2024/02/02 更新

写真a

ホソヤ オサム
細谷 修
HOSOYA Osamu
所属
医歯薬学域 助教
職名
助教
外部リンク

学位

  • 博士(理学) ( 新潟大学 )

研究キーワード

  • 細胞生物学

  • Cell Biology

研究分野

  • ライフサイエンス / 細胞生物学

  • ライフサイエンス / 神経科学一般

学歴

  • 新潟大学   Graduate School, Division of Natural Science  

    - 1998年

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  • 新潟大学    

    - 1998年

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    国名: 日本国

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  • 新潟大学   Faculty of Science   Department of Biology

    - 1993年

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    国名: 日本国

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  • 新潟大学   Faculty of Science  

    - 1993年

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経歴

  • 岡山大学   医学部 (解剖学第三講座)   助手

    1998年4月 - 2005年3月

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  • 岡山大学大学院   医歯薬学総合研究科 生体制御科学専攻   助教

    2005年 - 現在

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  • - Assistant Professor,Dept. Neurogenomics, Grad. Sch. Med. Dent. Pharm. Sci., Okayama Univ.,Biophysiological Sciences,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2005年

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  • 岡山大学   医学部   助手

    1998年4月 - 2005年3月

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    国名:日本国

所属学協会

 

論文

  • Candidate Genes in Testing Strategies for Linkage Analysis and Bioinformatic Sorting of Whole Genome Sequencing Data in Three Small Japanese Families with Idiopathic Superior Oblique Muscle Palsy 査読

    Toshihiko Matsuo, Chaomulige, Mary Miyaji, Osamu Hosoya, Akira Saito, Kazuyuki Nakazono

    International Journal of Molecular Sciences   23 ( 15 )   8626 - 8626   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Idiopathic superior oblique muscle palsy is a major type of paralytic, non-comitant strabismus and presents vertical and cyclo-torsional deviation of one eye against the other eye, with a large vertical fusion range and abnormal head posture such as head tilt. Genetic background is considered to play a role in its development, as patients with idiopathic superior oblique muscle palsy have varying degrees of muscle hypoplasia and, rarely, the complete absence of the muscle, that is, aplasia. In this study, whole genome sequencing was performed, and single nucleotide variations and short insertions/deletions (SNVs/InDels) were annotated in two patients each in three small families (six patients in total) with idiopathic superior oblique muscle palsy, in addition to three normal individuals in one family. At first, linkage analysis was carried out in the three families and SNVs/InDels in chromosomal loci with negative LOD scores were excluded. Next, SNVs/InDels shared by the six patients, but not by the three normal individuals, were chosen. SNVs/InDels were further narrowed down by choosing low-frequency (<1%) or non-registered SNVs/InDels in four databases for the Japanese population, and then by choosing SNVs/InDels with functional influence, leading to one candidate gene, SSTR5-AS1 in chromosome 16. The six patients were heterozygous for 13-nucleotide deletion in SSTR5-AS1, except for one homozygous patient, while the three normal individuals were wild type. Targeted polymerase chain reaction (PCR) and direct sequencing of PCR products confirmed the 13-nucleotide deletion in SSTR5-AS1. In the face of newly-registered SSTR5-AS1 13-nucleotide deletion at a higher frequency in a latest released database for the Japanese population, the skipping of low-frequency and non-registration sorting still resulted in only 13 candidate genes including SSTR5-AS1 as common variants. The skipping of linkage analysis also led to the same set of 13 candidate genes. Different testing strategies that consisted of linkage analysis and simple unintentional bioinformatics could reach candidate genes in three small families with idiopathic superior oblique muscle palsy.

    DOI: 10.3390/ijms23158626

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  • Effect of NK-5962 on Gene Expression Profiling of Retina in a Rat Model of Retinitis Pigmentosa 査読

    Shihui Liu, Mary Miyaji, Osamu Hosoya, Toshihiko Matsuo

    International Journal of Molecular Sciences   22 ( 24 )   13276 - 13276   2021年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Purpose: NK-5962 is a key component of photoelectric dye-coupled polyethylene film, designated Okayama University type-retinal prosthesis (OUReP™). Previously, we found that NK-5962 solution could reduce the number of apoptotic photoreceptors in the eyes of the Royal College of Surgeons (RCS) rats by intravitreal injection under a 12 h light/dark cycle. This study aimed to explore possible molecular mechanisms underlying the anti-apoptotic effect of NK-5962 in the retina of RCS rats. Methods: RCS rats received intravitreal injections of NK-5962 solution in the left eye at the age of 3 and 4 weeks, before the age of 5 weeks when the speed in the apoptotic degeneration of photoreceptors reaches its peak. The vehicle-treated right eyes served as controls. All rats were housed under a 12 h light/dark cycle, and the retinas were dissected out at the age of 5 weeks for RNA sequence (RNA-seq) analysis. For the functional annotation of differentially expressed genes (DEGs), the Metascape and DAVID databases were used. Results: In total, 55 up-regulated DEGs, and one down-regulated gene (LYVE1) were found to be common among samples treated with NK-5962. These DEGs were analyzed using Gene Ontology (GO) term enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analyses. We focused on the up-regulated DEGs that were enriched in extracellular matrix organization, extracellular exosome, and PI3K–Akt signaling pathways. These terms and pathways may relate to mechanisms to protect photoreceptor cells. Moreover, our analyses suggest that SERPINF1, which encodes pigment epithelium-derived factor (PEDF), is one of the key regulatory genes involved in the anti-apoptotic effect of NK-5962 in RCS rat retinas. Conclusions: Our findings suggest that photoelectric dye NK-5962 may delay apoptotic death of photoreceptor cells in RCS rats by up-regulating genes related to extracellular matrix organization, extracellular exosome, and PI3K–Akt signaling pathways. Overall, our RNA-seq and bioinformatics analyses provide insights in the transcriptome responses in the dystrophic RCS rat retinas that were induced by NK-5962 intravitreal injection and offer potential target genes for developing new therapeutic strategies for patients with retinitis pigmentosa.

    DOI: 10.3390/ijms222413276

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  • A modified Tet-ON system minimizing leaky expression for cell-type specific gene induction in medaka fish.

    Osamu Hosoya, Myung Chung, Satoshi Ansai, Hideaki Takeuchi, Mary Miyaji

    Development, growth & differentiation   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The Tet-ON system is an important molecular tool for temporally and spatially-controlled inducible gene expression. Here, we developed a Tet-ON system to induce transgene expression specifically in the rod photoreceptors of medaka fish. Our modified reverse tetracycline-controlled transcriptional transactivator (rtTAm) with 5 amino acid substitutions dramatically improved the leakiness of the transgene in medaka fish. We generated a transgenic line carrying a self-reporting vector with the rtTAm gene driven by the Xenopus rhodopsin promoter and a tetracycline response element (TRE) followed by the green fluorescent protein (GFP) gene. We demonstrated that GFP fluorescence was restricted to the rod photoreceptors in the presence of doxycycline in larval fish (9 days post-fertilization). The GFP fluorescence intensity was enhanced with longer durations of doxycycline treatment up to 72 h and in a dose-dependent manner (5-45 μg/ml). These findings demonstrate that the Tet-ON system using rtTAm allows for spatiotemporal control of transgene expression, at least in the rod photoreceptors, in medaka fish.

    DOI: 10.1111/dgd.12743

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  • The Effect of Cyanine Dye NK-4 on Photoreceptor Degeneration in a Rat Model of Early-Stage Retinitis Pigmentosa. 国際誌

    Shihui Liu, Toshihiko Matsuo, Mary Miyaji, Osamu Hosoya

    Pharmaceuticals (Basel, Switzerland)   14 ( 7 )   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The present study aimed to evaluate the effects of NK-4 on the apoptosis of photoreceptors in a rat model of retinitis pigmentosa and explore the mechanism underlying anti-apoptosis activity. The Royal College of Surgeons (RCS) rats received an intravitreous injection of NK-4 solution in the left eye and vehicle control in the right eye. Apoptosis was detected by TUNEL method in frozen sections of the eyes. The retinal tissues of the rats were dissected for RNA-seq analysis. Functional and pathway enrichment analyses of differentially expressed genes (DEGs) were performed by using Metascape and DAVID software. The expression levels of DEGs were confirmed by real-time quantitative PCR (RT-qPCR). The number of apoptotic cells decreased in the outer nuclear layer (ONL) and the thickness of the ONL was significantly thicker in the retina of NK-4-injected eyes, compared with control eyes. Five DEGs were identified by RNA-seq analysis, and Hmox1, Mt1, Atf5, Slc7a11, and Bdh2 were confirmed to be up-regulated by RT-qPCR. Functional and pathway enrichment analysis of the up-regulated genes showed that anti-apoptosis effects of NK-4 in the retina of RCS rats may be related to the pathways of metal ion homeostasis, negative regulation of neuron death, response to toxic substance, and pigment metabolic process. We found a potential mechanism of NK-4, providing a new viewpoint for the development of more therapeutic uses of NK-4 in the future.

    DOI: 10.3390/ph14070694

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  • Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to induce chromatin opening

    Mary Miyaji, Ryohei Furuta, Osamu Hosoya, Kuniaki Sano, Norikazu Hara, Ryozo Kuwano, Jiyoung Kang, Masaru Tateno, Kimiko M. Tsutsui, Ken Tsutsui

    Scientific Reports   10 ( 1 )   2020年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    <title>Abstract</title>
    Type II DNA topoisomerases (topo II) flip the spatial positions of two DNA duplexes, called G- and T- segments, by a cleavage-passage-resealing mechanism. In living cells, these DNA segments can be derived from distant sites on the same chromosome. Due to lack of proper methodology, however, no direct evidence has been described so far. The beta isoform of topo II (topo IIβ) is essential for transcriptional regulation of genes expressed in the final stage of neuronal differentiation. Here we devise a genome-wide mapping technique (eTIP-seq) for topo IIβ target sites that can measure the genomic distance between G- and T-segments. It revealed that the enzyme operates in two distinctive modes, termed proximal strand passage (PSP) and distal strand passage (DSP). PSP sites are concentrated around transcription start sites, whereas DSP sites are heavily clustered in small number of hotspots. While PSP represent the conventional topo II targets that remove local torsional stresses, DSP sites have not been described previously. Most remarkably, DSP is driven by the pairing between homologous sequences or repeats located in a large distance. A model-building approach suggested that topo IIβ acts on crossovers to unknot the intertwined DSP sites, leading to chromatin decondensation.

    DOI: 10.1038/s41598-020-75004-w

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    その他リンク: http://www.nature.com/articles/s41598-020-75004-w

  • Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to modulate chromatin structure and gene expression

    Mary Miyaji, Ryohei Furuta, Osamu Hosoya, Kuniaki Sano, Norikazu Hara, Ryozo Kuwano, Jiyoung Kang, Masaru Tateno, Kimiko M. Tsutsui, Ken Tsutsui

    BioRxiv (Cold Harbor Laboratory, CSHL)   2018年12月

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    記述言語:英語   出版者・発行元:Cold Spring Harbor Laboratory  

    <title>Abstract</title><sec><title>Background</title>Type II DNA topoisomerases (topo II) flip the spatial positions of two DNA duplexes, called G- and T-segments, by a cleavage-passage-resealing mechanism. In living cells, these DNA segments can be placed far from each other on the same chromosome. However, no direct evidence for this to occur has been described so far due to lack of proper methodology.

    </sec><sec><title>Results</title>The beta isoform of topo II (topo IIβ) is essential for transcriptional regulation of genes expressed in the final stage of neuronal differentiation. To elucidate the enzyme’s role in the process, here we devise a genome-wide mapping technique for topo IIβ target sites that can measure the genomic distance between G- and T-segments. It became clear that the enzyme operates in two distinctive modes, termed proximal strand passage (PSP) and distal strand passage (DSP). PSP sites are concentrated around transcription start sites, whereas DSP sites are heavily clustered in small number of hotspots. While PSP represent the conventional topo II targets that remove local torsional stresses, DSP sites have not been described previously. Most remarkably, DSP is driven by the pairing between homologous sequences or repeats located in a large distance. A model-building approach suggested that the DSP sites are intertwined or knotted and topo IIβ is engaged in unknotting reaction that leads to chromatin decondensation and gene regulation.

    </sec><sec><title>Conclusions</title>When combined with categorized gene expression analysis, the model-based prediction of DSP sites reveals that DSP is one of the key factors for topo IIβ-dependency of neuronal gene regulation.

    </sec>

    DOI: 10.1101/484956

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  • Visual evoked potential in RCS rats with Okayama University-type retinal prosthesis (OUReP™) implantation. 査読

    Alamusi, Matsuo T, Hosoya O, Uchida T

    Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs   20 ( 2 )   158 - 165   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s10047-016-0943-4

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  • Photoelectric Dye Used for Okayama University-Type Retinal Prosthesis Reduces the Apoptosis of Photoreceptor Cells 査読

    Shihui Liu, Toshihiko Matsuo, Osamu Hosoya, Tetsuya Uchida

    JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS   33 ( 3 )   149 - 160   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MARY ANN LIEBERT, INC  

    Purpose: Our previous study demonstrated that photoelectric dye-coupled polyethylene film (Okayama University-type retinal prosthesis), which was implanted in subretinal space of the eyes of Royal College of Surgeons (RCS) rats, prevented retinal neurons from apoptotic death. In this study, we aimed to examine whether photoelectric dye itself would protect retinal neurons from apoptosis in RCS rats.
    Methods: RCS rats received intravitreous injection of different concentrations of the dye in the left eye and housed under a 12-h light-dark cycle. Saline injection in the right eye served as control. In addition, RCS rats with dye injection were kept in 24-h daily dark condition. Sections were processed for terminal deoxynucleotidyl transferase-mediated fluorescein-conjugated-dUTP nick-end-labeling (TUNEL) assay and immunohistochemical staining of glial fibrillary acidic protein (GFAP) and protein kinase C alpha (PKC alpha).
    Results: The number of TUNEL-positive cells significantly decreased in the retina of dye-injected eyes compared with those in saline-injected eyes (P = 0.0001, 2-factor analysis of variance [ANOVA]), under 12-h light-dark cycle. Significant decrease of TUNEL-positive cells was noted in the retina of rats with dye injection compared with those with saline injection, kept under 24-h dark condition (P = 0.0001, 2-factor ANOVA). Immunoreactive area for GFAP decreased significantly in the retina of dye-injected eyes compared with that in controls (P = 0.0001, 2-factor ANOVA), whereas immunoreactive area for PKCa increased significantly in the retina of dye-injected eyes compared with that in controls (P = 0.01, 2-factor ANOVA).
    Conclusions: Photoelectric dye inhibits apoptotic death of photoreceptor cells in RCS rats and downregulates GFAP expression in retinal Muller cells. Photoelectric dye may be a candidate agent for neuroprotection in retinitis pigmentosa and other retinal diseases.

    DOI: 10.1089/jop.016.0093

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  • The CENP-O complex requirement varies among different cell types. 査読

    Kagawa N, Hori T, Hoki Y, Hosoya O, Tsutsui K, Saga Y, Sado T, Fukagawa T

    Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology   22 ( 3 )   293 - 303   2014年9月

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    出版者・発行元:3  

    DOI: 10.1007/s10577-014-9404-1

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  • Sertoli cellで発現するシナプスタンパク質Amphiphysin Iと精子形成

    渡部 昌実, 永井 敦, 井口 裕樹, 公文 裕巳, 筒井 公子, 細谷 修, 徳永 叡, 筒井 研

    日本泌尿器科学会雑誌   91 ( 3 )   372 - 372   2000年

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    記述言語:日本語   出版者・発行元:一般社団法人 日本泌尿器科学会  

    DOI: 10.5980/jpnjurol.91.372_1

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▼全件表示

MISC

  • 改良型Tet-ONシステムを用いたメダカ網膜桿体特異的な遺伝子発現誘導

    細谷 修, Chung Myung, 安齋 賢, 竹内 秀明, 宮地 まり

    第44回 日本分子生物学会年会抄録   2021年12月

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    担当区分:筆頭著者   記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)  

  • メダカDNAトポイソメラーゼIIβによる神経系の遺伝子発現制御

    宮地 まり, 河野 真二, 細谷 修, 竹内 秀明, 筒井 公子, 筒井 研

    第44回 日本分子生物学会年会抄録   2021年12月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)  

  • A new knock-out mouse model (MGST2 gene knock-out) for strabismus

    Chaomulige, Toshihiko Matsuo, Shihui Liu, Mary Miyaji, Osamu Hosoya, Izuho Hatada, Takuro Horii

    ARVO 2020 Annual Meeting Abstract   61 ( 7 )   2020年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Prevention of apoptotic photoreceptor cell death by a Cryptocyanine drug (NK-4) during inherited retinal degeneration in RCS rats

    Shihui Liu, Toshihiko Matsuo, Mary Miyaji, Osamu Hosoya

    ARVO 2020 Annual Meeting Abstract   61 ( 7 )   2020年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • トポイソメラーゼIIβは遠隔ゲノム部位の相同配列間に働いてクロマチンを脱凝縮し神経関連遺伝子の発現に関与する

    第42回日本分子生物学会年会抄録   2019年12月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)  

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  • トポイソメラーゼIIβの遠隔ゲノム部位間での働きを解析するeTIP-seq法の検証

    Ryohei Furuta, Mary Miyaji, Osamu Hosoya, Kuniaki Sano, Kimiko M. Tsutsui, Ken Tsutsui

    第42回日本分子生物学会年会抄録   2019年12月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)  

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  • Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to modulate chromatin structure and gene expression 国際誌

    Mary Miyaji, Ryohei Furuta, Osamu Hosoya, Kuniaki Sano, Norikazu Hara, Ryozo Kuwano, Jiyoung Kang, Masaru Tateno, Kimiko M. Tsutsui, Ken Tsutsui

    BioRxiv (Cold Harbor Laboratory, CSHL)   2019年10月

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    記述言語:英語   出版者・発行元:(Cold Harbor Laboratory, CSHL)  

    Type II DNA topoisomerases (topo II) flip the spatial positions of two DNA duplexes, called G- and T-segments, by a cleavage-passage-resealing mechanism. In living cells, these DNA segments can be placed far from each other on the same chromosome. However, no direct evidence for this to occur has been described so far due to lack of proper methodology.
    (Results)The beta isoform of topo II (topo IIβ) is essential for transcriptional regulation of genes expressed in the final stage of neuronal differentiation. To elucidate the enzyme’s role in the process, here we devise a genome-wide mapping technique for topo IIβ target sites that can measure the genomic distance between G- and T-segments. It became clear that the enzyme operates in two distinctive modes, termed proximal strand passage (PSP) and distal strand passage (DSP). PSP sites are concentrated around transcription start sites, whereas DSP sites are heavily clustered in small number of hotspots. While PSP represent the conventional topo II targets that remove local torsional stresses, DSP sites have not been described previously. Most remarkably, DSP is driven by the pairing between homologous sequences or repeats located in a large distance. A model-building approach suggested that the DSP sites are intertwined or knotted and topo IIβ is engaged in unknotting reaction that leads to chromatin decondensation and gene regulation.
    (Conclusions) When combined with categorized gene expression analysis, the model-based prediction of DSP sites reveals that DSP is one of the key factors for topo IIβ-dependency of neuronal gene regulation.

    DOI: 10.1101/484956

  • Key pathways and genes influenced by a drug, NK-4 (Lumin), in Royal College Surgeon Rats

    Shihui Liu, Toshihiko Matsuo, Mary Miyaji, Osamu Hosoya

    ARVO 2019 Annual Meeting Abstract   60 ( 9 )   2019年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • トポイソメラーゼIIβは神経細胞終末分化において遠隔ゲノム部位の相同配列間に働きクロマチン脱凝縮を誘導する

    宮地まり, 古田良平, 細谷 修, 佐野訓明, 筒井公子, 筒井 研

    第36回染色体ワークショップ 第17回核ダイナミクス研究会抄録   2019年1月

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    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)  

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  • Key pathways and genes influenced by a drug, NK-4 (Lumin), in human neurons and Royal College Surgeon Rats

    Shihui Liu, Toshihiko Matsuo, Mary Miyaji, Osamu Hosoya

    ARVO 2018 Annual Meeting Abstract   59 ( 9 )   2018年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • NK4 dye reduces the apoptosis of photoreceptor cells.

    Shihui Liu, Toshihiko Matsuo, Osamu Hosoya

    ARVO 2017 Annual Meeting Abstract   58 ( 8 )   2017年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Apoptosis reduction by a photoelectric dye used for Okayama University-type retinal prosthesis (OURePTM).

    Shihui Liu, Toshihiko Matsuo, Osamu Hosoya

    ARVO 2016 Annual Meeting Abstract   2016年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

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  • Vision maintenance and retinal apoptosis reduction in RCS rats with Okayama University-type retinal prosthesis (OUReP (TM)) implantation

    Alamusi, Toshihiko Matsuo, Osamu Hosoya, Kimiko M. Tsutsui, Tetsuya Uchida

    JOURNAL OF ARTIFICIAL ORGANS   18 ( 3 )   264 - 271   2015年9月

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    記述言語:英語   出版者・発行元:SPRINGER JAPAN KK  

    Photoelectric dye-coupled polyethylene film, designated Okayama University-type retinal prosthesis or OUReP (TM), generates light-evoked surface electric potentials and stimulates neurons. In this study, the vision was assessed by behavior tests in aged hereditary retinal dystrophic RCS rats with OUReP (TM), retinal apoptosis and electroretinographic responses were measured in dystrophic eyes with OUReP (TM). The dye-coupled films, or plain films as a control, were implanted in subretinal space of RCS rats. On behavior tests, RCS rats with dye-coupled films, implanted at the old age of 14 weeks, showed the larger number of head-turning, consistent with clockwise and anticlockwise rotation of a surrounding black-and-white-striped drum, compared with rats with plain films, under the dim (50 lux) and bright (150 lux) conditions in the observation period until the age of 22 weeks (n = 5, P &lt; 0.05, repeated-measure ANOVA). The number of apoptotic cells in retinal sections at the site of dye-coupled film implantation was significantly smaller, compared with the other retinal sites, neighboring the film, or opposite to the film, 5 months after film implantation at the age of 6 weeks (P = 0.0021, Friedman test). The dystrophic eyes of RCS rats with dye-coupled films showed positive responses to maximal light stimulus at a significantly higher rate, compared with the eyes with no treatment (P &lt; 0.05, Chi-square test). Electroretinograms in normal eyes of Wistar rats with dye-coupled or plain films showed significantly decreased amplitudes (n = 14, P &lt; 0.05, repeated-measure ANOVA). In conclusions, vision was maintained in RCS rats with dye-coupled films implanted at the old age. The dystrophic eyes with dye-coupled films showed electroretinographic responses. Five-month film implantation caused no additional retinal changes.

    DOI: 10.1007/s10047-015-0825-1

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  • 精神・神経疾患に関連する長大遺伝子の発現制御機構

    宮地まり, 佐野訓明, 古田良平, 細谷修, 筒井公子, 筒井研

    月刊細胞   47 ( 5 )   25 - 28   2015年

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  • 人工臓器「第52回日本人工臓器学会大会 論文賞(広領域)受賞レポート」

    阿拉木斯, 松尾俊彦, 細谷修, 筒井公子, 内田哲也

    人工臓器   44 ( 1 )   16 - 17   2015年

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  • Vision recovery and retinal apoptosis reduction in RCS rats with Okayama University-type retinal prosthesis

    Bai Alamusi, Toshihiko Matsuo, Osamu Hosoya, Kimiko M. Tsutsui, Tetsuya Uchida

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   55 ( 13 )   2014年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

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  • Nuclear dynamics of topoisomerase IIβ reflects its catalytic activity that is regulated by binding of RNA to the C-terminal domain

    A. Onoda, O. Hosoya, K. Sano, K. Kiyama, H. Kimura, S. Kawano, R. Furuta, M. Miyaji, K. Tsutusi, K.M. Tsutsui

    Nucleic Acids Research   42 ( 14 )   9005 - 9020   2014年

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  • 人工臓器「第51回日本人工臓器学会大会 Tominaga Award 2012受賞レポート」

    阿拉木斯, 松尾俊彦, 細谷修, 筒井公子, 内田哲也

    人工臓器   43 ( 1 )   31 - 32   2014年

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  • Behavior tests and immunohistochemical retinal response analyses in RSC rats with subretinal implantation of Okayama-University-type retinal prosthesis (共著)

    Alamusi, Matsuo T, Hosoya O, Tsutsui KM, Uchida T

    Journal of Artificial Organs   16 ( 3 )   343 - 351   2013年9月

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  • Nuclear protein LEDGF/p75 recognizes supercoiled DNA by a novel DNA-binding domain

    Kimiko M. Tsutsui, Kuniaki Sano, Osamu Hosoya, Tadashi Miyamoto, Ken Tsutsui

    NUCLEIC ACIDS RESEARCH   39 ( 12 )   5067 - 5081   2011年7月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS  

    Lens epithelium-derived growth factor (LEDGF) or p75 is a co-activator of general transcription and also involved in insertion of human immunodeficiency virus type I (HIV-1) cDNA into host cell genome, which occurs preferentially to active transcription units. These phenomena may share an underlying molecular mechanism in common. We report here that LEDGF/p75 binds negatively supercoiled DNA selectively over unconstrained DNA. We identified a novel DNA-binding domain in the protein and termed it &apos;supercoiled DNA-recognition domain&apos; (SRD). Recombinant protein fragments containing SRD showed a preferential binding to supercoiled DNA in vitro. SRD harbors a characteristic cluster of lysine and glutamic/aspartic acid residues. A polypeptide mimicking the cluster (K(9)E(9)K(9)) also showed this specificity, suggesting that the cluster is an essential element for the supercoil recognition. eGFP-tagged LEDGF/p75 expressed in the nucleus distributed partially in transcriptionally active regions that were identified by immunostaining of methylated histone H3 (H3K4me3) or incorporation of Br-UTP. This pattern of localization was observed with SRD alone but abolished if the protein lacked SRD. Thus, these results imply that LEDGF/p75 guides its binding partners, including HIV-1 integrase, to the active transcription site through recognition of negative supercoils generated around it.

    DOI: 10.1093/nar/gkr088

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  • Glial reaction to photoelectric dye-based retinal prostheses implanted in the subretinal space of rats

    Takayuki Tamaki, Toshihiko Matsuo, Osamu Hosoya, Kimiko M. Tsutsui, Tetsuya Uchida, Kazuo Okamoto, Akihito Uji, Hiroshi Ohtsuki

    JOURNAL OF ARTIFICIAL ORGANS   11 ( 1 )   38 - 44   2008年4月

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    記述言語:英語   出版者・発行元:SPRINGER TOKYO  

    We have designed a new type of retinal prosthesis using polyethylene films coupled with photoelectric dye molecules that absorb light and convert photon energy to electric potentials. An extruded-blown film of high-density polyethylene was used as the original polyethylene film. Recrystallized film was made by recrystallization from the melting of the original polyethylene film. A photoelectric dye,2-[2-[4-(dibutylamino)phenyl]ethenyl]-3-carboxymethylbenzothiazolium bromide, was coupled to the two types of polyethylene films through amide linkages. Samples of the original dye-coupled film, the dye-coupled recrystallized film, and the dye-uncoupled plain film were implanted in the subretinal space of normal adult rats. Frozen sections were cut from the eyes enucleated at 1 week or 1 month and were either stained with hematoxylin and eosin, stained immunohistochemically for glial fibrillary acidic protein (GFAP), or processed for in situ apoptosis detection. The results revealed that retinal tissue damage was negligible with no inflammatory cells and few apoptotic cells. GFAP was significantly up-regulated in retinal sites with the implantation of all types of polyethylene films at 1 week, compared with the adjacent retinal sites (P &lt; 0.005, analysis of variance). The GFAP up-regulation was also present at 1 month for the plain film and dye-coupled recrystallized film (P &lt; 0.05). Glial cell encirclement around the films increased significantly between 1 week and 1 month (P = 0.023, two-factor analysis of variance) but was not significantly different among the three types of polyethylene films (P = 0.4531). These results showed evidence of glial reactions to the photoelectric dye-coupled polyethylene films implanted into the subretinal space of rat eyes and also proved their basic biological safety.

    DOI: 10.1007/s10047-007-0398-8

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  • Amphiphysin Ir participates in receptor-mediated endocytosis in ARPE-19

    Osamu Hosoya, Ken Tsutsui, Kimiko Tsutsui

    NEUROSCIENCE RESEARCH   58   S95 - S95   2007年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

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  • Expression dynamics and functional implications of DNA topoisomerase II beta in the brain

    Kimiko M. Tsutsui, Kuniaki Sano, Osamu Hosoya, Ken Tsutsui

    ANATOMICAL SCIENCE INTERNATIONAL   81 ( 3 )   156 - 163   2006年9月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:BLACKWELL PUBLISHING  

    Mammalian DNA topoisomerase II beta is a type 11 DNA topoisomerase that catalyses topological transformations of genomic DNA by the transport of one DNA double helix through another. The II beta enzyme is highly expressed in cells that have undergone the final cell division and committed to differentiate into neuronal cells. The Ilp enzyme in the differentiating neuronal cells is located in the nucleoplasm and is actively engaged in its catalytic reaction in vivo. When enzyme action is interfered with a specific inhibitor in vitro, transcriptional induction of a subset of genes fails to occur during neuronal differentiation. Detailed analyses of developing rat cerebellum and the cerebrum of mice with disrupted Ilp genes have revealed that DNA topoisomerase II beta is necessary for the developmentally regulated expression of certain genes in cells committed to a neuronal fate after the final division. Herein, we review a dynamic aspect of DNA topoisomerase Ilp in the brain with special emphasis on developing cerebellar neurons.

    DOI: 10.1111/j.1447-073x.2006.00146.x

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  • Expression dynamics and functional implications of DNA topoisomeraseⅡβ in the brain

    Tsutsui K M, Sano K, Hosoya O, Tsusui K

    Anatomical Science International   81 ( 3 )   156 - 163   2006年9月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等  

    DOI: 10.1111/j.1447-073x.2006.00146.x

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  • Subcellular localization of amphiphysin Ir in AREP-19 cells

    Osamu Hosoya, Ken Tsutsui, Kimiko Tsutsui

    NEUROSCIENCE RESEARCH   55   S147 - S147   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

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  • Localized expression of amphiphysin Ir, a retina-specific variant of amphiphysin I, in the ribbon synapse and its functional implication

    O Hosoya, K Tsutsui, K Tsutsui

    EUROPEAN JOURNAL OF NEUROSCIENCE   19 ( 8 )   2179 - 2187   2004年4月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    In the vertebrate retina, presynaptic terminals of photoreceptors and bipolar cells form ribbon synapses and release neurotransmitter continuously. Endocytic machinery in the ribbon synapse is likely to differ from that in conventional synapses because of the much higher rate of synaptic vesicle recycling. However, protein components of the ribbon synapse identified so far are quite similar to those of the conventional synapses. Recently we identified amphiphysin I splice variants, termed amphiphysin Ir, that are transcribed specifically in retina from the authentic amphiphysin I gene [Y Terada et al. (2002) FEBS Lett., 519, 185-190]. Amphiphysin I is a nerve terminal-enriched protein, and involved in synaptic vesicle endocytosis as heterodimer with amphiphysin II, an isoform of amphiphysin I. We report here that the retina-specific amphiphysin Ir is expressed exclusively in the ribbon synapse and not in conventional synapses. This is the first endocytosis-related, ribbon synapse-specific protein identified in the retina. By immunoprecipitation and double-immunolabelling, amphiphysin Ir was shown to be associated not only with amphiphysin 11, but also with dynamin, clathrin and alpha-adaptin that are involved in synaptic vesicle recycling. The results suggest that endocytosis of the synaptic vesicle membrane in retinal ribbon synapses proceeds through a pathway similar to the one that is used in conventional synapses, although amphiphysin Ir is substituted for amphiphysin I. Amphiphysin Ir may play an essential role in the avid endocytic activity of ribbon synapses by associating with yet unknown protein partner(s) through its large insertional domain, which is absent from the conventional amphiphysin I.

    DOI: 10.1111/j.1460-9568.2004.03340.x

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  • Elucidating the role of amphiphysin Ir in retinal ribbon synapses

    Osamu Hosoya, Ken Tsutsui, Kimiko Tsutsui

    Neuroscience research   2003年

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  • Localization of dynamin 2 in rat seminiferous tubules during the spermatogenic cycle

    H Iguchi, M Watanabe, A Kamitani, A Nagai, O Hosoya, K Tsutsui, H Kumon

    ACTA MEDICA OKAYAMA   56 ( 4 )   205 - 209   2002年8月

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    記述言語:英語   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Dynamin is a protein essential to endocytosis. Dynamin 2, a dynamin isoform, is expressed most intensely in testicular tissue; however, precise localization has never been studied. Therefore, we investigated the expression of dynamin 2 in rat testicular tissue using immunohistochemical methods, and discuss here the physiological function of this protein. Testicular tissues were obtained from Wistar rats at 10, 21 and 63 days of age. Immunohistochemistrical examination and Western blot analysis were conducted using dynamin 2 specific antibody. Western blot analysis showed that expression in 21- and 63-day-old rats was more intense than that in 10-day-old rats. Dynamin 2 expression was observed using immunohistochemical method in the seminiferous tubules of all rats. In the 63-day-old rats, the expression was intense, especially in spermatids in the earlier maturation stages and in spermatocytes, and was observed in Sertoli cells. However, in spermatids, the expression gradually declined as spermatids matured to spermatozoa. In the 21-day-old rats, the expression was evident in spermatocytes and Sertoli cells, but that in the 10-day-old rats was weak. Intense expression of dynamin 2 during spermatogenesis suggests that this protein plays an important role in this process.

    DOI: 10.18926/AMO/31681

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  • Novel splice variants of amphiphysin I are expressed in retina

    Y Terada, K Tsutsui, K Sano, O Hosoya, H Ohtsuki, A Tokunaga, K Tsutsui

    FEBS LETTERS   519 ( 1-3 )   185 - 190   2002年5月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Using RT-PCR-based cDNA cloning, we identified novel splice variants of amphiphysin I, termed amph Ir, that are expressed specifically in retina. In comparison with the prototype amphiphysin I, amph Ir contained two novel insertions (inserts A and B) and one deletion. Insert A is only 9 bp in length but appears to be a determinant for the retina-specific expression. In contrast, insert B is a large domain of 1740 bp and two shorter transcripts with 3'-truncated insert B were also expressed. All the insert sequences were present as unidentified exons in the amphiphysin I gene on human chromosome 7. Western blot analysis of various rat tissues with anti-insert B antibody confirmed the presence and tissue specificity of the variant proteins. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

    DOI: 10.1016/S0014-5793(02)02763-1

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  • Localization and functional role of amphiphysin Ir in retinal ribbon synapses.

    Hosoya O, Tsutsui K, Sano K, Tsutsui K

    Neurosci Res Suppl   26/S37   2002年

  • Expression of amphiphysin I in sertoli cells and its implication in spermatogenesis

    M Watanabe, K Tsutsui, O Hosoya, K Tsutsui, H Kumon, A Tokunaga

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   287 ( 3 )   739 - 745   2001年9月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Amphiphysin I is a protein concentrated in nerve terminals and involved in the endocytosis of synaptic vesicle membrane. We show here that amphiphysin I is expressed in the rat testis, localized exclusively in the Sertoli cells. In the postnatal testicular development, expression of amphiphysin I was not evident at birth, but became significant at postnatal day 15 (P15), coinciding with the onset of spermatogenesis. The expression level of amphiphysin I increased 10-fold between P15 and P25 to reach the adult level. In adult testes reversibly damaged by ethane dimethane sulphonate administration, expression of amphiphysin I did not change following the damage, whereas the protein was transiently converted into its phosphorylated form. The increase in levels of phosphorylated amphiphysin I was closely associated with the severe histological damage to germ cells. The present findings suggest that amphiphysin I in Sertoli cells is involved in spermatogenesis, probably through endocytic processes. (C) 2001 Academic Press.

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  • Expression of amphiphysin I in sertoli cells and its implication in spermatogenesis

    M Watanabe, K Tsutsui, O Hosoya, K Tsutsui, H Kumon, A Tokunaga

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   287 ( 3 )   739 - 745   2001年9月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Amphiphysin I is a protein concentrated in nerve terminals and involved in the endocytosis of synaptic vesicle membrane. We show here that amphiphysin I is expressed in the rat testis, localized exclusively in the Sertoli cells. In the postnatal testicular development, expression of amphiphysin I was not evident at birth, but became significant at postnatal day 15 (P15), coinciding with the onset of spermatogenesis. The expression level of amphiphysin I increased 10-fold between P15 and P25 to reach the adult level. In adult testes reversibly damaged by ethane dimethane sulphonate administration, expression of amphiphysin I did not change following the damage, whereas the protein was transiently converted into its phosphorylated form. The increase in levels of phosphorylated amphiphysin I was closely associated with the severe histological damage to germ cells. The present findings suggest that amphiphysin I in Sertoli cells is involved in spermatogenesis, probably through endocytic processes. (C) 2001 Academic Press.

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  • Immunohistochemical analyses of DNA topoisomerase II isoforms in developing rat cerebellum

    K Tsutsui, K Tsutsui, O Hosoya, K Sano, A Tokunaga

    JOURNAL OF COMPARATIVE NEUROLOGY   431 ( 2 )   228 - 239   2001年3月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    In mammalian cells, two isoforms of DNA topoisomerase II (topo II alpha and topo II beta) have been identified. Topo II alpha is essential in mitotic cells, whereas the function of topo II beta remains unclear. In the present study, we investigated the developmental control of topo II isoforms in two different neuronal lineages, cerebellar Purkinje cells and granule cells, by immunohistochemical analysis with isoform-specific monoclonal antibodies. As expected, proliferating cells in the neuroepithelium and in the external germinal layer (EGL) were topo II alpha immunopositive. The migrating as well as differentiating Purkinje cells and granule cells showed an enhanced topo II beta immunoreactivity. The postmitotic granule cells in the post natal EGL showed an abrupt transition of expressed topo II isoforms from II alpha to II beta. The transition was clearly coincident with the completion of final cell division and the initiation of terminal differentiation because no increase of the topo II beta immunoreactivity was observed in the spreading EGL cells that are still in the cell division cycle. The topo II beta signal was detected in both nucleoplasm and nucleolus of differentiating cells. However, the nucleoplas mic signal decreased significantly as the cells reached terminal differentiation. The residual topo II beta in nucleoli was shown to occupy an unique location with respect to other nucleolar proteins, nucleolin and DNA topoisomerase I. Our findings indicate that both Purkinje cells and granule cells express the topo II isoforms in a similar timing during the cerebellar development and also suggest that topo II beta localized in nucleoplasm is the functional entity involved in neuronal differentiation. J. Comp. Neurol. 431:228-239, 2001. (C) 2001 Wiley-Liss, Inc.

    DOI: 10.1002/1096-9861(20010305)431:2<228::AID-CNE1067>3.0.CO;2-M

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  • Immunohistochemical analyses of DNA topoisomerase II isoforms in developing rat cerebellum

    K Tsutsui, K Tsutsui, O Hosoya, K Sano, A Tokunaga

    JOURNAL OF COMPARATIVE NEUROLOGY   431 ( 2 )   228 - 239   2001年3月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    In mammalian cells, two isoforms of DNA topoisomerase II (topo II alpha and topo II beta) have been identified. Topo II alpha is essential in mitotic cells, whereas the function of topo II beta remains unclear. In the present study, we investigated the developmental control of topo II isoforms in two different neuronal lineages, cerebellar Purkinje cells and granule cells, by immunohistochemical analysis with isoform-specific monoclonal antibodies. As expected, proliferating cells in the neuroepithelium and in the external germinal layer (EGL) were topo II alpha immunopositive. The migrating as well as differentiating Purkinje cells and granule cells showed an enhanced topo II beta immunoreactivity. The postmitotic granule cells in the post natal EGL showed an abrupt transition of expressed topo II isoforms from II alpha to II beta. The transition was clearly coincident with the completion of final cell division and the initiation of terminal differentiation because no increase of the topo II beta immunoreactivity was observed in the spreading EGL cells that are still in the cell division cycle. The topo II beta signal was detected in both nucleoplasm and nucleolus of differentiating cells. However, the nucleoplas mic signal decreased significantly as the cells reached terminal differentiation. The residual topo II beta in nucleoli was shown to occupy an unique location with respect to other nucleolar proteins, nucleolin and DNA topoisomerase I. Our findings indicate that both Purkinje cells and granule cells express the topo II isoforms in a similar timing during the cerebellar development and also suggest that topo II beta localized in nucleoplasm is the functional entity involved in neuronal differentiation. J. Comp. Neurol. 431:228-239, 2001. (C) 2001 Wiley-Liss, Inc.

    DOI: 10.1002/1096-9861(20010305)431:2<228::AID-CNE1067>3.0.CO;2-M

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  • Immunocytochemical studies on the cellular origin of ectopic striated muscle fibers in monolayer cultures of rat anterior pituitary cells

    O Hosoya, YG Watanabe

    ZOOLOGICAL SCIENCE   15 ( 2 )   247 - 253   1998年4月

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    記述言語:英語   出版者・発行元:ZOOLOGICAL SOC JAPAN  

    We have previously reported that glia-like folliculo-stellate (FS) cells in the rat anterior pituitary may be involved in heterotopic differentiation of striated muscles which appear during pituitary cell culture. In the present immunocytochemical study, cytological alterations of FS cells in vitro were investigated by using antibodies to marker proteins (i.e., S-100 and vimentin) for FS cells. Expression of skeletal muscle-specific MyoD1 detected by immunocytochemistry, enabled identification of myogenic cells at a stage when they were still unicellular. Elongated myoblasts containing MyoD1-positive nuclei were found as early as the fifth day of monolayer culture of pituitary cells. The double immunostaining technique showed that some of these myoblasts reacted with antiserum to S-100. Although all of the myoblasts were immunoreactive to vimentin, this marker protein was unable to identify FS cells in vitro because rapidly proliferating fibroblasts were also immunoreactive to vimentin. Since the antiserum to S-100 that we used did not react with already differentiated striated muscle fibers, the demonstration of both MyoD1 and S-100-immunoreactive myoblasts in our pituitary cultures suggests that these myogenic cells are derived from FS cells. The present study does not rule out the possibility that fibroblasts, whose origin is presently unknown, are also involved in myogenesis in pituitary cultures.

    DOI: 10.2108/zsj.15.247

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  • Immunocytochemical studies on the cellular origin of ectopic striated muscle fibers in monolayer cultures of rat anterior pituitary cells

    Osamu Hosoya, Yuichi G. Watanabe

    Zoological Science   15 ( 2 )   247 - 253   1998年

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    記述言語:英語   出版者・発行元:Zoological Society of Japan  

    We have previously reported that glia-like folliculo-stellate (FS) cells in the rat anterior pituitary may be involved in heterotopic differentiation of striated muscles which appear during pituitary cell culture. In the present immunocytochemical study, cytological alterations of FS cells in vitro were investigated by using antibodies to marker proteins (i.e., S-100 and vimentin) for FS cells. Expression of skeletal muscle-specific MyoD1 detected by immunocytochemistry, enabled identification of myogenic cells at a stage when they were still unicellular. Elongated myoblasts containing MyoD1-positive nuclei were found as early as the fifth day of monolayer culture of pituitary cells. The double immunostaining technique showed that some of these myoblasts reacted with antiserum to S-100. Although all of the myoblasts were immunoreactive to vimentin, this marker protein was unable to identify FS cells in vitro because rapidly proliferating fibroblasts were also immunoreactive to vimentin. Since the antiserum to S-100 that we used did not react with already differentiated striated muscle fibers, the demonstration of both MyoD1 and S-100-immunoreactive myoblasts in our pituitary cultures suggests that these myogenic cells are derived from FS cells. The present study does not rule out the possibility that fibroblasts, whose origin is presently unknown, are also involved in myogenesis in pituitary cultures.

    DOI: 10.2108/zsj.15.247

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  • Intersexual differences and seasonal changes in gonadotropin-producing cells in the salamander Hynobius nigrescens

    M Hasumi, S Sasaki, O Hosoya, K Sato, H Haraguchi

    JOURNAL OF HERPETOLOGY   31 ( 1 )   45 - 51   1997年3月

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    記述言語:英語   出版者・発行元:SOC STUDY AMPHIBIANS REPTILES  

    Intersexual differences and annual cytological changes in presumptive gonadotropin-producing cells (gonadotropes) were examined immunohistochemically in mid-sagittal sections of the pituitary gland of adult Hynobius nigrescens by the use of a monoclonal antibody against bullfrog luteinizing hormone beta-subunit (LH beta). Total immunoreactive areas for LH beta and profiles of the pars distalis in the mid-sagittal plane of the gland were estimated with an image analyzer. Gonadotropes consistently were distributed in the pars distalis near the median eminence and the pars intermedia in both sexes throughout the year; an intersexual difference was found in their distribution pattern. Gonadotrope cells other than these consistent ones distributed in the peripheral region of the pars distalis frequently were observed in females, but not in males. The proportion of gonadotropes among all pars distalis cells, as well as the mean area and number of gonadotropes, was significantly greater in females than in males throughout the year. In males that had a typical aquatic-phase morph and actively exhibited reproductive behavior, both area and number of gonadotropes, as well as profile estimates of pars distalis size, were the greatest of all monthly values. In females, gonadotrope cells increased in area and number from July-January during the terrestrial phase of the nonbreeding season. This increase was concurrent with the development of ovaries. This consecutive increase and development may explain the absence of a second oogenic phase during early spring.

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  • Intersexual differences and seasonal changes in gonadotropin-producing cells in the salamander Hynobius nigrescens

    M Hasumi, S Sasaki, O Hosoya, K Sato, H Haraguchi

    JOURNAL OF HERPETOLOGY   31 ( 1 )   45 - 51   1997年3月

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    記述言語:英語   出版者・発行元:SOC STUDY AMPHIBIANS REPTILES  

    Intersexual differences and annual cytological changes in presumptive gonadotropin-producing cells (gonadotropes) were examined immunohistochemically in mid-sagittal sections of the pituitary gland of adult Hynobius nigrescens by the use of a monoclonal antibody against bullfrog luteinizing hormone beta-subunit (LH beta). Total immunoreactive areas for LH beta and profiles of the pars distalis in the mid-sagittal plane of the gland were estimated with an image analyzer. Gonadotropes consistently were distributed in the pars distalis near the median eminence and the pars intermedia in both sexes throughout the year; an intersexual difference was found in their distribution pattern. Gonadotrope cells other than these consistent ones distributed in the peripheral region of the pars distalis frequently were observed in females, but not in males. The proportion of gonadotropes among all pars distalis cells, as well as the mean area and number of gonadotropes, was significantly greater in females than in males throughout the year. In males that had a typical aquatic-phase morph and actively exhibited reproductive behavior, both area and number of gonadotropes, as well as profile estimates of pars distalis size, were the greatest of all monthly values. In females, gonadotrope cells increased in area and number from July-January during the terrestrial phase of the nonbreeding season. This increase was concurrent with the development of ovaries. This consecutive increase and development may explain the absence of a second oogenic phase during early spring.

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  • Possible involvement of folliculo-stellate cells in the differentiation of muscle fibers during monolayer culture of pituitary cells

    O Hosoya, YG Watanabe

    ZOOLOGICAL SCIENCE   14 ( 1 )   141 - 145   1997年2月

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    記述言語:英語   出版者・発行元:ZOOLOGICAL SOC JAPAN  

    A major objective of the present study was to examine the possibility that non-granular folliculo-stellate (FS) cells in the rat anterior pituitary are involved in the myogenesis that occurs during pituitary cell culture. Enzymatically dissociated anterior pituitary cells were fractionated by use of the Percoll gradient method. The proportion of FS cells was 5.8% on average before cell fractionation. After employing the Percoll gradient procedure, FS cells were enriched to a ratio of 12.2%. Three of five cell fractions were separately cultured, and the incidence of striated muscle fibers was quantitatively investigated. There was a good correlation between the numbers of muscle fibers and the proportions of FS cells in the fractions obtained from the Percoll gradient. These results suggest that FS cells are the cells that transform into striated muscles in pituitary monolayer cultures.

    DOI: 10.2108/zsj.14.141

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  • Possible involvement of folliculo-stellate cells in the differentiation of muscle fibers during monolayer culture of pituitary cells

    Osamu Hosoya, Yuichi G. Watanabe

    Zoological Science   14 ( 1 )   141 - 145   1997年

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    記述言語:英語   出版者・発行元:Zoological Society of Japan  

    A major objective of the present study was to examine the possibility that non-granular folliculostellate (FS) cells in the rat anterior pituitary are involved in the myogenesis that occurs during pituitary cell culture. Enzymatically dissociated anterior pituitary cells were fractionated by use of the Percoll gradient method. The proportion of FS cells was 5.8% on average before cell fractionation. After employing the Percoll gradient procedure, FS cells were enriched to a ratio of 12.2%. Three of five cell fractions were separately cultured, and the incidence of striated muscle fibers was quantitatively investigated. There was a good correlation between the numbers of muscle fibers and the proportions of FS cells in the fractions obtained from the Percoll gradient. These results suggest that FS cells are the cells that transform into striated muscles in pituitary monolayer cultures.

    DOI: 10.2108/zsj.14.141

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講演・口頭発表等

  • 改良型Tet-ONシステムを用いたメダカ網膜桿体特異的な遺伝子発現誘導

    細谷 修, Chung Myung, 安齋 賢, 竹内 秀明, 宮地 まり

    第44回 日本分子生物学会年会  2021年12月2日 

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    開催年月日: 2021年12月1日 - 2021年12月3日

    記述言語:日本語   会議種別:ポスター発表  

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  • メダカDNAトポイソメラーゼIIβによる神経系の遺伝子発現制御

    宮地 まり, 河野 真二, 細谷 修, 竹内 秀明, 筒井 公子, 筒井 研

    第44回 日本分子生物学会年会  2021年12月1日 

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    開催年月日: 2021年12月1日 - 2021年12月3日

    記述言語:日本語  

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  • トポイソメラーゼIIβの遠隔ゲノム部位間での働きを解析するeTIP-seq法の検証

    第42回日本分子生物学会年会  2019年12月 

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    開催年月日: 2019年12月3日 - 2019年12月6日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • トポイソメラーゼIIβは遠隔ゲノム部位の相同配列間に働いてクロマチンを脱凝縮し神経関連遺伝子の発現に関与する

    第42回日本分子生物学会年会  2019年12月 

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    開催年月日: 2019年12月3日 - 2019年12月6日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Key pathways and genes influenced by a drug, NK-4 (Lumin), in Royal College Surgeon Rats

    Shihui Liu, Toshihiko Matsuo, Mary Miyaji, Osamu Hosoya

    ARVO Annual Meeting  2019年5月 

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    開催年月日: 2019年4月28日 - 2019年5月2日

    記述言語:英語   会議種別:ポスター発表  

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  • トポイソメラーゼIIβは神経細胞終末分化において遠隔ゲノム部位の相同配列間に働きクロマチン脱凝縮を誘導する

    宮地まり, 古田良平, 細谷 修, 佐野訓明, 筒井公子, 筒井 研

    第36回染色体ワークショップ 第17回核ダイナミクス研究会  2019年1月24日 

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    開催年月日: 2019年1月23日 - 2019年1月25日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

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  • Key pathways and genes influenced by a drug, NK-4 (Lumin), in human neurons and Royal College Surgeon Rats

    Shihui Liu, Toshihiko Matsuo, Mary Miyaji, Osamu Hosoya

    ARVO Annual Meeting  2018年5月 

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    開催年月日: 2018年4月29日 - 2018年5月3日

    記述言語:英語   会議種別:ポスター発表  

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  • A new knock-out mouse model (MGST2 gene knock-out) for strabismus

    Chaomulige, Toshihiko Matsuo, Shihui Liu, Mary Miyaji, Osamu Hosoya, Izuho Hatada, Takuro Horii

    ARVO Annual Meeting  2020年5月 

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    記述言語:英語  

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  • Prevention of apoptotic photoreceptor cell death by a Cryptocyanine drug (NK-4) during inherited retinal degeneration in RCS rats

    Shihui Liu, Toshihiko Matsuo, Mary Miyaji, Osamu Hosoya

    ARVO Annual Meeting  2020年5月 

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    記述言語:英語  

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  • 網膜色素変性症に対する治療薬候補NK-4, OURePTM, トレハロース点眼薬の紹介

    天津医科大学 眼科国際会議 講演  2019年9月28日 

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

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  • NK4 dye reduces the apoptosis of photoreceptor cells.

    ARVO (The Association for Research in Vision and Ophthalmology) 2017 Annual Meeting  2017年 

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  • 神経細胞終末分化過程でのDNAトポイソメラーゼIIβによるグローバルなクロマチン構造変換を介した遺伝子発現制御機構.

    第33回染色体ワークショップ・第14回核ダイナミクス研究会  2016年 

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  • Apoptosis reduction by a photoelectric dye used for Okayama University-type retinal prosthesis (OURePTM).

    ARVO (The Association for Research in Vision and Ophthalmology) 2016 Annual Meeting  2016年 

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  • DNA topoisomerase IIβ mediates interactions between distal genomic sites within intergenic regions

    第38回日本分子生物学会年会, 第88回日本生化学会大会 合同大会  2015年 

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  • Global changes of chromatin structure during terminal differentiation of neurons are regulated by DNA topoisomerase IIβ complexed with hnRNPU/SAF-A/SP120

    第38回日本分子生物学会年会, 第88回日本生化学会大会 合同大会  2015年 

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  • 神経細胞核の3次元DNA配置と遺伝子発現制御

    バイオイメージバイオインフォマティクスワークショップ2015  2015年 

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  • RNA regulates nuclear dynamics and catalytic activity of topoisomerase IIbeta by binding to a novel domain of the enzyme

    Cell Symposia Regulatory RNAs  2014年 

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  • DNAトポイソメラーゼIIβによる核内構造変化と遺伝子発現制御

    第37回日本分子生物学会年会  2014年 

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  • RNA regulates nuclear dynamics and catalytic activity of topoisomerase IIbeta by binding to a novel domain of the enzyme

    Cell Symposia Regulatory RNAs  2014年 

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  • トポイソメラーゼIIβの酵素活性と核内動体はC末端ドメインへのRNAの結合によって制御されている

    第32回染色体ワークショップ・第13回核ダイナミクス研究会合  2014年 

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  • Vision recovery and retinal apoptosis reduction in RCS rats with Okayama University-type retinal prothesis.

    ARVO (The Association for Research in Vision and Ophthalmology) 2014 Annual Meeting  2014年 

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  • Vision recovery and retinal apoptosis reduction in RCS rats with Okayama University-type retinal prothesis.

    ARVO (The Association for Research in Vision and Ophthalmology) 2014 Annual Meeting  2014年 

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  • Regulatory roles of DNA topoisomerase IIβ in the developing cerebellar neurons.

    第4回国際小脳学会  2011年 

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  • 網膜視細胞の終末分化におけるDNAトポイソメラーゼIIβの役割

    第34回 日本分子生物学会年会  2011年 

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  • DNAトポイソメラーゼⅡβのRNAによる活性調節と核内局在変化

    第34回 日本分子生物学会年会  2011年 

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  • DNAトポイソメラーゼIIβの核内における移動メカニズム

    第33回 日本分子生物学会年会 第83回 日本生化学会大会 合同大会  2010年 

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  • 網膜杆体視細胞の終末分化におけるDNAトポイソメラーゼIIβの関与

    第33回 日本分子生物学会年会 第83回 日本生化学会大会 合同大会  2010年 

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  • 人工網膜からみた網膜神経細胞の機能

    第114回日本解剖学会総会・全国学術集会  2009年 

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  • 網膜リボンシナプスの情報伝達と網膜特異的Amphiphysin-Irの機能

    第114回日本解剖学会総会・全国学術集会  2009年 

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  • Internuclear dostribution of LEDGF/p75/SBP75 in HeLa cells

    2009年 

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  • LEDGF/p75/SBP75の超らせんDNA結合活性と核内局在

    第32回日本分子生物学年会年会  2009年 

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  • DNAトポイソメラーゼIIβと核マトリックスタンパク質SP120/hnRNP U/SAF-Aの複合体形成

    第31回日本分子生物学年会年会 第81回日本生化学会大会 合同大会  2008年 

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  • 転写活性クロマチン領域へのHIV-1 DNA挿入を制御するLEDGF/p75/SBP75のクロマチン認識機構

    第31回日本分子生物学年会年会 第81回日本生化学会大会 合同大会  2008年 

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  • DNAトポイソメラーゼIIβの核質-核小体シャトリング機構

    第31回日本分子生物学年会年会 第81回日本生化学会大会 合同大会  2008年 

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  • トポイソメラーゼIIβによる遺伝子活性化のメカニズム

    細胞核ダイナミクス 第五回班会議  2008年 

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  • Amphiphysin Ir participates in receptor-mediated endocytosis in ARPE-19

    Neuro2007  2007年 

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  • 神経細胞終末分化における遺伝子誘導とトポイソメラーゼIIβの標的

    特定領域研究「細胞核ダイナミクス」第4回班会議  2007年 

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  • Dynamic relocation and sumo-mediated degradation of DNA topoisomerase II beta under chromatin stress

    International symposium: Functional organization of the nucleus  2007年 

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  • 哺乳類II型トポイソメラーゼアイソフォームの動態と機能分担

    第23回染色体ワークショップ  2006年 

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  • AEPR-19細胞における網膜特異的amphiphysin Iスプライスバリアントの局在

    第29回 日本神経科学大会  2006年 

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  • DNA topoisomerase II beta changes chromatin structure that is essential for transcriptional induction in the terminally differentiating neuron

    20th IUBMB International congress of biochemistry and molecular biology and 11th FAOBMB congress  2006年 

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  • 「細胞分化に伴う転写制御を可能にする染色体構造変換のメカニズム」

    第28回日本分子生物学会年会  2005年 

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  • Mechanism of the selective degradation of DNA topoisomerase II beta induced by a catalytic inhibitor ICRF-193

    第78回 日本生化学会大会  2005年 

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  • 核のストレス応答;DNAトポイソメラーゼIIβの誘導的分解

    第5回 細胞核ダイナミクス研究会  2005年 

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  • Molecular mechanism of endocytosis following tonic neurotransmitter release in the retinal ribbon synapses.

    International symposium on nano-biotechnology & 6th international conference on protein phosphatases  2004年 

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  • 網膜リボンシナプスにおけるamphiphysin Irの機能

    第26回日本神経科学大会  2004年 

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  • 神経細胞の分化過程における遺伝子の発現誘導とDNAトポイソメラーゼIIβによるクロマチン高次構造の変化

    第4回細胞核ダイナミクス研究会  2004年 

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  • Binding partners of the retina-specific amphiphysin I variants imply its role in the endocytic process unique to ribbon synapses.

    第77回日本生化学会大会  2004年 

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  • シナプス解析のための免疫組織化学の基礎

    第31回岡山脳研究セミナー  2004年 

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  • DNAトポイソメラーゼIIβ誘導分解におけるSUMO修飾の役割

    第27回日本分子生物学会年会  2004年 

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  • II型DNAトポイソメラーゼ複合体とクロマチン高次構造の変換

    第26回日本分子生物学会年会  2003年 

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  • 網膜リボンシナプスに局在する新規amphiphysin Iスプライスバリアント, amphiphysin Irとその結合タンパク質

    第25回 日本神経科学大会  2002年 

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  • 網膜リボンシナプスに特異的なamphiphysin Iスプライスバリアント

    第24回日本分子生物学会  2001年 

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  • 網膜で発現するシナプスタンパク質amphiphysin Irの局在

    第24回日本神経科学・第44回日本神経化学合同大会(Neuro2001)  2001年 

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▼全件表示

受賞

  • 2014年度日本臓器学会論文賞

    2014年  

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    受賞国:日本国

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  • TOMINAGA AWARD 2012

    2013年  

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    受賞国:日本国

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共同研究・競争的資金等の研究

  • 網膜視細胞におけるトポイソメラーゼIIβの生理、病理学的役割の検証

    研究課題/領域番号:21K09721  2021年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    細谷 修

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    本研究の目的は、小型硬骨魚類メダカの桿体視細胞(桿体)を解析モデルに、成熟期以降の視細胞および網膜視機能におけるトポイソメラーゼIIβ(TopIIβ)が果たす役割を明らかにするとともに、網膜変性疾患の発症やその病態への関与の可能性を検証することである。令和3年度は、終末分化後の任意の時期(成熟期, 老齢期)に桿体限定的にTopIIβ遺伝子の機能阻害または破壊を誘起出来るトランスジェニック・メダカ系統の作出に取り組んだ。まず初めに、抗生物質テトラサイクリンの誘導体であるドキシサイクリン(Dox)を投与することでメダカの桿体特異的に任意のタイミングで、かつ可逆的な導入遺伝子の誘導発現を可能にする新規テトラサイクリン遺伝子発現調節(newTet-ON)システムの開発に着手して、その実用化に成功した(論文および学会で発表)。続いて、TopIIβ遺伝子の発現量をノックダウンさせる目的で、newTet-ONシステムとCRISPR/Cas9システムを用いたトランスジェニック・メダカ2系統:Tg(U6-TopIIβ-gRNA) (RNA pol III系プロモーター制御下に全身性にゲノム上のTopIIβ遺伝子の特定DNA配列を標的とするガイドRNAを発現) とTg(Rho-Cas9)(ロドプシンプロモーター制御下でDox存在時にのみ桿体特異的にCas9 nucleaseを発現する系統)の作出と、交配によるダブルトランスジェニック・メダカの作出が出来た。現在さらに、TopIIβ遺伝子の発現を完全にノックアウトさせる目的で、newTet-ONシステムとCre/loxPシステムの組み合わからなるダブルトランスジェニック・メダカ系統の作出に取り組んでいる。

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  • 岡山大学方式人工網膜(OURep)の製造品質管理とfirst-in-human医師主導治験

    研究課題/領域番号:18950217  2018年04月 - 2021年03月

    国立研究開発法人日本医療研究開発機構  日本医療研究開発機構研究費  難治性疾患等実用化研究事業 難治性疾患実用化研究事業

    松尾俊彦, 内田哲也, 櫻井淳, 蔵本孝一, 細谷修

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    担当区分:研究分担者  資金種別:競争的資金

    配分額:780000円

  • 岡山大学方式人工網膜(OURep)の製造品質管理とfirst-in-human医師主導治験

    研究課題/領域番号:18950217  2018年04月 - 2021年03月

    国立研究開発法人日本医療研究開発機構  難治性疾患実用化研究事業 

    松尾俊彦, 内田哲也, 櫻井淳, 蔵本孝一, 細谷修

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    担当区分:研究分担者 

    配分額:780000円

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  • SP120による知的障害関連遺伝子の発現制御

    2013年04月 - 2014年03月

    新潟大学脳研究所  脳神経病理標本資源活用の先端的共同研究拠点 

    宮地まり, 宮下哲典, 筒井公子, 細谷修, 佐野訓明, 古田良平

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    担当区分:研究分担者 

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  • 遠隔ゲノム部位間の相互作用におけるII型DNAトポイソメラーゼの役割

    研究課題/領域番号:23310133  2011年04月 - 2014年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    筒井 研, 宮地 まり, 細谷 修, 佐野 訓明, 筒井 公子, 桑野 良三

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    配分額:20410000円 ( 直接経費:15700000円 、 間接経費:4710000円 )

    本研究では、神経細胞の終末分化過程でトポイソメラーゼIIβ(トポIIβ)とSP120が標的とするゲノム部位を、新世代シークエンサーで網羅的に同定することによって、この時期に特徴的な遺伝子発現の調節機構を探り、以下の結果を得た。①トポIIβは一群の遺伝子の転写を、促進と抑制の両方向に調節している。②トポIIβが制御する遺伝子は特徴あるゲノムポジションを占めている。③トポIIβの作用点の一つ(Ts3)は終末分化における遺伝子発現で重要な役割を持つことが示唆された。④Ts3と重なるSP120結合サイトは核内の共局在部位としても同定された。⑤Ts3はトポIIβを介する遠隔相互作用部位そのものである。

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  • LA遺伝子の発現と精神・神経疾患

    2010年04月 - 2012年03月

    新潟大学脳研究所  脳神経病理標本資源活用の先端的共同研究拠点 

    筒井研, 宮地まり, 古田良平, 細谷修, 筒井公子, 桑野良三

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    担当区分:研究分担者 

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  • 網膜色素上皮細胞におけるamphiphysinバリアントの役割

    研究課題/領域番号:19791268  2007年 - 2008年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    細谷 修, 筒井 公子, 筒井 研

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    配分額:3350000円 ( 直接経費:2900000円 、 間接経費:450000円 )

    Amphiphysin Ir(amph Ir)は網膜に特有なエンドサイトーシス関連タンパク質である. このタンパク質は, 感覚神経性網膜のリボンシナプス部と網膜色素上皮層に強く発現する. 本研究ではヒト網膜色素上皮培養細胞株(ARPE-19)を実験モデルに用い,ヒト網膜色素上皮層に発現するamph Irの果たす役割を調べた. その結果, 色素上皮細胞のトランスフェリン受容体介在型エンドサイトーシス経路の細胞内輸送過程にamph Irが関与することが分かった.

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  • 誘導型RNAi法の開発とこれを用いた網膜リボンシナプス情報伝達の分子機構の解明

    研究課題/領域番号:16791048  2004年 - 2005年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    細谷 修

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    配分額:2800000円 ( 直接経費:2800000円 )

    Amphiphysin I(amph I)は、神経細胞の軸索終末部でシナプス小胞膜のエンドサートーシス過程に関与するタンパク質の一つである。これまでにヒト網膜cDNAライブラリーのクローニングと特異抗体を用いた生化学・免疫組織化学的な解析を行い、網膜特異的に発現するamph Iバリアント(amph Ir)の存在を見いだした。Amph Irには複数のオルタナティブスプライスフォームがあり、これらはリボンシナプス特異的に発現するタイプと網膜色素上皮に強発現するタイプに大別できる。リボンシナプスは網膜における視覚情報の伝達に重要な構造であり、色素上皮は神経網膜の健常性の維持に不可欠な組織であるが、そこで働く分子群や分子機構については不明な点が多い。Amph Irの生理機能の解明は、網膜での視機能発現・維持の仕組みを理解する上で重要な研究課題と考えられる。
    本研究ではamph Ir遺伝子特異的なRNAi現象を誘起するsiRNA発現ベクターの作製を行い、これまでに以下の成果を得た。
    1)Amph Ir遺伝子配列に対するsiRNAターゲットサイトをヒトおよびラットで予測した。
    2)PCRを利用したヘアピンタイプのsiRNA発現DNAカセットの合成法を確立した。
    3)合成siRNA発現DNAカセットと培養細胞を用いた、迅速かつ簡便なsiRNA標的配列のスクリーニング法を確立し、高いRNAi効果を示すsiRNAを得た。
    4)siRNA発現カセットとマーカー遺伝子発現配列を併せ持つ、siRNA発現ベクターをプラスミドベースで作製した。
    5)培養細胞を用いた解析から、作製したsiRNA発現ベクターが機能することが確認された。内因性に発現するamph Irに対するRNAi効果については、検討中である。

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  • 網膜リボンシナプスにおける視覚情報伝達の分子メカニズムの研究

    研究課題/領域番号:15659413  2003年

    日本学術振興会  科学研究費助成事業  萌芽研究

    筒井 公子, 細谷 修

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    配分額:1900000円 ( 直接経費:1900000円 )

    視覚情報は神経伝達物質の高速で持続的なリリースにより伝達され,刺激を受けた時のみ伝達物質を放出する普遍的な神経情報伝達とメカニズムが明らかに異なる.網膜では,シナプス小胞膜回収(エンドサイトーシス)に必須のアンフィファイシンIに580アミノ酸残基の挿入された新規バリアント,アンフィファイシンIr(amph Ir)が発現していることを我々は2002年に報告したが,本研究でamph Irが視覚情報伝達の根幹となる網膜リボンシナプスのプレシナプスに特異的に局在し,持続的な神経伝達物質放出に対応した効率的なエンドサイトーシスの分子メカニズムに密接に関与して機能している事を明らかにした.(Eur.J.Neurosci.,2004 in press)
    1,amph Ir抗体による免疫電子顕微鏡観察,および各種シナプス関連タンパク質に対する特異抗体との二重蛍光組織染色・共焦点レーザー顕微鏡観察で,amph Irがリボンシナプスに特異的で,しかもプレシナプスにのみ発現していることを明らかにした.
    2,amph Irは従来型amph Iの2カ所に挿入を持つバリアントであるが,amph Iのドメイン構造は保たれている.抗amph Ir特異抗体による免疫沈降で,amph Irはin vivoでamph II (アンフィファイシンII,amph Iのアイソフォーム)とヘテロコンプレックスを形成し,エンドサイトーシス関連タンパク質ダイナミン,クラスリン,α-アダプチンと複合体を構成していることを証明した.Amph Ir複合体構成タンパク質はリボンシナプス内でamph Irと共局在することが示された.
    3,全長を発現させたamph Ir-GST融合タンパク質を用いたプルダウン法とマススペクトルによるプロテオーム解析により,α-adducinがamph Irと結合することを見出した.Amph Irの関与する新規エンドサイトーシス機構の存在を示唆しており,現在解析を進めている.

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  • 網膜特異的なamphiphysin Iバリアントの網膜内局在の免疫組織化学的解析

    研究課題/領域番号:13670014  2001年 - 2002年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    細谷 修, 筒井 公子

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    配分額:1400000円 ( 直接経費:1400000円 )

    Amphiphysin I(以下amph I)はニューロンの軸索終末に強く発現し、amph Iのアイソフォームであるamphiphysin II(amph II)とともに、シナプス小胞膜のクラスリン介在性エンドサイトーシスに関与するタンパク質である。我々はヒト網膜のcDNAクローニングを行い、従来型のamph Iの他に3アミノ酸残基と数百アミノ酸残基からなる2つの挿入部分をもつ新規のamph Iスプライスバリアント(amph Ir)が網膜特異的に発現することをヒトおよびラットで見いだし、このバリアントの網膜における生理的機能の解明を試みている。
    平成13年度は、amph Irのみを特異的に認識するポリクローナル抗体を作製し、この抗体を用いてラット網膜におけるamph Irの局在を免疫組織化学的に検索した。その結果、amph Irは視細胞(桿体と錐体)と双極細胞の軸索終末部に特異的に存在することが明らかとなり、amph Irが網膜リボンシナプス機能に関与する可能性を示した。
    平成14年度は、免疫沈降法とイムノブロットを用いてamph Irと相互作用するタンパク質の検索を行った。免疫沈降複合体に含まれるタンパク質として、これまでにamph II, clathrin,およびactinを同定した。さらに、amph Irとこれらのタンパク質が視細胞と双極細胞の軸索終末で共局在することを蛍光二重標識法により確認した。これらの結果から、amph Irが網膜リボンシナプスで1)クラスリン依存性のシナプス小胞膜回収機構へ関与する可能性、2)アクチン細胞骨格系と機能的連携をもつ可能性が考えられ、現在解析を進めている。

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その他研究活動

  • 岡山大学方式人工網膜(OURep)の製造品質管理とfirst-in-human医師主導治験

    2018年04月
    -
    現在

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    岡山大学インキュベーション・クリーンルームでのQMS体制による治験機器製造. 品質管理指標の測定精度の向上. 治験機器の品質保証期間の設定. 生物学的反応に基づく品質管理の規格確立・運用.First-in-human feasibility study医師主導治験への治験機器提供に関わる.
    岡山大学大学院ヘルスシステム統合科学研究科・医学部医学科眼科学兼任・岡山大学病院(准教授 松尾俊彦)との共同研究.

  • 新規斜視関連遺伝子の解析

    2017年12月
    -
    現在

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    斜視遺伝子候補のMGST2のノックアウトマウスを作製, 解析する.
    群馬大学生体調節研究所ゲノムリソースセンターの畑田先生, 岡山大学大学院ヘルスシステム統合科学研究科・医学部医学科眼科学兼任・岡山大学病院(准教授 松尾俊彦)との共同研究.

  • 新規網膜視細胞保護作用薬の開発

    2007年04月
    -
    現在

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    岡山大学方式の人工網膜に使用している光電気変換色素のもつ網膜視細胞保護作用のメカニズムの解明. ならびに, 機能性色素 (NK-4) の網膜視細胞保護作用のメカニズムの解明. 岡山大学大学院ヘルスシステム統合科学研究科・医学部医学科眼科学兼任・岡山大学病院(准教授 松尾俊彦)との共同研究.

 

担当授業科目

  • 人体の構造:入門 (2023年度) 特別  - その他

  • 医学研究インターンシップ (2023年度) 特別  - その他

  • 基礎病態演習 (2023年度) 特別  - その他

  • 神経構造学 (2023年度) 特別  - その他

  • 神経構造学実習 (2023年度) 特別  - その他

  • 脳神経機構学実習 (2023年度) 特別  - その他

  • 脳神経機構学演習 (2023年度) 特別  - その他

  • 脳神経機構学I(演習・実習) (2023年度) 特別  - その他

  • 脳神経機構学I(講義・演習) (2023年度) 特別  - その他

  • 脳神経機構学II(演習・実習) (2023年度) 特別  - その他

  • 脳神経機構学II(講義・演習) (2023年度) 特別  - その他

  • 人体の構造:入門 (2022年度) 特別  - その他

  • 人体構造学 (2022年度) 集中  - その他

  • 医学研究インターンシップ (2022年度) 特別  - その他

  • 基礎病態演習 (2022年度) 特別  - その他

  • 神経構造学 (2022年度) 特別  - その他

  • 神経構造学実習 (2022年度) 特別  - その他

  • 脳神経機構学I(演習・実習) (2022年度) 特別  - その他

  • 脳神経機構学I(講義・演習) (2022年度) 特別  - その他

  • 脳神経機構学II(演習・実習) (2022年度) 特別  - その他

  • 脳神経機構学II(講義・演習) (2022年度) 特別  - その他

  • 人体の構造:入門 (2021年度) 特別  - その他

  • 人体構造学 (2021年度) 集中  - その他

  • 医学研究インターンシップ (2021年度) 特別  - その他

  • 基礎病態演習 (2021年度) 特別  - その他

  • 神経構造学 (2021年度) 特別  - その他

  • 神経構造学実習 (2021年度) 特別  - その他

  • 脳神経機構学I(演習・実習) (2021年度) 特別  - その他

  • 脳神経機構学I(講義・演習) (2021年度) 特別  - その他

  • 脳神経機構学II(演習・実習) (2021年度) 特別  - その他

  • 脳神経機構学II(講義・演習) (2021年度) 特別  - その他

  • 人体の構造:入門 (2020年度) 特別  - その他

  • 人体構造学 (2020年度) 集中  - その他

  • 神経構造学 (2020年度) 特別  - その他

  • 神経構造学実習 (2020年度) 特別  - その他

  • 脳神経機構学I(演習・実習) (2020年度) 特別  - その他

  • 脳神経機構学I(講義・演習) (2020年度) 特別  - その他

  • 脳神経機構学II(演習・実習) (2020年度) 特別  - その他

  • 脳神経機構学II(講義・演習) (2020年度) 特別  - その他

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社会貢献活動

  • 地域医療教育 (講義)

    役割:講師

    新見公立短期大学, 岡山赤十字看護専門学校, CAC医療専門学校, 玉野総合医療専門学校  2001年4月1日 - 2016年3月31日

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    対象: 大学生

    種別:その他

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  • 地域医療教育 (講義)

    役割:講師

    岡山大学, 新見公立短期大学, 岡山赤十字看護専門学校, CAC医療専門学校, 玉野総合医療専門学校  岡山大学, 新見公立短期大学, 岡山赤十字看護専門学校, CAC医療専門学校, 玉野総合医療専門学校  1998年4月 - 現在

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    対象: 大学生, 大学院生

    種別:その他

    大学および専門学校で基礎医学科目 (解剖学) の講義を担当し, 医療従事者教育に携わる.

メディア報道

  • 光電変換色素NK-5962の網膜視細胞保護の分子機構を発見! インターネットメディア

    岡山大学  http://www.okayama-u.ac.jp/tp/release/release_id916.html  2022年1月

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    執筆者:本人以外 

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  • 機能性色素NK-4の網膜視細胞の保護効果を発見. インターネットメディア

    岡山大学  http://www.okayama-u.ac.jp/tp/release/release_id870.html  2021年8月

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    執筆者:本人以外 

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  • 神経活動に必要な遺伝子が、ゲノムDNAの結び目でON-OFFされていることを明らかに インターネットメディア

    岡山大学  http://www.okayama-u.ac.jp/tp/release/release_id776.html  2020年10月

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    執筆者:本人以外 

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  • 人工網膜の意志主導治験に向けての有効性を証明~岡山大学方式人工網膜「OUReP(TM)」がラットの視覚誘導電位を改善~ インターネットメディア

    岡山大学  http://www.okayama-u.ac.jp/tp/release/release_id452.html  2017年3月

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学術貢献活動

  • 第47回岡山脳研究セミナー

    脳神経機構学  ( 岡山大学 ) 2022年1月25日

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    種別:学会・研究会等 

  • メタルバイオサイエンス研究会 2017

    役割:企画立案・運営等

    ( 岡山大学 ) 2017年10月13日 - 2017年10月14日

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    種別:学会・研究会等 

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  • Acta Medica Okayama 国際学術貢献

    役割:査読

    ( 岡山大学 ) 2012年

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    種別:査読等 

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  • 岡山脳研究セミナー

    役割:企画立案・運営等

    ( 岡山大学 ) 2010年3月13日

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    種別:学会・研究会等 

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  • 第114回日本解剖学会総会・全国学術集会

    役割:企画立案・運営等

    ( 岡山大学 (岡山理科大学) ) 2009年3月28日 - 2009年3月30日

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    種別:学会・研究会等 

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  • 篤志解剖全国連合会第39回総会

    役割:企画立案・運営等

    ( 岡山大学 ) 2009年3月28日 - 2009年3月30日

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