut-name=ChenWenwei en-aut-sei=Chen en-aut-mei=Wenwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LinWenfeng en-aut-sei=Lin en-aut-mei=Wenfeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WuLiang en-aut-sei=Wu en-aut-mei=Liang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=XuAbai en-aut-sei=Xu en-aut-mei=Abai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiuChunxiao en-aut-sei=Liu en-aut-mei=Chunxiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HuangPeng en-aut-sei=Huang en-aut-mei=Peng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology, The First Affiliated Hospital, Wenzhou Medical University kn-affil= affil-num=4 en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University kn-affil= affil-num=5 en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=prognosis kn-keyword=prognosis en-keyword=immune microenvironment kn-keyword=immune microenvironment en-keyword=therapeutic response kn-keyword=therapeutic response en-keyword=kidney renal clear cell carcinoma kn-keyword=kidney renal clear cell carcinoma en-keyword=necroptosis kn-keyword=necroptosis en-keyword=gene signature kn-keyword=gene signature END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=3 article-no= start-page=1762 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220203 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aldehyde dehydrogenases (ALDHs) are the major enzyme superfamily for the aldehyde metabolism. Since the ALDH polymorphism leads to the accumulation of acetaldehyde, we considered that the enhancement of the liver ALDH activity by certain food ingredients could help prevent alcohol-induced chronic diseases. Here, we evaluated the modulating effects of 3-hydroxyphenylacetic acid (OPAC), the major metabolite of quercetin glycosides, on the ALDH activity and acetaldehyde-induced cytotoxicity in the cultured cell models. OPAC significantly enhanced the total ALDH activity not only in mouse hepatoma Hepa1c1c7 cells, but also in human hepatoma HepG2 cells. OPAC significantly increased not only the nuclear level of aryl hydrocarbon receptor (AhR), but also the AhR-dependent reporter gene expression, though not the nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent one. The pretreatment of OPAC at the concentration required for the ALDH upregulation completely inhibited the acetaldehyde-induced cytotoxicity. Silencing AhR impaired the resistant effect of OPAC against acetaldehyde. These results strongly suggested that OPAC protects the cells from the acetaldehyde-induced cytotoxicity, mainly through the AhR-dependent and Nrf2-independent enhancement of the total ALDH activity. Our findings suggest that OPAC has a protective potential in hepatocyte models and could offer a new preventive possibility of quercetin glycosides for targeting alcohol-induced chronic diseases. en-copyright= kn-copyright= en-aut-name=LiuYujia en-aut-sei=Liu en-aut-mei=Yujia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MyojinTakumi en-aut-sei=Myojin en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiKexin en-aut-sei=Li en-aut-mei=Kexin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KuritaAyuki en-aut-sei=Kurita en-aut-mei=Ayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SetoMasayuki en-aut-sei=Seto en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MotoyamaAyano en-aut-sei=Motoyama en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiuXiaoyang en-aut-sei=Liu en-aut-mei=Xiaoyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=MunemasaShintaro en-aut-sei=Munemasa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraToshiyuki en-aut-sei=Nakamura en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=School of Biological Engineering, Dalian Polytechnic University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=12 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=3-hydroxyphenylacetic acid kn-keyword=3-hydroxyphenylacetic acid en-keyword=aldehyde dehydrogenase kn-keyword=aldehyde dehydrogenase en-keyword=quercetin metabolites kn-keyword=quercetin metabolites en-keyword=aryl hydrocarbon receptor kn-keyword=aryl hydrocarbon receptor en-keyword=acetaldehyde kn-keyword=acetaldehyde END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=1 article-no= start-page=157 end-page=165 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Observing Phylum-Level Metazoan Diversity by Environmental DNA Analysis at the Ushimado Area in the Seto Inland Sea en-subtitle= kn-subtitle= en-abstract= kn-abstract=The dynamics of microscopic marine plankton in coastal areas is a fundamental theme in marine biodiversity research, but studies have been limited because the only available methodology was collection of plankton using plankton-nets and microscopic observation. In recent years, environmental DNA (eDNA) analysis has exhibited potential for conducting comprehensive surveys of marine plankton diversity in water at fixed points and depths in the ocean. However, few studies have examined how eDNA analysis reflects the actual distribution and dynamics of organisms in the field, and further investigation is needed to determine whether it can detect distinct differences in plankton density in the field. To address this, we analyzed eDNA in seawater samples collected at 1 km intervals at three depths over a linear distance of approximately 3.0 km in the Seto Inland Sea. The survey area included a location with a high density of Acoela (Praesagittifera naikaiensis). However, the eDNA signal for this was little to none, and its presence would not have been noticed if we did not have this information beforehand. Meanwhile, eDNA analysis enabled us to confirm the presence of a species of Placozoa that was previously undiscovered in the area. In summary, our results suggest that the number of sequence reads generated from eDNA samples in our project was not sufficient to predict the density of a particular species. However, eDNA can be useful for detecting organisms that have been overlooked using other methods. en-copyright= kn-copyright= en-aut-name=KawashimaTakeshi en-aut-sei=Kawashima en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshidaMasa-aki en-aut-sei=Yoshida en-aut-mei=Masa-aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyazawaHideyuki en-aut-sei=Miyazawa en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakanoHiroaki en-aut-sei=Nakano en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoNatumi en-aut-sei=Nakano en-aut-mei=Natumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakamotoTatsuya en-aut-sei=Sakamoto en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamadaMayuko en-aut-sei=Hamada en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=National Institute of Genetics kn-affil= affil-num=2 en-affil=Marine Biological Science Section, Education and Research Center Biological Resources, Faculty of Life and Environmental Science, Shimane University kn-affil= affil-num=3 en-affil=National Institute of Genetics kn-affil= affil-num=4 en-affil=Shimoda Marine Research Center, University of Tsukuba kn-affil= affil-num=5 en-affil=Department of Biology, Nara Medical University kn-affil= affil-num=6 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=7 en-affil=Ushimado Marine Institute, Okayama University kn-affil= en-keyword=eDNA kn-keyword=eDNA en-keyword=marine invertebrate kn-keyword=marine invertebrate en-keyword=Xenacoelomorpha kn-keyword=Xenacoelomorpha en-keyword=Acoela kn-keyword=Acoela en-keyword=Praesagittifera naikaiensis kn-keyword=Praesagittifera naikaiensis en-keyword=Placozoa kn-keyword=Placozoa en-keyword=Trichoplax adhaerens kn-keyword=Trichoplax adhaerens END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1 article-no= start-page=1 end-page=5 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mouse Model for Optogenetic Genome Engineering en-subtitle= kn-subtitle= en-abstract= kn-abstract=Optogenetics, a technology to manipulate biological phenomena thorough light, has attracted much attention in neuroscience. Recently, the Magnet System, a photo-inducible protein dimerization system which can control the intracellular behavior of various biomolecules with high accuracy using light was developed. Furthermore, photoactivation systems for controlling biological phenomena are being developed by combining this technique with genome-editing technology (CRISPR/Cas9 System) or DNA recombination technology (Cre-loxP system). Herein, we review the history of optogenetics and the latest Magnet System technology and introduce our recently developed photoactivatable Cre knock-in mice with temporal-, spatial-, and cell-specific accuracy. en-copyright= kn-copyright= en-aut-name=TakaoTomoka en-aut-sei=Takao en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaDaisuke en-aut-sei=Yamada en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaradaTakeshi en-aut-sei=Takarada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=optogenetics kn-keyword=optogenetics en-keyword=Cre recombinase kn-keyword=Cre recombinase END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=26 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220103 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Versatile Terahertz Chemical Microscope and Its Application for the Detection of Histamine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Terahertz waves have gained increasingly more attention because of their unique characteristics and great potential in a variety of fields. In this study, we introduced the recent progress of our versatile terahertz chemical microscope (TCM) in the detection of small biomolecules, ions, cancer cells, and antibody-antigen immunoassaying. We highlight the advantages of our TCM for chemical sensing and biosensing, such as label-free, high-sensitivity, rapid response, non-pretreatment, and minute amount sample consumption, compared with conventional methods. Furthermore, we demonstrated its new application in detection of allergic-related histamine at low concentration in buffer solutions. en-copyright= kn-copyright= en-aut-name=WangJin en-aut-sei=Wang en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoKosuke en-aut-sei=Sato en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaYuichi en-aut-sei=Yoshida en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaiKenji en-aut-sei=Sakai en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KiwaToshihiko en-aut-sei=Kiwa en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University 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=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=terahertz chemical microscope kn-keyword=terahertz chemical microscope en-keyword=potential distribution kn-keyword=potential distribution en-keyword=label-free kn-keyword=label-free en-keyword=biological substances kn-keyword=biological substances en-keyword=cancer cells kn-keyword=cancer cells en-keyword=antibody-antigen kn-keyword=antibody-antigen en-keyword=histamine kn-keyword=histamine END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=3 article-no= start-page=1214 end-page=1228 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of MICALL2 as a Novel Prognostic Biomarker Correlating with Inflammation and T Cell Exhaustion of Kidney Renal Clear Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: The interplay of inflammation and immunity affects all stages from tumorigenesis to progression, and even tumor response to therapy. A growing interest has been attracted from the biological function of MICALL2 to its effects on tumor progression. This study was designed to verify whether MICALL2 could be a prognostic biomarker to predict kidney renal clear cell carcinoma (KIRC) progression, inflammation, and immune infiltration within tumor microenvironment (TME).

Methods: We firstly analyzed MICALL2 expressions across 33 cancer types from the UCSC Xena database and verified its expression in KIRC through GEPIA platform and GEO datasets. The clinicopathological characteristics were further analyzed based on the median expression. Kaplan-Meier method, univariate and multivariate analyses were applied to compare survival outcomes. ESTIMATE and CIBERSORT algorithms were performed to assess immune infiltration, and a co-expression analysis was conducted to evaluate the correlation between MICALL2 and immunoregulatory genes. Enrichment analysis was finally performed to explore the biological significance of MICALL2.

Results: MICALL2 was highly expressed in 16 types of cancers compared with normal tissues. MICALL2 expression increased with advanced clinicopathological parameters and was an independent predictor for poor prognosis in KIRC. Moreover, MICALL2 closely correlated with inflammation-promoting signatures and immune infiltration including T cell exhaustion markers. Consistently, MICALL2 involved in the regulation of signaling pathways associated with tumor immunity, tumor progression, and impaired metabolic activities.

Conclusion: MICALL2 can function as a prognostic biomarker mediating inflammation, immune infiltration, and T cell exhaustion within the microenvironment of KIRC. en-copyright= kn-copyright= en-aut-name=LinWenfeng en-aut-sei=Lin en-aut-mei=Wenfeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChenWenwei en-aut-sei=Chen en-aut-mei=Wenwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhongJisheng en-aut-sei=Zhong en-aut-mei=Jisheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UekiHideo en-aut-sei=Ueki en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=XuAbai en-aut-sei=Xu en-aut-mei=Abai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LiuChunxiao en-aut-sei=Liu en-aut-mei=Chunxiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NasuYasutomo en-aut-sei=Nasu en-aut-mei=Yasutomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HuangPeng en-aut-sei=Huang en-aut-mei=Peng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University kn-affil= affil-num=3 en-affil=School of Medicine, Xiamen University kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Zhujiang Hospital, Southern Medical University kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=MICALL2 kn-keyword=MICALL2 en-keyword=biomarker kn-keyword=biomarker en-keyword=inflammation kn-keyword=inflammation en-keyword=T cell exhaustion kn-keyword=T cell exhaustion en-keyword=kidney renal clear cell carcinoma kn-keyword=kidney renal clear cell carcinoma END start-ver=1.4 cd-journal=joma no-vol=88 cd-vols= no-issue=2 article-no= start-page=105 end-page=127 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220117 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plant viruses and viroids in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=An increasing number of plant viruses and viroids have been reported from all over the world due largely to metavirogenomics approaches with technological innovation. Herein, the official changes of virus taxonomy, including the establishment of megataxonomy and amendments of the codes of virus classification and nomenclature, recently made by the International Committee on Taxonomy of Viruses were summarized. The continued efforts of the plant virology community of Japan to index all plant viruses and viroids occurring in Japan, which represent 407 viruses, including 303 virus species and 104 unclassified?viruses, and 25 viroids, including 20 species and 5 unclassified viroids, as of October 2021, were also introduced. These viruses and viroids are collectively classified into 81 genera within 26 families of 3 kingdoms (Shotokuvirae, Orthornavirae, Pararnavirae) across 2 realms (Monodnaviria and Riboviria). This review also overviewed how Japan’s plant virus/viroid studies have contributed to advance virus/viroid taxonomy. en-copyright= kn-copyright= en-aut-name=FujiShin-ichi en-aut-sei=Fuji en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MochizukiTomofumi en-aut-sei=Mochizuki en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkudaMitsuru en-aut-sei=Okuda en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsudaShinya en-aut-sei=Tsuda en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KagiwadaSatoshi en-aut-sei=Kagiwada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SekineKen-Taro en-aut-sei=Sekine en-aut-mei=Ken-Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UgakiMasashi en-aut-sei=Ugaki en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NatsuakiKeiko T. en-aut-sei=Natsuaki en-aut-mei=Keiko T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IsogaiMasamichi en-aut-sei=Isogai en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MaokaTetsuo en-aut-sei=Maoka en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakeshitaMinoru en-aut-sei=Takeshita en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshikawaNobuyuki en-aut-sei=Yoshikawa en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiseKazuyuki en-aut-sei=Mise en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SasayaTakahide en-aut-sei=Sasaya en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KubotaKenji en-aut-sei=Kubota en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamajiYasuyuki en-aut-sei=Yamaji en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IwanamiToru en-aut-sei=Iwanami en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OhshimaKazusato en-aut-sei=Ohshima en-aut-mei=Kazusato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KobayashiKappei en-aut-sei=Kobayashi en-aut-mei=Kappei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HatayaTatsuji en-aut-sei=Hataya en-aut-mei=Tatsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=SanoTeruo en-aut-sei=Sano en-aut-mei=Teruo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=SuzukiNobuhiro en-aut-sei=Suzuki en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Faculty of Bioresource Sciences, Akita Prefectural University kn-affil= affil-num=2 en-affil=Graduate School of Life and Environmental Sciences, Osaka Prefecture University kn-affil= affil-num=3 en-affil=Office of the President, National Agriculture and Food Research Organization (NARO) kn-affil= affil-num=4 en-affil=Department of Clinical Plant Science, Faculty of Bioscience and Applied Chemistry kn-affil= affil-num=5 en-affil=Department of Clinical Plant Science, Faculty of Bioscience and Applied Chemistry, Hosei University kn-affil= affil-num=6 en-affil=Faculty of Agriculture, University of the Ryukyus kn-affil= affil-num=7 en-affil=Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=8 en-affil=Tokyo University of Agriculture kn-affil= affil-num=9 en-affil=Faculty of Agriculture, Iwate University kn-affil= affil-num=10 en-affil=Institute for Plant Protection, National Agriculture and Food Research Organization (NIPP, NARO) kn-affil= affil-num=11 en-affil=Department of Agricultural and Environmental Sciences, Faculty of Agriculture, University of Miyazak kn-affil= affil-num=12 en-affil=Agri-Innovation Center, Iwate University kn-affil= affil-num=13 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=14 en-affil=3 Department of Research Promotion, Institute for Plant Protection, National Agriculture and Food Research Organization (NIPP, NARO) kn-affil= affil-num=15 en-affil=Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=16 en-affil=Division of Core Technology for Pest Control Research, Institute for Plant Protection, National Agriculture and Food Research Organization (NIPP, NARO) kn-affil= affil-num=17 en-affil=Department of Agricultural and Environmental Biology, Graduate School of Agricultural and Life Sciences, The University of Tokyo kn-affil= affil-num=18 en-affil=Faculty of Agriculture, Tokyo University of Agriculture kn-affil= affil-num=19 en-affil=Department of Biological Resource Science, Faculty of Agriculture, Saga University kn-affil= affil-num=20 en-affil=Faculty of Agriculture, Ehime University kn-affil= affil-num=21 en-affil=Research Faculty of Agriculture, Hokkaido University kn-affil= affil-num=22 en-affil=Hirosaki University kn-affil= affil-num=23 en-affil=Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue= article-no= start-page=71 end-page=86 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spred2 controls the severity of Concanavalin A-induced liver damage by limiting interferon-gamma production by CD4(+) and CD8(+) T cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Mitogen-activated protein kinases (MAPKs) are involved in T cell-mediated liver damage. However, the inhibitory mechanism(s) that controls T cell-mediated liver damage remains unknown. Objectives: We investigated whether Spred2 (Sprouty-related, EVH1 domain-containing protein 2) that negatively regulates ERK-MAPK pathway has a biological impact on T cell-mediated liver damage by using a murine model. Methods: We induced hepatotoxicity in genetically engineered mice by intravenously injecting Concanavalin A (Con A) and analyzed the mechanisms using serum chemistry, histology, ELISA, qRT-PCR, Western blotting and flow cytometry. Results: Spred2-deficient mice (Spred2(-/-)) developed more sever liver damage than wild-type (WT) mice with increased interferon-gamma (IFNy) production. Hepatic ERK phosphorylation was enhanced in Spred2(-/-) mice, and pretreatment of Spred2(-/-) mice with the MAPK/ERK inhibitor U0126 markedly inhibited the liver damage and reduced IFN gamma production. Neutralization of IFNy abolished the damage with decreased hepatic Stat1 activation in Spred2(-/-) mice. IFN gamma was mainly produced from CD4(+) and CD8(+) T cells, and their depletion decreased liver damage and IFN gamma production. Transplantation of CD4(+) and/or CD8(+) T cells from Spred2(-/-) mice into RAG1(-/-) mice deficient in both T and B cells caused more severe liver damage than those from WT mice. Hepatic expression of T cell attractants, CXCL9 and CXCL10, was augmented in Spred2(-/-) mice as compared to WT mice. Conversely, liver damage, IFN gamma production and the recruitment of CD4(+) and CD8(+) T cells in livers after Con A challenge were lower in Spred2 transgenic mice, and Spred2-overexpressing CD4(+) and CD8(+) T cells produced lower levels of IFN gamma than WT cells upon stimulation with Con A in vitro. Conclusion: We demonstrated, for the first time, that Spred2 functions as an endogenous regulator of T cell IFNy production and Spred2-mediated inhibition of ERK-MAPK pathway may be an effective remedy for T cell-dependent liver damage. en-copyright= kn-copyright= en-aut-name=SunCuiming en-aut-sei=Sun en-aut-mei=Cuiming 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=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiuQiuying en-aut-sei=Liu en-aut-mei=Qiuying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CaoChen en-aut-sei=Cao en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YangXu en-aut-sei=Yang en-aut-mei=Xu 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=KunkelSteven L. en-aut-sei=Kunkel en-aut-mei=Steven L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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 Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, 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, University of Michigan Medical School kn-affil= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Liver damage kn-keyword=Liver damage en-keyword=MAPK kn-keyword=MAPK en-keyword=Signal transduction and regulation kn-keyword=Signal transduction and regulation en-keyword=Gene-modified mice kn-keyword=Gene-modified mice en-keyword=Spred2 kn-keyword=Spred2 END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=11 article-no= start-page=1662 end-page=1675 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021827 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Small GTPase OsRac1 Forms Two Distinct Immune Receptor Complexes Containing the PRR OsCERK1 and the NLR Pit en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plants employ two different types of immune receptors, cell surface pattern recognition receptors (PRRs) and intracellular nucleotide-binding and leucine-rich repeat-containing proteins (NLRs), to cope with pathogen invasion. Both immune receptors often share similar downstream components and responses but it remains unknown whether a PRR and an NLR assemble into the same protein complex or two distinct receptor complexes. We have previously found that the small GTPase OsRac1 plays key roles in the signaling of OsCERK1, a PRR for fungal chitin, and of Pit, an NLR for rice blast fungus, and associates directly and indirectly with both of these immune receptors. In this study, using biochemical and bioimaging approaches, we revealed that OsRac1 formed two distinct receptor complexes with OsCERK1 and with Pit. Supporting this result, OsCERK1 and Pit utilized different transport systems for anchorage to the plasma membrane (PM). Activation of OsCERK1 and Pit led to OsRac1 activation and, concomitantly, OsRac1 shifted from a small to a large protein complex fraction. We also found that the chaperone Hsp90 contributed to the proper transport of Pit to the PM and the immune induction of Pit. These findings illuminate how the PRR OsCERK1 and the NLR Pit orchestrate rice immunity through the small GTPase OsRac1. en-copyright= kn-copyright= en-aut-name=AkamatsuAkira en-aut-sei=Akamatsu en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasayuki en-aut-sei=Fujiwara en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaSatoshi en-aut-sei=Hamada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WakabayashiMegumi en-aut-sei=Wakabayashi en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YaoAi en-aut-sei=Yao en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WangQiong en-aut-sei=Wang en-aut-mei=Qiong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KosamiKen-ichi en-aut-sei=Kosami en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=DangThu Thi en-aut-sei=Dang en-aut-mei=Thu Thi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Kaneko-KawanoTakako en-aut-sei=Kaneko-Kawano en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukadaFumi en-aut-sei=Fukada en-aut-mei=Fumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShimamotoKo en-aut-sei=Shimamoto en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawanoYoji en-aut-sei=Kawano en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Biosciences, Kwansei Gakuin University kn-affil= affil-num=2 en-affil=Graduate School of Biological Sciences, Nara Institute of Science and Technology kn-affil= affil-num=3 en-affil=Graduate School of Biological Sciences, Nara Institute of Science and Technology kn-affil= affil-num=4 en-affil=Graduate School of Biological Sciences, Nara Institute of Science and Technology kn-affil= affil-num=5 en-affil=Graduate School of Biological Sciences, Nara Institute of Science and Technology kn-affil= affil-num=6 en-affil=Department of Horticulture and Plant Protection kn-affil= affil-num=7 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Shanghai Center for Plant Stress Biology, Chinese Academy of Sciences kn-affil= affil-num=8 en-affil=Graduate School of Biological Sciences, Nara Institute of Science and Technology kn-affil= affil-num=9 en-affil=College of Pharmaceutical Sciences, Ritsumeikan University kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources kn-affil= affil-num=11 en-affil=Graduate School of Biological Sciences, Nara Institute of Science and Technology kn-affil= affil-num=12 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue= article-no= start-page=794948 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exploring the Retinal Binding Cavity of Archaerhodopsin-3 by Replacing the Retinal Chromophore With a Dimethyl Phenylated Derivative en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rhodopsins act as photoreceptors with their chromophore retinal (vitamin-A aldehyde) and they regulate light-dependent biological functions. Archaerhodopsin-3 (AR3) is an outward proton pump that has been widely utilized as a tool for optogenetics, a method for controlling cellular activity by light. To characterize the retinal binding cavity of AR3, we synthesized a dimethyl phenylated retinal derivative, (2E,4E,6E,8E)-9-(2,6-Dimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenal (DMP-retinal). QM/MM calculations suggested that DMP-retinal can be incorporated into the opsin of AR3 (archaeopsin-3, AO3). Thus, we introduced DMP-retinal into AO3 to obtain the non-natural holoprotein (AO3-DMP) and compared some molecular properties with those of AO3 with the natural A1-retinal (AO3-A1) or AR3. Light-induced pH change measurements revealed that AO3-DMP maintained slow outward proton pumping. Noteworthy, AO3-DMP had several significant changes in its molecular properties compared with AO3-A1 as follows; 1) spectroscopic measurements revealed that the absorption maximum was shifted from 556 to 508 nm and QM/MM calculations showed that the blue-shift was due to the significant increase in the HOMO-LUMO energy gap of the chromophore with the contribution of some residues around the chromophore, 2) time-resolved spectroscopic measurements revealed the photocycling rate was significantly decreased, and 3) kinetical spectroscopic measurements revealed the sensitivity of the chromophore binding Schiff base to attack by hydroxylamine was significantly increased. The QM/MM calculations show that a cavity space is present at the aromatic ring moiety in the AO3-DMP structure whereas it is absent at the corresponding beta-ionone ring moiety in the AO3-A1 structure. We discuss these alterations of the difference in interaction between the natural A1-retinal and the DMP-retinal with binding cavity residues. en-copyright= kn-copyright= en-aut-name=TsuneishiTaichi en-aut-sei=Tsuneishi en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiMasataka en-aut-sei=Takahashi en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujimuraMasaki en-aut-sei=Tsujimura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=TakeuchiYasuo en-aut-sei=Takeuchi en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= affil-num=1 en-affil=Laboratory of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Laboratory of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry, The University of Tokyo kn-affil= affil-num=4 en-affil=Laboratory of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Applied Chemistry, The University of Tokyo kn-affil= affil-num=6 en-affil=Laboratory of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Laboratory of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=retinal kn-keyword=retinal en-keyword=rhodopsin kn-keyword=rhodopsin en-keyword=proton pump kn-keyword=proton pump en-keyword=derivative kn-keyword=derivative en-keyword=photoreceptor kn-keyword=photoreceptor END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=6 article-no= start-page=838 end-page=845 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Marginal Sufficient Component Cause Model - An Emerging Causal Model With Merits? en-subtitle= kn-subtitle= en-abstract= kn-abstract=For decades, the sufficient cause model and the counterfactual model have shaped our understanding of causation in biomedical science, and the link between these two models has enabled us to obtain a deeper understanding of causality. Recently, a new causal model?the marginal sufficient component cause model?was proposed and applied in the context of interaction or mediation. The proponents of this model have emphasized its utility in visualizing the presence of “agonism” (a subtype of mechanistic interaction) in the counterfactual framework, claiming that the concept of agonism has not been clearly defined in causal inference and that agonistic interaction cannot be visualized by the conventional sufficient cause model. In this article, we illustrate that careful scrutiny based on the conventional sufficient cause model yields further insights into the concept of agonism in a more biologic sense. We primarily focus on the following three points: a) “agonism” defined in the counterfactual model can be visualized as sets of sufficient causes in the conventional sufficient cause model; b) although the so-called independent competing assumption or no redundancy assumption may seem irrelevant in the marginal sufficient component cause model, researchers do need to assume that potential completion times of relevant marginal sufficient causes differ; c) possibly differing potential completion times of marginal sufficient causes cannot be discerned until their hidden mechanistic paths are considered in the conventional sufficient cause model. In this rapidly progressing field of research, decades after its introduction, the sufficient cause model retains its worth. en-copyright= kn-copyright= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoEiji en-aut-sei=Yamamoto en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Okayama University of Science kn-affil= en-keyword=Agonism kn-keyword=Agonism en-keyword=Causality kn-keyword=Causality en-keyword=Counterfactual model kn-keyword=Counterfactual model en-keyword=Mediation kn-keyword=Mediation en-keyword=Potential outcomes kn-keyword=Potential outcomes en-keyword=Sufficient cause model kn-keyword=Sufficient cause model END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=12 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Proton beam therapy followed by pembrolizumab for giant ocular surface conjunctival malignant melanoma: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=The present study describes proton beam therapy as a clinical option to achieve local control of giant conjunctival melanoma in an aged person, instead of orbital exenteration. An 80?year?old woman with one?year history of left?eye injection and hemorrhage experienced rapid growth of the ocular surface black mass. At the initial visit, a black, elastic hard, hemorrhage?prone, thickened mass in the size of 30x40 mm with a presumed wide stalk covered the total area of the lid fissure on the left side. Biopsy of the mass demonstrated anomalous melanin?containing cells in fibrin and hemorrhage, which were positive for cocktail?mix antibodies against tyrosinase, melanoma antigen recognized by T cells?1 and human melanoma black?45, indicative of malignant melanoma. One month after the initial visit, the patient underwent proton beam therapy at the total dose of 70.4 Gy (relative biological effectiveness) in 32 fractions (~10 min each) in one and a half months. One month after the end of proton beam therapy, 3.5 months from the initial visit, the patient was found by computed tomographic scan to have multiple metastatic lesions in bilateral lung fields. With the evidence of absent BRAF mutation, the patient underwent intravenous administration of pembrolizumab 77.2 mg every three weeks five times in total. Then, three months after proton beam therapy, ocular surface melanoma almost subsided and the clear cornea allowed visualization of the intraocular lens inside the eye. In three weeks, spontaneous corneal perforation was plugged with iris incarceration. The patient died suddenly of unknown cause 7.5 months from the initial visit. The local control of giant conjunctival melanoma was achieved by proton beam therapy, leading to patient's satisfaction and better quality of life. Proton beam therapy, followed by immune checkpoint inhibitors, would become the future standard of care for unresectable giant conjunctival melanoma. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsuiKuniaki en-aut-sei=Katsui en-aut-mei=Kuniaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WakiTakahiro en-aut-sei=Waki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Regenerative and Reconstructive Medicine (Ophthalmology), Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Radiation Oncology, Department of Radiology, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Radiology, Tsuyama Chuo Hospital kn-affil= en-keyword=ocular surface kn-keyword=ocular surface en-keyword=conjunctiva kn-keyword=conjunctiva en-keyword=malignant melanoma kn-keyword=malignant melanoma en-keyword=proton beam therapy kn-keyword=proton beam therapy en-keyword=pembrolizumab kn-keyword=pembrolizumab en-keyword=PD?1 inhibitor kn-keyword=PD?1 inhibitor en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=corneal perforation kn-keyword=corneal perforation END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=11 article-no= start-page=e003134 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Patients with cancer benefit from treatment with immune checkpoint inhibitors (ICIs), and those with an inflamed tumor microenvironment (TME) and/or high tumor mutation burden (TMB), particularly, tend to respond to ICIs; however, some patients fail, whereas others acquire resistance after initial response despite the inflamed TME and/or high TMB. We assessed the detailed biological mechanisms of resistance to ICIs such as programmed death 1 and/or cytotoxic T-lymphocyte-associated protein 4 blockade therapies using clinical samples.

Methods
We established four pairs of autologous tumor cell lines and tumor-infiltrating lymphocytes (TILs) from patients with melanoma treated with ICIs. These tumor cell lines and TILs were subjected to comprehensive analyses and in vitro functional assays. We assessed tumor volume and TILs in vivo mouse models to validate identified mechanism. Furthermore, we analyzed additional clinical samples from another large melanoma cohort.

Results
Two patients were super-responders, and the others acquired resistance: the first patient had a non-inflamed TME and acquired resistance due to the loss of the beta-2 microglobulin gene, and the other acquired resistance despite having inflamed TME and extremely high TMB which are reportedly predictive biomarkers. Tumor cell line and paired TIL analyses showed high CD155, TIGIT ligand, and TIGIT expression in the tumor cell line and tumor-infiltrating T cells, respectively. TIGIT blockade or CD155-deletion activated T cells in a functional assay using an autologous cell line and paired TILs from this patient. CD155 expression increased in surviving tumor cells after coculturing with TILs from a responder, which suppressed TIGIT+ T-cell activation. Consistently, TIGIT blockade or CD155-deletion could aid in overcoming resistance to ICIs in vivo mouse models. In clinical samples, CD155 was related to resistance to ICIs in patients with melanoma with an inflamed TME, including both primary and acquired resistance.

Conclusions
The TIGIT/CD155 axis mediates resistance to ICIs in patients with melanoma with an inflamed TME, promoting the development of TIGIT blockade therapies in such patients with cancer. en-copyright= kn-copyright= en-aut-name=KawashimaShusuke en-aut-sei=Kawashima en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UenoToshihide en-aut-sei=Ueno en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanjiEtsuko en-aut-sei=Tanji en-aut-mei=Etsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HonobeAkiko en-aut-sei=Honobe en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhnumaTakehiro en-aut-sei=Ohnuma en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UmedaYoshiyasu en-aut-sei=Umeda en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraYasuhiro en-aut-sei=Nakamura en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawasakiTomonori en-aut-sei=Kawasaki en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KiniwaYukiko en-aut-sei=Kiniwa en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FukushimaSatoshi en-aut-sei=Fukushima en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=IkeharaYuzuru en-aut-sei=Ikehara en-aut-mei=Yuzuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SuzukiYutaka en-aut-sei=Suzuki en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=NishikawaHiroyoshi en-aut-sei=Nishikawa en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MatsueHiroyuki en-aut-sei=Matsue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Research Institute, Chiba Cancer Center kn-affil= affil-num=2 en-affil=Research Institute, Chiba Cancer Center kn-affil= affil-num=3 en-affil=Research Institute, Chiba Cancer Center kn-affil= affil-num=4 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=5 en-affil=Research Institute, Chiba Cancer Center kn-affil= affil-num=6 en-affil=Research Institute, Chiba Cancer Center kn-affil= affil-num=7 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=8 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=9 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=10 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=11 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=12 en-affil=Department of Pathology, Saitama Medical University International Medical Center kn-affil= affil-num=13 en-affil=Department of Dermatology, Shinshu University School of Medicine kn-affil= affil-num=14 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University kn-affil= affil-num=16 en-affil=Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=18 en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo kn-affil= affil-num=19 en-affil=Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center kn-affil= affil-num=20 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=多様な菌類および植物パルティティウイルスの分子生物学的・生物学的性状 kn-title=Molecular and biological properties of diverse fungal and plant partitiviruses en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TELENGECH Paul Kipkemboi en-aut-sei=TELENGECH Paul Kipkemboi en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil=岡山大学大学院環境生命科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=生物学的に活性な抗酸化物質の豊富な供給源としての米エタノール抽出物の評価 kn-title=Evaluation and classification of rice ethanol extracts as a rich source of biologically-active antioxidants en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WuHongyan en-aut-sei=Wu en-aut-mei=Hongyan kn-aut-name=呉虹燕 kn-aut-sei=呉 kn-aut-mei=虹燕 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil=岡山大学大学院環境生命科学研究科 END start-ver=1.4 cd-journal=joma no-vol=170 cd-vols= no-issue=3 article-no= start-page=435 end-page=443 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Unusual aggregation property of recombinantly expressed cancer-testis antigens in mammalian cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Transient expression of human intracellular proteins in human embryonic kidney (HEK) 293 cells is a reliable system for obtaining soluble proteins with biologically active conformations. Contrary to conventional concepts, we found that recombinantly expressed intracellular cancer-testis antigens (CTAs) showed frequent aggregation in HEK293 cells. Although experimental subcellular localization of recombinant CTAs displayed proper cytosolic or nuclear localization, some proteins showed aggregated particles in the cell. This aggregative property was not observed in recombinant housekeeping proteins. No significant correlation was found between the aggregative and biophysical properties, such as hydrophobicity, contents of intrinsically disordered regions and expression levels, of CTAs. These results can be explained in terms of structural instability of CTAs, which are specifically expressed in the testis and aberrantly expressed in cancer cells and function as a hub in the protein?protein network using intrinsically disordered regions. Hence, we speculate that recombinantly expressed CTAs failed to form this protein complex. Thus, unfolded CTAs formed aggregated particles in the cell. en-copyright= kn-copyright= en-aut-name=AhmadiHannaneh en-aut-sei=Ahmadi en-aut-mei=Hannaneh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShogenKohei en-aut-sei=Shogen en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujitaKana en-aut-sei=Fujita en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HonjoTomoko en-aut-sei=Honjo en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KakimiKazuhiro en-aut-sei=Kakimi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Immunotherapeutics, The University of Tokyo Hospital kn-affil= affil-num=6 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=339 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background : Acute respiratory distress syndrome, which is caused by acute lung injury, is a destructive respiratory disorder caused by a systemic inflammatory response. Persistent inflammation results in irreversible alveolar fibrosis. Because hydrogen gas possesses anti-inflammatory properties, we hypothesized that daily repeated inhalation of hydrogen gas could suppress persistent lung inflammation by inducing functional changes in macrophages, and consequently inhibit lung fibrosis during late-phase lung injury.
Methods : To test this hypothesis, lung injury was induced in mice by intratracheal administration of bleomycin (1.0 mg/kg). Mice were exposed to control gas (air) or hydrogen (3.2% in air) for 6 h every day for 7 or 21 days. Respiratory physiology, tissue pathology, markers of inflammation, and macrophage phenotypes were examined.
Results : Mice with bleomycin-induced lung injury that received daily hydrogen therapy for 21 days (BH group) exhibited higher static compliance (0.056 mL/cmH(2)O, 95% CI 0.047-0.064) than mice with bleomycin-induced lung injury exposed only to air (BA group; 0.042 mL/cmH(2)O, 95% CI 0.031-0.053, p = 0.02) and lower static elastance (BH 18.8 cmH(2)O/mL, [95% CI 15.4-22.2] vs. BA 26.7 cmH(2)O/mL [95% CI 19.6-33.8], p = 0.02). When the mRNA levels of pro-inflammatory cytokines were examined 7 days after bleomycin administration, interleukin (IL)-6, IL-4 and IL-13 were significantly lower in the BH group than in the BA group. There were significantly fewer M2-biased macrophages in the alveolar interstitium of the BH group than in the BA group (3.1% [95% CI 1.6-4.5%] vs. 1.1% [95% CI 0.3-1.8%], p = 0.008).
Conclusions The results suggest that hydrogen inhalation inhibits the deterioration of respiratory physiological function and alveolar fibrosis in this model of lung injury. en-copyright= kn-copyright= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SeyaMizuki en-aut-sei=Seya en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IketaniMasumi en-aut-sei=Iketani en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IshikawaMichiko en-aut-sei=Ishikawa en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TerasakiYasuhiro en-aut-sei=Terasaki en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhsawaIkuroh en-aut-sei=Ohsawa en-aut-mei=Ikuroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Disaster Medicine and Management, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Primary Care and Medical Education, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=6 en-affil=Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine kn-affil= affil-num=7 en-affil=Department of Analytic Human Pathology, Nippon Medical School kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=10 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Acute respiratory distress syndrome kn-keyword=Acute respiratory distress syndrome en-keyword=Bleomycin-induced lung injury kn-keyword=Bleomycin-induced lung injury en-keyword=Macrophage kn-keyword=Macrophage en-keyword=Molecular hydrogen kn-keyword=Molecular hydrogen en-keyword=Lung fibrosis kn-keyword=Lung fibrosis END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=10 article-no= start-page=1357 end-page=1363 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Microbial Rhodopsins as Multi-functional Photoreactive Membrane Proteins for Optogenetics en-subtitle= kn-subtitle= en-abstract= kn-abstract=In life science research, methods to control biological activities with stimuli such as light, heat, pressure and chemicals have been widely utilized to understand their molecular mechanisms. The knowledge obtained by those methods has built a basis for the development of medicinal products. Among those various stimuli, light has the advantage of a high spatiotemporal resolution that allows for the precise control of biological activities. Photoactive membrane protein rhodopsins from microorganisms (called microbial rhodopsins) absorb visible light and that light absorption triggers the trans?cis photoisomerization of the chromophore retinal, leading to various functions such as ion pumps, ion channels, transcriptional regulators and enzymes. In addition to their biological significance, microbial rhodopsins are widely utilized as fundamental molecular tools for optogenetics, a method to control biological activities by light. In this review, we briefly introduce the molecular basis of representative rhodopsin molecules and their applications for optogenetics. Based on those examples, we discuss the high potential of rhodopsin-based optogenetics tools for basic and clinical research in pharmaceutical sciences. en-copyright= kn-copyright= en-aut-name=NakaoShin en-aut-sei=Nakao en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= affil-num=1 en-affil=Division of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=rhodopsin kn-keyword=rhodopsin en-keyword=optogenetics kn-keyword=optogenetics en-keyword=retinal kn-keyword=retinal en-keyword=signal transduction kn-keyword=signal transduction END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue= article-no= start-page=101404 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Production of TRPM4 knockout cell line using rat cardiomyocyte H9c2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The method presented in this article are related to the research article entitled as "Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress" [1]. TRPM4, a non-selective monovalent cation channel, is not only involved in the generation of the action potential in cardiomyocytes, but also thought to be a key molecule in the development of the ischemia-reperfusion injury of the brain and the heart [2-5]. However, existing pharmacological inhibitors for the TRPM4 channel have problems of non-specificity [6]. This article describes methods used for targeted genomic deletion in the rat cardiomyocyte H9c2 using the CRISPR-Cas9 genome editing system in order to suppress TRPM4 protein expression. Confocal microscopy, flow cytometry, Sanger sequencing, and western blotting are performed to confirm vector transfection and the subsequent knockout of the TRPM4 protein. These data provide information on the comprehensive analyses for knocking out the rat TRPM4 channel using CRISPR/Cas9. The analyses include confocal microscopy, flow cytometry, Sanger sequencing, and western blotting. This dataset will benefit biological and medical researchers studying the function of TRPM4-expressing cells including neurons, cardiomyocytes, and vascular endothelial cells. It is also useful to study the involvement of the TRPM4 channel in pathological processes such as cardiac arrhythmia and ischemia-reperfusion injury. The dataset can be used to guide the experiment of knocking out the TRPM4 gene and its subsequent application to the study of disease process caused by the gene. en-copyright= kn-copyright= en-aut-name=WangChen en-aut-sei=Wang en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaMasakazu en-aut-sei=Maeda en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChenJian en-aut-sei=Chen en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangMengxue en-aut-sei=Wang en-aut-mei=Mengxue 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= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medicine, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=TRPM4 kn-keyword=TRPM4 en-keyword=Cardiomyocyte kn-keyword=Cardiomyocyte en-keyword=H9c2 kn-keyword=H9c2 en-keyword=CRISPR/Cas9 kn-keyword=CRISPR/Cas9 en-keyword=Confocal microscopy kn-keyword=Confocal microscopy en-keyword=DNA sequencing kn-keyword=DNA sequencing en-keyword=Flow cytometry kn-keyword=Flow cytometry en-keyword=Western blotting kn-keyword=Western blotting END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=6 article-no= start-page=759 end-page=762 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pulmonary Enteric Adenocarcinoma Harboring a BRAF G469V Mutation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of lung cancer that should be differentiated from colorectal cancer metastasis. Little is known about its genetic background. An 84-year-old male with adenocarcinoma of the lung underwent left upper lobectomy. The histology of the surgical specimen was suggestive of PEAC. Gastrointestinal and colorectal fiberscopy revealed no evidence of colorectal cancer. Next-generation sequencing of the tumor identified a G469V substitution in serine/threonine-protein kinase B-raf (BRAF). Based on the higher prevalence of the G469 substitution in BRAF-mutant lung adenocarcinoma than in BRAFmutant colorectal cancer, the tumor likely originated from the lung. Identification of mutational genotype may be of some help in distinguishing PEAC from the lung metastasis of colorectal cancer. en-copyright= kn-copyright= en-aut-name=ShimizuDai en-aut-sei=Shimizu en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniguchiKohei en-aut-sei=Taniguchi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=NambaKei en-aut-sei=Namba en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MesakiKumi en-aut-sei=Mesaki en-aut-mei=Kumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=SohJunichi en-aut-sei=Soh en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Diagnostic Pathology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=somatic mutations kn-keyword=somatic mutations en-keyword=pulmonary adenocarcinoma with enteric differentiation kn-keyword=pulmonary adenocarcinoma with enteric differentiation en-keyword=non-V600E BRAF mutation kn-keyword=non-V600E BRAF mutation en-keyword=next-generation sequencing kn-keyword=next-generation sequencing END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=6 article-no= start-page=713 end-page=718 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Correlations Among Consistency, Computed Tomography Values, and Histopathological Subtypes of Spinal Meningioma en-subtitle= kn-subtitle= en-abstract= kn-abstract=The consistency of spinal meningiomas is important to consider when performing tumor removal surgery. This study evaluated the correlations between spinal meningioma consistency and both preoperative computed tomography (CT) values and histopathological subtypes. Fifteen consecutive patients who underwent surgical resection of spinal meningioma at our institution were identified, and preoperative CT values and the signal intensity of T2-weighted magnetic resonance images of the tumor were determined retrospectively. The consistency of the spinal meningioma was defined based on the ultrasonic surgical aspirator output during tumor debulking. Patients were assigned to 2 groups: a soft group (n=4) and a hard group (n=11). The T2 signal intensity was significantly higher in the soft group than in the hard group (p=0.001). While the CT values were considerably higher in the hard group, the difference was not significant (p=0.19). Regarding the histopathological subtypes, psammomatous meningioma exhibited significantly higher CT values than meningothelial meningioma (p=0.019); however, there was a higher frequency of hard tumors in meningothelial meningioma cases than in psammomatous meningioma cases. Although neither robust correlations between tumor consistency and CT values nor a relationship between tumor consistency and histopathological subtype has been established, these results might help with the perioperative manegement of spinal tumors. en-copyright= kn-copyright= en-aut-name=AoyamaTatsuro en-aut-sei=Aoyama en-aut-mei=Tatsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgiwaraToshihiro en-aut-sei=Ogiwara en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ItoKiyoshi en-aut-sei=Ito en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyaokaYoshinari en-aut-sei=Miyaoka en-aut-mei=Yoshinari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiiYu en-aut-sei=Fujii en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HanaokaYoshiki en-aut-sei=Hanaoka en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HasegawaTakatoshi en-aut-sei=Hasegawa en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WatanabeGen en-aut-sei=Watanabe en-aut-mei=Gen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SeguchiTatsuya en-aut-sei=Seguchi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HongoKazuhiro en-aut-sei=Hongo en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neurosurgery, Shinshu University School of Medicine kn-affil= affil-num=2 en-affil=Department of Neurosurgery, Shinshu University School of Medicine kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Shinshu University School of Medicine kn-affil= affil-num=4 en-affil=Department of Neurosurgery, Shinshu University School of Medicine kn-affil= affil-num=5 en-affil=Department of Neurosurgery, Shinshu University School of Medicine kn-affil= affil-num=6 en-affil=Department of Neurosurgery, Shinshu University School of Medicine kn-affil= affil-num=7 en-affil=Department of Neurosurgery, Shinshu University School of Medicine kn-affil= affil-num=8 en-affil=Department of Neurosurgery, Shinshu University School of Medicine kn-affil= affil-num=9 en-affil=Department of Neurosurgery, Seguchi Neurosurgical Hospital kn-affil= affil-num=10 en-affil=Department of Neurosurgery, Shinshu University School of Medicine kn-affil= en-keyword=calcification kn-keyword=calcification en-keyword=computed tomography kn-keyword=computed tomography en-keyword=psammoma body kn-keyword=psammoma body en-keyword=spinal meningioma kn-keyword=spinal meningioma END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=6 article-no= start-page=699 end-page=704 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Guideline-based Treatment of Glucocorticoid-induced Osteoporosis in Patients with Rheumatoid Arthritis: A Retrospective Study with the AORA Registry en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glucocorticoid-induced osteoporosis (GIOP) is one of the side effects associated with glucocorticoid (GC) therapy. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) provided new guidelines for the management and treatment of GIOP. The aim of the present study was to clarify the prevalence of patients with rheumatoid arthritis (RA) requiring treatment according to the new guidelines and to identify risk factors associated with lack of treatment in these patients. Patients in the 2018 Akita Orthopedic group on Rheumatoid Arthritis (AORA) database were enrolled. Of 2,234 patients with RA in the database, 683 (30.6%) met the 2014 JSBMR guideline treatment criteria, and 480 (70.3%) had been treated. The untreated group included a larger number of males, younger patients, and patients treated in clinics rather than hospital (p<0.001, p=0.015, and p<0.001, respectively). Multivariate analyses found that male sex, younger age, and clinic-based RA care were significant risk factors associated with lack of treatment (p<0.001, p=0.013, and p<0.001, respectively). Thus, male sex, younger age, and clinic-based care were identified as risk factors en-copyright= kn-copyright= en-aut-name=KawanoTetsuya en-aut-sei=Kawano en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyakoshiNaohisa en-aut-sei=Miyakoshi en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchieHiroyuki en-aut-sei=Tsuchie en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KashiwaguraTakeshi en-aut-sei=Kashiwagura en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiMoto en-aut-sei=Kobayashi en-aut-mei=Moto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AonumaHiroshi en-aut-sei=Aonuma en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugimuraYusuke en-aut-sei=Sugimura en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimadaYoichi en-aut-sei=Shimada en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Akita City Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Hiraka General Hospital Yokote City kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Ogachi Central Hospital Yuzawa City kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Nakadori General Hospital Akita City kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Akita University Graduate School of Medicine kn-affil= en-keyword=glucocorticoid kn-keyword=glucocorticoid en-keyword=glucocorticoid-induced osteoporosis kn-keyword=glucocorticoid-induced osteoporosis en-keyword=rheumatoid arthritis kn-keyword=rheumatoid arthritis en-keyword=osteoporosis kn-keyword=osteoporosis en-keyword=osteopenia kn-keyword=osteopenia END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=5 article-no= start-page=549 end-page=556 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Glial Cells as Possible Targets of Neuroprotection through Neurotrophic and Antioxidative Molecules in the Central and Enteric Nervous Systems in Parkinson’s Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. The loss of nigrostriatal dopaminergic neurons produces its characteristic motor symptoms, but PD patients also have non-motor symptoms such as constipation and orthostatic hypotension. The pathological hallmark of PD is the presence of α-synuclein-containing Lewy bodies and neurites in the brain. However, the PD pathology is observed in not only the central nervous system (CNS) but also in parts of the peripheral nervous system such as the enteric nervous system (ENS). Since constipation is a typical prodromal non-motor symptom in PD, often preceding motor symptoms by 10-20 years, it has been hypothesized that PD pathology propagates from the ENS to the CNS via the vagal nerve. Discovery of pharmacological and other methods to halt this progression of neurodegeneration in PD has the potential to improve millions of lives. Astrocytes protect neurons in the CNS by secretion of neurotrophic and antioxidative factors. Similarly, astrocyte-like enteric glial cells (EGCs) are known to secrete neuroprotective factors in the ENS. In this article, we summarize the neuroprotective function of astrocytes and EGCs and discuss therapeutic strategies for the prevention of neurodegeneration in PD targeting neurotrophic and antioxidative molecules in glial cells. en-copyright= kn-copyright= en-aut-name=IsookaNami en-aut-sei=Isooka en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Parkinson’s disease kn-keyword=Parkinson’s disease en-keyword=astrocyte kn-keyword=astrocyte en-keyword=enteric glial cell kn-keyword=enteric glial cell en-keyword=neurotrophic factor kn-keyword=neurotrophic factor en-keyword=antioxidative molecule kn-keyword=antioxidative molecule END start-ver=1.4 cd-journal=joma no-vol=297 cd-vols= no-issue= article-no= start-page=101071 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210930 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A structural model for (GlcNAc)2 translocation via a periplasmic chitooligosaccharide-binding protein from marine Vibrio bacteria en-subtitle= kn-subtitle= en-abstract= kn-abstract=VhCBP is a periplasmic chitooligosaccharide-binding protein mainly responsible for translocation of the chitooligosaccharide (GlcNAc)2 across the double membranes of marine bacteria. However, structural and thermodynamic understanding of the sugar-binding/-release processes of VhCBP is relatively less. VhCBP displayed the greatest affinity toward (GlcNAc)2, with lower affinity for longer-chain chitooligosaccharides [(GlcNAc)3?4]. (GlcNAc)4 partially occupied the closed sugar-binding groove, with two reducing-end GlcNAc units extending beyond the sugar-binding groove and barely characterized by weak electron density. Mutation of three conserved residues (Trp363, Asp365, and Trp513) to Ala resulted in drastic decreases in the binding affinity toward the preferred substrate (GlcNAc)2, indicating their significant contributions to sugar binding. The structure of the W513A?(GlcNAc)2 complex in a ‘half-open’ conformation unveiled the intermediary step of the (GlcNAc)2 translocation from the soluble CBP in the periplasm to the inner membrane?transporting components. Isothermal calorimetry data suggested that VhCBP adopts the high-affinity conformation to bind (GlcNAc)2, while its low-affinity conformation facilitated sugar release. Thus, chitooligosaccharide translocation, conferred by periplasmic VhCBP, is a crucial step in the chitin catabolic pathway, allowing Vibrio bacteria to thrive in oceans where chitin is their major source of nutrients. en-copyright= kn-copyright= en-aut-name=KitaokuYoshihito en-aut-sei=Kitaoku en-aut-mei=Yoshihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukamizoTamo en-aut-sei=Fukamizo en-aut-mei=Tamo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KumsaoadSawitree en-aut-sei=Kumsaoad en-aut-mei=Sawitree kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UbonbalPrakayfun en-aut-sei=Ubonbal en-aut-mei=Prakayfun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RobinsonRobert C. en-aut-sei=Robinson en-aut-mei=Robert C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugintaWipa en-aut-sei=Suginta en-aut-mei=Wipa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=School of Biomolecular Science and Engineering (BSE), Vidyasirimedhi Institute of Science and Technology (VISTEC) kn-affil= affil-num=2 en-affil=School of Biomolecular Science and Engineering (BSE), Vidyasirimedhi Institute of Science and Technology (VISTEC) kn-affil= affil-num=3 en-affil=School of Biomolecular Science and Engineering (BSE), Vidyasirimedhi Institute of Science and Technology (VISTEC) kn-affil= affil-num=4 en-affil=School of Biomolecular Science and Engineering (BSE), Vidyasirimedhi Institute of Science and Technology (VISTEC) kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=6 en-affil=School of Biomolecular Science and Engineering (BSE), Vidyasirimedhi Institute of Science and Technology (VISTEC) kn-affil= END start-ver=1.4 cd-journal=joma no-vol=109 cd-vols= no-issue=11 article-no= start-page=3916 end-page=3928 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021916 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The eco‐evolutionary dynamics of prior selfing rates promote coexistence without niche partitioning under conditions of reproductive interference en-subtitle= kn-subtitle= en-abstract= kn-abstract=1. Pollinator-mediated reproductive interference can occur when two or more plant species share the same pollinators. Recent studies have suggested that prior autonomous selfing mitigates reproductive interference, potentially facilitating coexistence even in the absence of pollination niche partitioning (i.e. the pre-emptive selfing hypothesis). However, whether the evolution of prior selfing promotes coexistence, in the context of the eco-evolutionary dynamics of population size, selfing rates and inbreeding depression, remains poorly understood.
2. We constructed an individual-based model to examine the conditions under which the evolution of prior selfing promotes coexistence in the context of mutual reproductive interference. In the model, two plant species compete by way of mutual reproductive interference, and both have the potential to evolve the capacity for prior autonomous selfing. We expected that purging of deleterious mutations might result in evolutionary rescue, assuming that the strength of inbreeding depression declines as the population selfing rate increases; this would enable inferior competitors to maintain population density through the evolution of prior selfing.
3. Our simulation demonstrated that evolution of prior selfing may promote coexistence, whereas reproductive interference in the absence of such evolution results in competitive exclusion. We found that lower pollinator availability is likely to favour rapid evolutionary shifts to higher prior selfing rates, thereby neutralising the negative effects of reproductive interference in both species. When the strength of inbreeding depression decreased with an increase in the population-level selfing rate, moderate pollinator availability resulted in long-term coexistence in which relative abundance-dependent selection on the prior selfing rate served to intermittently maintain the population density of the inferior competitor.
4. Synthesis. We demonstrate that the evolution of prior selfing may increase population growth rates of inferior competitors and may consequently promote long-term coexistence via an evolutionary rescue. This constitutes a novel mechanism explaining the co-evolutionary coexistence of closely related plant species without niche partitioning, and is consistent with recent studies reporting that closely related species with mixed mating systems can co-occur sympatrically, even under conditions of mutual reproductive interference. en-copyright= kn-copyright= en-aut-name=KatsuharaKoki en-aut-sei=Katsuhara en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TachikiYuuya en-aut-sei=Tachiki en-aut-mei=Yuuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IritaniRyosuke en-aut-sei=Iritani en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UshimaruAtushi en-aut-sei=Ushimaru en-aut-mei=Atushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Human Development and Environment, Kobe University Kobe kn-affil= affil-num=2 en-affil=Department of Biological Sciences Tokyo Metropolitan University Tokyo Japan kn-affil= affil-num=3 en-affil=Interdisciplinary Theoretical and Mathematical Sciences Program (iTHEMS) RIKEN Wako Saitama Japan kn-affil= affil-num=4 en-affil=Graduate School of Human Development and Environment Kobe University Kobe Japan kn-affil= en-keyword=Co-evolution kn-keyword=Co-evolution en-keyword=evolutionary rescue kn-keyword=evolutionary rescue en-keyword=inbreeding depression kn-keyword=inbreeding depression en-keyword=individual-based model kn-keyword=individual-based model en-keyword=mixed mating kn-keyword=mixed mating en-keyword=pollinator-mediated competition kn-keyword=pollinator-mediated competition en-keyword=reproductive ecology kn-keyword=reproductive ecology en-keyword=selfing syndrome kn-keyword=selfing syndrome END