2022/12/01 更新

写真a

タイナカ カズキ
田井中 一貴
TAINAKA Kazuki
所属
脳研究所 教授
職名
教授
外部リンク

学位

  • 博士(工学) ( 2006年3月   京都大学 )

研究キーワード

  • Bioorganic Chemistry

  • Photochemistry

  • 組織透明化

  • 神経病理学

  • ケミカルバイオロジー

  • イメージング

研究分野

  • ライフサイエンス / 神経形態学

  • ナノテク・材料 / 生体化学

経歴(researchmap)

  • 新潟大学   脳研究所   教授

    2021年6月 - 現在

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    国名:日本国

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  • 新潟大学   脳研究所   テニュア・トラック教授

    2018年10月 - 2021年5月

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  • 新潟大学   脳研究所   特任教授

    2017年1月 - 2018年9月

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  • 東京大学   医学系研究科   講師

    2013年4月 - 2016年12月

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  • 理化学研究所   生命システム研究センター   研究員

    2010年10月 - 2013年3月

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  • 京都大学   エネルギー理工学研究所   助教

    2008年2月 - 2010年9月

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  • 大阪大学   産業科学研究所   日本学術振興会特別研究員(PD)

    2007年4月 - 2008年1月

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  • 大阪大学   産業科学研究所   特任研究員

    2006年10月 - 2007年3月

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  • 理化学研究所   岡本独立主幹研究ユニット   ユニット研究員

    2006年4月 - 2006年9月

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  • 京都大学   工学研究科   日本学術振興会特別研究員(DC1)

    2003年4月 - 2006年3月

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▶ 全件表示

経歴

  • 新潟大学   脳研究所 基礎神経科学部門   教授

    2020年4月 - 現在

  • 新潟大学   脳研究所 生命科学リソース研究センター   教授

    2018年10月 - 2020年3月

  • 新潟大学   脳研究所   特任教授

    2017年1月 - 2018年9月

学歴

  • 京都大学   工学研究科   合成・生物化学専攻

    2001年4月 - 2006年3月

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  • 京都大学   工学部   工業化学科

    1997年4月 - 2001年3月

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所属学協会

 

論文

  • Cerebrocortical activation following unilateral labyrinthectomy in mice characterized by whole-brain clearing: implications for sensory reweighting. 国際誌

    Ryota Kai, Kuniyuki Takahashi, Kazuki Tainaka, Yuriko Iwakura, Hisaaki Namba, Nae Saito, Toshikuni Sasaoka, Shun Yamaguchi, Hiroyuki Nawa, Arata Horii

    Scientific reports   12 ( 1 )   15424 - 15424   2022年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Posture and gait are maintained by sensory inputs from the vestibular, visual, and somatosensory systems and motor outputs. Upon vestibular damage, the visual and/or somatosensory systems functionally substitute by cortical mechanisms called "sensory reweighting". We investigated the cerebrocortical mechanisms underlying sensory reweighting after unilateral labyrinthectomy (UL) in mice. Arc-dVenus transgenic mice, in which the gene encoding the fluorescent protein dVenus is transcribed under the control of the promoter of the immediate early gene Arc, were used in combination with whole-brain three-dimensional (3D) imaging. Performance on the rotarod was measured as a behavioral correlate of sensory reweighting. Following left UL, all mice showed the head roll-tilt until UL10, indicating the vestibular periphery damage. The rotarod performance worsened in the UL mice from UL1 to UL3, which rapidly recovered. Whole-brain 3D imaging revealed that the number of activated neurons in S1, but not in V1, in UL7 was higher than that in sham-treated mice. At UL7, medial prefrontal cortex (mPFC) and agranular insular cortex (AIC) activation was also observed. Therefore, sensory reweighting to the somatosensory system could compensate for vestibular dysfunction following UL; further, mPFC and AIC contribute to the integration of sensory and motor functions to restore balance.

    DOI: 10.1038/s41598-022-19678-4

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  • Spatiotemporal dynamics of clonal selection and diversification in normal endometrial epithelium. 国際誌

    Manako Yamaguchi, Hirofumi Nakaoka, Kazuaki Suda, Kosuke Yoshihara, Tatsuya Ishiguro, Nozomi Yachida, Kyota Saito, Haruka Ueda, Kentaro Sugino, Yutaro Mori, Kaoru Yamawaki, Ryo Tamura, Sundaramoorthy Revathidevi, Teiichi Motoyama, Kazuki Tainaka, Roel G W Verhaak, Ituro Inoue, Takayuki Enomoto

    Nature communications   13 ( 1 )   943 - 943   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    It has become evident that somatic mutations in cancer-associated genes accumulate in the normal endometrium, but spatiotemporal understanding of the evolution and expansion of mutant clones is limited. To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we sequence 1311 endometrial glands from 37 women. By collecting endometrial glands from different parts of the endometrium, we show that multiple glands with the same somatic mutations occupy substantial areas of the endometrium. We demonstrate that "rhizome structures", in which the basal glands run horizontally along the muscular layer and multiple vertical glands rise from the basal gland, originate from the same ancestral clone. Moreover, mutant clones detected in the vertical glands diversify by acquiring additional mutations. These results suggest that clonal expansions through the rhizome structures are involved in the mechanism by which mutant clones extend their territories. Furthermore, we show clonal expansions and copy neutral loss-of-heterozygosity events occur early in life, suggesting such events can be tolerated many years in the normal endometrium. Our results of the evolutionary dynamics of mutant clones in the human endometrium will lead to a better understanding of the mechanisms of endometrial regeneration during the menstrual cycle and the development of therapies for the prevention and treatment of endometrium-related diseases.

    DOI: 10.1038/s41467-022-28568-2

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  • Using a new three-dimensional CUBIC tissue-clearing method to examine the brain during experimental cerebral malaria 査読

    Julia Matsuo-Dapaah, Michelle Sue Jann Lee, Ken J Ishii, Kazuki Tainaka, Cevayir Coban

    International Immunology   33 ( 11 )   587 - 594   2021年10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:Oxford University Press (OUP)  

    Abstract

    Cerebral malaria (CM) is a life-threatening complication of the malaria disease caused by Plasmodium falciparum infection and is responsible for the death of half a million people annually. The molecular pathogenesis underlying CM in humans is not completely understood, although sequestration of infected erythrocytes in cerebral microvessels is thought to play a major role. In contrast, experimental cerebral malaria (ECM) models in mice have been thought to be distinct from human CM, and are mainly caused by inflammatory mediators. Here, to understand the spatial distribution and the potential sequestration of parasites in the whole-brain microvessels during a mouse model of ECM, we utilized the new tissue-clearing method CUBIC (Clear, Unobstructed, Brain/Body Imaging Cocktails and Computational analysis) with light-sheet fluorescent microscopy (LSFM), and reconstructed images in three dimensions (3D). We demonstrated significantly greater accumulation of Plasmodium berghei ANKA (PbANKA) parasites in the olfactory bulb (OB) of mice, compared with the other parts of the brain, including the cerebral cortex, cerebellum and brainstem. Furthermore, we show that PbANKA parasites preferentially accumulate in the brainstem when the OB is surgically removed. This study therefore not only highlights a successful application of CUBIC tissue-clearing technology to visualize the whole brain and its microvessels during ECM, but it also shows CUBIC’s future potential for visualizing pathological events in the whole ECM brain at the cellular level, an achievement that would greatly advance our understanding of human cerebral malaria.

    DOI: 10.1093/intimm/dxab060

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    その他リンク: https://academic.oup.com/intimm/article-pdf/33/11/587/44558275/dxab060.pdf

  • Mechanical load regulates bone growth via periosteal Osteocrin. 国際誌

    Haruko Watanabe-Takano, Hiroki Ochi, Ayano Chiba, Ayaka Matsuo, Yugo Kanai, Shigetomo Fukuhara, Naoki Ito, Keisuke Sako, Takahiro Miyazaki, Kazuki Tainaka, Ichiro Harada, Shingo Sato, Yasuhiro Sawada, Naoto Minamino, Shu Takeda, Hiroki R Ueda, Akihiro Yasoda, Naoki Mochizuki

    Cell reports   36 ( 2 )   109380 - 109380   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)  

    Mechanical stimuli including loading after birth promote bone growth. However, little is known about how mechanical force triggers biochemical signals to regulate bone growth. Here, we identified a periosteal-osteoblast-derived secretory peptide, Osteocrin (OSTN), as a mechanotransducer involved in load-induced long bone growth. OSTN produced by periosteal osteoblasts regulates growth plate growth by enhancing C-type natriuretic peptide (CNP)-dependent proliferation and maturation of chondrocytes, leading to elongation of long bones. Additionally, OSTN cooperates with CNP to regulate bone formation. CNP stimulates osteogenic differentiation of periosteal osteoprogenitors to induce bone formation. OSTN binds to natriuretic peptide receptor 3 (NPR3) in periosteal osteoprogenitors, thereby preventing NPR3-mediated clearance of CNP and consequently facilitating CNP-signal-mediated bone growth. Importantly, physiological loading induces Ostn expression in periosteal osteoblasts by suppressing Forkhead box protein O1 (FoxO1) transcription factor. Thus, this study reveals a crucial role of OSTN as a mechanotransducer converting mechanical loading to CNP-dependent bone formation.

    DOI: 10.1016/j.celrep.2021.109380

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  • Three-dimensional understanding of the morphological complexity of the human uterine endometrium 査読

    Manako Yamaguchi, Kosuke Yoshihara, Kazuaki Suda, Hirofumi Nakaoka, Nozomi Yachida, Haruka Ueda, Kentaro Sugino, Yutaro Mori, Kaoru Yamawaki, Ryo Tamura, Tatsuya Ishiguro, Teiichi Motoyama, Yu Watanabe, Shujiro Okuda, Kazuki Tainaka, Takayuki Enomoto

    iScience   24 ( 4 )   102258 - 102258   2021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:Elsevier BV  

    DOI: 10.1016/j.isci.2021.102258

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  • Whole-organ analysis of TGF-β-mediated remodelling of the tumour microenvironment by tissue clearing 国際誌

    Shimpei I. Kubota, Kei Takahashi, Tomoyuki Mano, Katsuhiko Matsumoto, Takahiro Katsumata, Shoi Shi, Kazuki Tainaka, Hiroki R. Ueda, Shogo Ehata, Kohei Miyazono

    Communications Biology   4 ( 1 )   294 - 294   2020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:Springer Science and Business Media LLC  

    <title>Abstract</title>Tissue clearing is one of the most powerful strategies for a comprehensive analysis of disease progression. Here, we established an integrated pipeline that combines tissue clearing, 3D imaging, and machine learning and applied to a mouse tumour model of experimental lung metastasis using human lung adenocarcinoma A549 cells. This pipeline provided the spatial information of the tumour microenvironment. We further explored the role of transforming growth factor-β (TGF-β) in cancer metastasis. TGF-β-stimulated cancer cells enhanced metastatic colonization of unstimulated-cancer cells in vivo when both cells were mixed. RNA-sequencing analysis showed that expression of the genes related to coagulation and inflammation were up-regulated in TGF-β-stimulated cancer cells. Further, whole-organ analysis revealed accumulation of platelets or macrophages with TGF-β-stimulated cancer cells, suggesting that TGF-β might promote remodelling of the tumour microenvironment, enhancing the colonization of cancer cells. Hence, our integrated pipeline for 3D profiling will help the understanding of the tumour microenvironment.

    DOI: 10.1038/s42003-021-01786-y

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    その他リンク: http://www.nature.com/articles/s42003-021-01786-y

  • Neurotransmission through dopamine D1 receptors is required for aversive memory formation and Arc activation in the cerebral cortex. 査読 国際誌

    Nae Saito, Kazuki Tainaka, Tom Macpherson, Takatoshi Hikida, Shun Yamaguchi, Toshikuni Sasaoka

    Neuroscience Research   156   58 - 65   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Dopaminergic neurotransmission is considered to play an important role not only in reward-based learning, but also in aversive learning. Here, we investigated the role of dopaminergic neurotransmission via dopamine D1 receptors (D1Rs) in aversive memory formation in a passive avoidance test using D1R knockdown (KD) mice, in which the expression of D1Rs can conditionally and reversibly be controlled by doxycycline (Dox) treatment. We also performed whole-brain imaging after aversive footshock stimulation in activity-regulated cytoskeleton protein (Arc)-dVenus D1RKD mice, which were crossbred from Arc-dVenus transgenic mice and D1RKD mice, to examine the distribution of Arc-controlled dVenus expression in the hippocampus and cerebral cortex during aversive memory formation. Knockdown of D1R expression following Dox treatment resulted in impaired performance in the passive avoidance test and was associated with a decrease in dVenus expression in the cerebral cortex (visual, somatosensory, and motor cortices), but not the hippocampus, compared with control mice without Dox treatment. These findings indicate that D1R-mediated dopaminergic transmission is critical for aversive memory formation, specifically by influencing Arc expression in the cerebral cortex.

    DOI: 10.1016/j.neures.2020.04.006

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  • Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues. 査読 国際誌

    Etsuo A Susaki, Chika Shimizu, Akihiro Kuno, Kazuki Tainaka, Xiang Li, Kengo Nishi, Ken Morishima, Hiroaki Ono, Koji L Ode, Yuki Saeki, Kazunari Miyamichi, Kaoru Isa, Chihiro Yokoyama, Hiroki Kitaura, Masako Ikemura, Tetsuo Ushiku, Yoshihiro Shimizu, Takashi Saito, Takaomi C Saido, Masashi Fukayama, Hirotaka Onoe, Kazushige Touhara, Tadashi Isa, Akiyoshi Kakita, Mitsuhiro Shibayama, Hiroki R Ueda

    Nature Communications   11 ( 1 )   1982 - 1982   2020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)  

    Whole-organ/body three-dimensional (3D) staining and imaging have been enduring challenges in histology. By dissecting the complex physicochemical environment of the staining system, we developed a highly optimized 3D staining imaging pipeline based on CUBIC. Based on our precise characterization of biological tissues as an electrolyte gel, we experimentally evaluated broad 3D staining conditions by using an artificial tissue-mimicking material. The combination of optimized conditions allows a bottom-up design of a superior 3D staining protocol that can uniformly label whole adult mouse brains, an adult marmoset brain hemisphere, an ~1 cm3 tissue block of a postmortem adult human cerebellum, and an entire infant marmoset body with dozens of antibodies and cell-impermeant nuclear stains. The whole-organ 3D images collected by light-sheet microscopy are used for computational analyses and whole-organ comparison analysis between species. This pipeline, named CUBIC-HistoVIsion, thus offers advanced opportunities for organ- and organism-scale histological analysis of multicellular systems.

    DOI: 10.1038/s41467-020-15906-5

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  • Rapid chemical clearing of white matter in the post-mortem human brain by 1,2-hexanediol delipidation. 査読

    Inoue M, Saito R, Kakita A, Tainaka K

    Bioorganic Medicinal Chemistry Letters   29 ( 15 )   1886 - 1890   2019年8月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents 査読 国際誌

    Kazuki Tainaka, Tatsuya C. Murakami, Etsuo A. Susaki, Chika Shimizu, Rie Saito, Kei Takahashi, Akiko Hayashi-Takagi, Hiroshi Sekiya, Yasunobu Arima, Satoshi Nojima, Masako Ikemura, Tetsuo Ushiku, Yoshihiro Shimizu, Masaaki Murakami, Kenji F. Tanaka, Masamitsu Iino, Haruo Kasai, Toshikuni Sasaoka, Kazuto Kobayashi, Kohei Miyazono, Eiichi Morii, Tadashi Isa, Masashi Fukayama, Akiyoshi Kakita, Hiroki R. Ueda

    Cell Reports   24 ( 8 )   2196 - 2210.e9   2018年8月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    We describe a strategy for developing hydrophilic chemical cocktails for tissue delipidation, decoloring, refractive index (RI) matching, and decalcification, based on comprehensive chemical profiling. More than 1,600 chemicals were screened by a high-throughput evaluation system for each chemical process. The chemical profiling revealed important chemical factors: salt-free amine with high octanol/water partition-coefficient (logP) for delipidation, N-alkylimidazole for decoloring, aromatic amide for RI matching, and protonation of phosphate ion for decalcification. The strategic integration of optimal chemical cocktails provided a series of CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) protocols, which efficiently clear mouse organs, mouse body including bone, and even large primate and human tissues. The updated CUBIC protocols are scalable and reproducible, and they enable three-dimensional imaging of the mammalian body and large primate and human tissues. This strategy represents a future paradigm for the rational design of hydrophilic clearing cocktails that can be used for large tissues.

    DOI: 10.1016/j.celrep.2018.07.056

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  • A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing 査読

    Tatsuya C. Murakami, Tomoyuki Mano, Shu Saikawa, Shuhei A. Horiguchi, Daichi Shigeta, Kousuke Baba, Hiroshi Sekiya, Yoshihiro Shimizu, Kenji F. Tanaka, Hiroshi Kiyonari, Masamitsu Iino, Hideki Mochizuki, Kazuki Tainaka, Hiroki R. Ueda

    Nature Neuroscience   21 ( 4 )   625 - 637   2018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:Nature Publishing Group  

    A three-dimensional single-cell-resolution mammalian brain atlas will accelerate systems-level identification and analysis of cellular circuits underlying various brain functions. However, its construction requires efficient subcellular-resolution imaging throughout the entire brain. To address this challenge, we developed a fluorescent-protein-compatible, whole-organ clearing and homogeneous expansion protocol based on an aqueous chemical solution (CUBIC-X). The expanded, well-cleared brain enabled us to construct a point-based mouse brain atlas with single-cell annotation (CUBIC-Atlas). CUBIC-Atlas reflects inhomogeneous whole-brain development, revealing a significant decrease in the cerebral visual and somatosensory cortical areas during postnatal development. Probabilistic activity mapping of pharmacologically stimulated Arc-dVenus reporter mouse brains onto CUBIC-Atlas revealed the existence of distinct functional structures in the hippocampal dentate gyrus. CUBIC-Atlas is shareable by an open-source web-based viewer, providing a new platform for whole-brain cell profiling.

    DOI: 10.1038/s41593-018-0109-1

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  • Temperature-Sensitive Substrate and Product Binding Underlie Temperature-Compensated Phosphorylation in the Clock 査読

    Yuta Shinohara, Yohei M. Koyama, Maki Ukai-Tadenuma, Takatsugu Hirokawa, Masaki Kikuchi, Rikuhiro G. Yamada, Hideki Ukai, Hiroshi Fujishima, Takashi Umehara, Kazuki Tainaka, Hiroki R. Ueda

    MOLECULAR CELL   67 ( 5 )   783 - +   2017年9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:CELL PRESS  

    Temperature compensation is a striking feature of the circadian clock. Here we investigate biochemical mechanisms underlying temperature-compensated, CKI delta-dependent multi-site phosphorylation in mammals. We identify two mechanisms for temperature-insensitive phosphorylation at higher temperature: lower substrate affinity to CKI delta-ATP complex and higher product affinity to CKI delta-ADP complex. Inhibitor screening of ADP-dependent phosphatase activity of CKI delta identified aurintricar-boxylic acid (ATA) as a temperature-sensitive kinase activator. Docking simulation of ATA and mutagenesis experiment revealed K224D/K224E mutations in CKI delta that impaired product binding and temperature-compensated primed phosphorylation. Importantly, K224D mutation shortens behavioral circadian rhythms and changes the temperature dependency of SCN's circadian period. Interestingly, temperature-compensated phosphorylation was evolutionary conserved in yeast. Molecular dynamics simulation and X-ray crystallography demonstrate that an evolutionally conserved CKI-specific domain around K224 can provide a structural basis for temperature-sensitive substrate and product binding. Surprisingly, this domain can confer temperature compensation on a temperature-sensitive TTBK1. These findings suggest the temperature-sensitive substrate-and product-binding mechanisms underlie temperature compensation.

    DOI: 10.1016/j.molcel.2017.08.009

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  • Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution 査読

    Shimpei I. Kubota, Kei Takahashi, Jun Nishida, Yasuyuki Morishita, Shogo Ehata, Kazuki Tainaka, Kohei Miyazono, Hiroki R. Ueda

    CELL REPORTS   20 ( 1 )   236 - 250   2017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)   出版者・発行元:CELL PRESS  

    Stochastic and proliferative events initiated from a single cell can disrupt homeostatic balance and lead to fatal disease processes such as cancer metastasis. To overcome metastasis, it is necessary to detect and quantify sparsely distributed metastatic cells throughout the body at early stages. Here, we demonstrate that clear, unobstructed brain/ body imaging cocktails and computational analysis (CUBIC)-based cancer (CUBIC-cancer) analysis with a refractive index (RI)=optimized protocol enables comprehensive cancer cell profiling of the whole body and organs. We applied CUBIC-cancer analysis to 13 mouse models using nine cancer cell lines and spatiotemporal quantification of metastatic cancer progression at single-cell resolution. CUBIC-cancer analysis suggests that the epithelial-mesenchymal transition promotes not only extravasation but also cell survival at metastatic sites. CUBIC-cancer analysis is also applicable to pharmacotherapeutic profiling of anti-tumor drugs. CUBIC-cancer analysis is compatible with in vivo bioluminescence imaging and 2D histology. We suggest that a scalable analytical pipeline with these three modalities may contribute to addressing currently incurable metastatic diseases.

    DOI: 10.1016/j.celrep.2017.06.010

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  • Chemical Principles in Tissue Clearing and Staining Protocols for Whole-Body Cell Profiling 査読

    Kazuki Tainaka, Akihiro Kuno, Shimpei I. Kubota, Tatzya Murakami, Hiroki R. Ueda

    ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 32   32   713 - 741   2016年

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:ANNUAL REVIEWS  

    Mammalian bodies have more than a billion cells per cubic centimeter, which makes whole-body cell (WBC) profiling of an organism one of the ultimate challenges in biology and medicine. Recent advances in tissue-clearing technology have enabled rapid and comprehensive cellular analyses in whole organs and in the whole body by a combination of state-of-the-art technologies of optical imaging and image informatics. In this review, we focus mainly on the chemical principles in currently available techniques for tissue clearing and staining to facilitate our understanding of their underlying mechanisms. Tissue clearing is usually conducted by the following steps: (a) fixation, (b) permeabilization, (c) decolorizing, and (d) refractive index (RI) matching. To phenotype individual cells after tissue clearing, it is important to visualize genetically encoded fluorescent reporters and/or to stain tissues with fluorescent dyes, fluorescent labeled antibodies, or nucleic acid probes. Although some technical challenges remain, the chemical principles in tissue clearing and staining for WBC profiling will enable various applications, such as identifying cellular circuits across multiple organs and measuring their dynamics in stochastic and proliferative cellular processes, for example, autoimmune and malignant neoplastic diseases.

    DOI: 10.1146/annurev-cellbio-111315-125001

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  • Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging 査読

    Etsuo A. Susaki, Kazuki Tainaka, Dimitri Perrin, Hiroko Yukinaga, Akihiro Kuno, Hiroki R. Ueda

    NATURE PROTOCOLS   10 ( 11 )   1709 - 1727   2015年11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:NATURE PUBLISHING GROUP  

    Here we describe a protocol for advanced CUCUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis). The CUCUBIC protocol enables simple and efficient organ clearing, rapid imaging by light-sheet microscopy and quantitative imaging analysis of multiple samples. The organ or body is cleared by immersion for 1-14 d, with the exact time required dependent on the sample type and the experimental purposes. A single imaging set can be completed in 30-60 min. Image processing and analysis can take &lt;1 d, but it is dependent on the number of samples in the data set. The CUCUBIC clearing protocol can process multiple samples simultaneously. We previously used CUCUBIC to image whole-brain neural activities at single-cell resolution using Arc-dVenus transgenic (Tg) mice. CUCUBIC informatics calculated the Venus signal subtraction, comparing different brains at a whole-organ scale. These protocols provide a platform for organism-level systems biology by comprehensively detecting cells in a whole organ or body.

    DOI: 10.1038/nprot.2015.085

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  • Whole-Body Imaging with Single-Cell Resolution by Tissue Decolorization 査読

    Kazuki Tainaka, Shimpei I. Kubota, Takeru Q. Suyama, Etsuo A. Susaki, Dimitri Perrin, Maki Ukai-Tadenuma, Hideki Ukai, Hiroki R. Ueda

    CELL   159 ( 4 )   911 - 924   2014年11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:CELL PRESS  

    The development of whole-body imaging at single-cell resolution enables system-level approaches to studying cellular circuits in organisms. Previous clearing methods focused on homogenizing mismatched refractive indices of individual tissues, enabling reductions in opacity but falling short of achieving transparency. Here, we show that an aminoalcohol decolorizes blood by efficiently eluting the heme chromophore from hemoglobin. Direct transcardial perfusion of an aminoalcohol-containing cocktail that we previously termed CUBIC coupled with a 10 day to 2 week clearing protocol decolorized and rendered nearly transparent almost all organs of adult mice as well as the entire body of infant and adult mice. This CUBIC-perfusion protocol enables rapid whole-body and whole-organ imaging at single-cell resolution by using light-sheet fluorescent microscopy. The CUBIC protocol is also applicable to 3D pathology, anatomy, and immunohistochemistry of various organs. These results suggest that whole-body imaging of colorless tissues at high resolution will contribute to organism-level systems biology.

    DOI: 10.1016/j.cell.2014.10.034

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  • Whole-Brain Imaging with Single-Cell Resolution Using Chemical Cocktails and Computational Analysis 査読

    Etsuo A. Susaki, Kazuki Tainaka, Dimitri Perrin, Fumiaki Kishino, Takehiro Tawara, Tomonobu M. Watanabe, Chihiro Yokoyama, Hirotaka Onoe, Megumi Eguchi, Shun Yamaguchi, Takaya Abe, Hiroshi Kiyonari, Yoshihiro Shimizu, Atsushi Miyawaki, Hideo Yokota, Hiroki R. Ueda

    CELL   157 ( 3 )   726 - 739   2014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:CELL PRESS  

    Systems-level identification and analysis of cellular circuits in the brain will require the development of whole-brain imaging with single-cell resolution. To this end, we performed comprehensive chemical screening to develop a whole-brain clearing and imaging method, termed CUBIC (clear, unobstructed brain imaging cocktails and computational analysis). CUBIC is a simple and efficient method involving the immersion of brain samples in chemical mixtures containing aminoalcohols, which enables rapid whole-brain imaging with single-photon excitation microscopy. CUBIC is applicable to multicolor imaging of fluorescent proteins or immunostained samples in adult brains and is scalable from a primate brain to subcellular structures. We also developed a whole-brain cell-nuclear counterstaining protocol and a computational image analysis pipeline that, together with CUBIC reagents, enable the visualization and quantification of neural activities induced by environmental stimulation. CUBIC enables time-course expression profiling of whole adult brains with single-cell resolution.

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  • Non-Enzymatic DNA Cleavage Reaction Induced by 5-Ethynyluracil in Methylamine Aqueous Solution and Application to DNA Concatenation 査読

    Shuji Ikeda, Kazuki Tainaka, Katsuhiko Matsumoto, Yuta Shinohara, Koji L. Ode, Etsuo A. Susaki, Hiroki R. Ueda

    PLOS ONE   9 ( 3 )   e92369   2014年3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:PUBLIC LIBRARY SCIENCE  

    DNA can be concatenated by hybridization of DNA fragments with protruding single-stranded termini. DNA cleavage occurring at a nucleotide containing a DNA base analogue is a useful method to obtain DNA with designed protruding termini. Here, we report a novel non-enzymatic DNA cleavage reaction for DNA concatenation. We found that DNA is cleaved at a nucleotide containing 5-ethynyluracil in a methylamine aqueous solution to generate 59-phosphorylated DNA fragment as a cleavage product. We demonstrated that the reaction can be applied to DNA concatenation of PCR-amplified DNA fragments. This novel non-enzymatic DNA cleavage reaction is a simple practical approach for DNA concatenation.

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  • Positional Effects of Phosphorylation on the Stability and Morphology of Tau-Related Amyloid Fibrils 査読

    Masafumi Inoue, Takashi Konno, Kazuki Tainaka, Eiji Nakata, Hiro-o Yoshida, Takashi Morii

    BIOCHEMISTRY   51 ( 7 )   1396 - 1406   2012年2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:AMER CHEMICAL SOC  

    Hyperphosphorylated forms of tau protein are the main component of paired helical filaments (PHFs) of neurofibrillary tangles in the brain of Alzheimer's disease patients. To understand the effect of phosphorylation on the fibrillation of tau, we utilized tau-derived phosphorylated peptides. The V(306)QIVYK(311) sequence (PHF6) in the microtubule-binding domain is known to play a key role in the fibrillation of tau, and the short peptide corresponding to the PHF6 sequence forms amyloid-type fibrils similar to those generated by full-length tau. We focused on the amino acid residue located at the N-terminus of the PHF6 sequence, serine or lysine in the native isoform of tau, and synthesized the PHF6 derivative peptides with serine or lysine at the N-terminus of PHF6. Peptides phosphorylated at serine and/or tyrosine were synthesized to mimic the possible phosphorylation at these positions. The critical concentrations of the fibrillation of peptides were determined to quantitatively assess fibril stability. The peptide with the net charge of near zero tended to form stable fibrils. Interestingly, the peptide phosphorylated at the N-terminal serine residue exhibited remarkably low fibrillation propensity as compared to the peptide possessing the same net charge. Transmission electron microscopy measurements of the fibrils visualized the paired helical or straight fibers and segregated masses of the fibers or heterogeneous rodlike fibers depending on the phosphorylation status. Further analyses of the fibrils by the X-ray fiber diffraction method and Fourier transform infrared spectroscopic measurements indicated that all the peptides shared a common cross-beta structure. In addition, the phosphoserine-containing peptides showed the characteristics of beta-sandwiches that could interact with both faces of the beta-sheet. On the basis of these observations, possible protofilament models with four beta-sheets were constructed to consider the positional effects of the serine and/or tyrosine phosphorylations. The electrostatic intersheet interaction between phosphate groups and the amino group of lysine enhanced the lateral association between beta-sheets to compensate for the excess charge. In addition to the previously postulated net charge of the peptide, the position of the charged residue plays a critical role in the amyloid fibrillation of tau.

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  • Generation of Singlet Oxygen during Photosensitized One-Electron Oxidation of DNA 査読

    Yasuko Osakada, Kiyohiko Kawai, Takashi Tachikawa, Mamoru Fujitsuka, Kazuki Tainaka, Shozo Tero-Kubota, Tetsuro Majima

    CHEMISTRY-A EUROPEAN JOURNAL   18 ( 4 )   1060 - 1063   2012年1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:WILEY-V C H VERLAG GMBH  

    DOI: 10.1002/chem.201101964

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  • ICON probes: synthesis and DNA methylation typing. 査読

    Tainaka K, Okamoto A

    Current Protocols in Nucleic Acid Chemistry   Chapter 8 ( 47 )   1 - 17   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/0471142700.nc0807s47

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  • Sequence Dependence of Excess Electron Transfer in DNA 査読

    Kazuki Tainaka, Mamoru Fujitsuka, Tadao Takada, Kiyohiko Kawai, Tetsuro Majima

    JOURNAL OF PHYSICAL CHEMISTRY B   114 ( 45 )   14657 - 14663   2010年11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:AMER CHEMICAL SOC  

    DNA-mediated charge transfer has recently received a substantial attention because of its biological relevance in the DNA damage and DNA repair as well as the potential applications to nanoscale electronic devices In contrast to the numerous mechanistic studies on oxidative hole transfer (HT) through DNA our understanding of reductive electron transfer process still remains limited In this article, we demonstrate the results of direct observation of the excess electron transfer (EET) through DNA, which conjugated with aminopyrene ((A)Py) and diphenylacetylene (DPA) as a photosensitizing donor and an acceptor of excess electron, respectively By inserting dihydrothymine as a spacer between (A)Py and T or C, the yield of electron arrival to DPA was improved It was indicated that EET through DNA completed within a few or a few tens nanosecond time scale even for EET over 34 angstrom for both consecutive T and C sequences The various factors such as mismatch sequence and DNA length on the yield of electron arrival to DPA were examined

    DOI: 10.1021/jp1024685

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  • Design Strategies of Fluorescent Biosensors Based on Biological Macromolecular Receptors 査読

    Kazuki Tainaka, Reiko Sakaguchi, Hironori Hayashi, Shun Nakano, Fong Fong Liew, Takashi Morii

    SENSORS   10 ( 2 )   1355 - 1376   2010年2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:MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI  

    Fluorescent biosensors to detect the bona fide events of biologically important molecules in living cells are increasingly demanded in the field of molecular cell biology. Recent advances in the development of fluorescent biosensors have made an outstanding contribution to elucidating not only the roles of individual biomolecules, but also the dynamic intracellular relationships between these molecules. However, rational design strategies of fluorescent biosensors are not as mature as they look. An insatiable request for the establishment of a more universal and versatile strategy continues to provide an attractive alternative, so-called modular strategy, which permits facile preparation of biosensors with tailored characteristics by a simple combination of a receptor and a signal transducer. This review describes an overview of the progress in design strategies of fluorescent biosensors, such as auto-fluorescent protein-based biosensors, protein-based biosensors covalently modified with synthetic fluorophores, and signaling aptamers, and highlights the insight into how a given receptor is converted to a fluorescent biosensor. Furthermore, we will demonstrate a significance of the modular strategy for the sensor design.

    DOI: 10.3390/s100201355

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  • Construction of the Artificial Enzyme for Using Solar Energy 査読

    Shun Nakano, Masatora Fukuda, Kazuki Tainaka, Takashi Morii

    Green Energy and Technology   44   176 - 180   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We have recently introduced novel methods for constructing a wide variety of ligand-binding receptors and fluorescent biosensors based on a framework of ribonucleopeptide (RNP) composed of an RNA subunit and a peptide subunit. The modular RNP complex would be potentially applicable to the fabrication of the artificial enzyme because each subunit could be functionalized separately. In this study, we focused on the material conversion process in the photosynthesis and aimed at the development of the artificial photodriven enzymes based on the RNP complex. The strict control of the configuration and orientation of functionalized motifs is needed for the rational design of the RNP-based enzyme. To clarify the relationship between the structure and the function of RNP receptor, secondary structure of the ATP-binding RNP receptor was investigated. As a result, the model for the ATP-binding RNP complex could be proposed based on the chemical structure analyses. © Springer 2010.

    DOI: 10.1007/978-4-431-99779-5_27

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  • An In Vivo Fluorescent Sensor Reveals Intracellular Ins(1,3,4,5)P-4 Dynamics in Single Cells 査読

    Reiko Sakaguchi, Kazuki Tainaka, Naoko Shimada, Shun Nakano, Masafumi Inoue, Shigeki Kiyonaka, Yasuo Mori, Takashi Morii

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   49 ( 12 )   2150 - 2153   2010年

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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:WILEY-V C H VERLAG GMBH  

    DOI: 10.1002/anie.200903951

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  • A single circularly permuted GFP sensor for inositol-1,3,4,5-tetrakisphosphate based on a split PH domain 査読

    Reiko Sakaguchi, Takashi Endoh, Seigo Yamamoto, Kazuki Tainaka, Kenji Sugimoto, Nobutaka Fujieda, Shigeki Kiyonaka, Yasuo Mori, Takashi Morii

    BIOORGANIC & MEDICINAL CHEMISTRY   17 ( 20 )   7381 - 7386   2009年10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:PERGAMON-ELSEVIER SCIENCE LTD  

    A fluorescent sensor for the detection of inositol-1,3,4,5-tetrakisphosphate, Ins(1,3,4,5)P(4), was constructed from a split PH domain and a single circularly permuted GFP. A structure-based design was conducted to transduce a ligand-induced subtle structural perturbation of the split PH domain to an alteration in the population of the protonated and the deprotonated states of the GFP chromophore. Excitation of each distinct absorption band corresponding to the protonated or the deprotonated state of GFP resulted an increase and a decrease, respectively, in the intensity of emission spectra upon addition of Ins(1,3,4,5)P(4) to the split PH domain-based sensor. The Ins(1,3,4,5)P(4) sensor retained the ligand affinity and the selectivity of the parent PH domain, and realized the ratiometric fluorescence detection of Ins(1,3,4,5)P(4). (c) 2009 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmc.2009.08.015

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  • Osmium Complexation of Mismatched DNA: Effect of the Bases Adjacent to Mismatched 5-Methylcytosine 査読

    Akiko Nomura, Kazuki Tainaka, Akimitsu Okamoto

    BIOCONJUGATE CHEMISTRY   20 ( 3 )   603 - 607   2009年3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:AMER CHEMICAL SOC  

    The efficiency of osmium complex formation at 5-methylcytosine in mismatched DNA duplexes is a key point for the design of sequence-specific detection of DNA methylation. Osmium complexation was not observed in fully matched duplexes, whereas the complexation site and efficiency in mismatched duplexes changed depending on the type of 5&apos;-neighboring base of the 5-methylcytosine forming a mismatched base pair. In particular, when the base adjacent to the 5&apos; side of the mismatched base pair was thymine, a unique "side reaction" was observed. However, the nature of the mismatched base pairs in the reaction site did not influence the selectivity of osmium complex formation with methylated DNA.

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  • Osmium complex binding to mismatched methylcytosine: effect of adjacent bases. 査読

    Nomura A, Tainaka K, Okamoto A

    Nucleic acids symposium series (2004)   ( 53 )   207 - 208   2009年

  • 2TA1-06 タウ由来ペプチドの繊維性凝集におけるリン酸化の部位的効果(蛋白質-物性(安定性,折れたたみなど),第47回日本生物物理学会年会)

    Konno Takashi, Inoue Masafumi, Tainaka Kazuki, Morii Takashi

    生物物理   49   S39   2009年

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    記述言語:英語   出版者・発行元:一般社団法人 日本生物物理学会  

    DOI: 10.2142/biophys.49.S39_5

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  • The amyloid fibrillization of phosphorylated human tau core peptides

    Inoue Masafumi, Tainaka Kazuki, Hirata Akiyoshi, Konno Takashi, Morii Takashi

    Transactions of the Materials Research Society of Japan   34 ( 3 )   517 - 520   2009年

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    記述言語:英語   出版者・発行元:The Materials Research Society of Japan  

    Post-translational phosphorylation of the microtubule-associated protein tau is believed to have close relevance to the pathogenesis of Alzheimers disease. The growth of amyloid fibrils of the short peptide segment VQIVY<sub>310</sub>K (PHF6) corresponding to the core part of tau fibril formation is strongly affected by the phospholylation at Tyr310 via its electrostatic pairing with the neighboring charged lysine. Herein, we studied the propensity of resultant fibrils from PHF6 derivative peptides with charged aromatic amino acid residue at Tyr310. The results showed that the phosphorylation at Tyr310 contributed to significant enhancement of the amyloidogenicity and the stability of fibrillar aggregates. The physical origin of remarkable stabilization of fibrils by tyrosine phosphorylation is plausibly attributed to the charge pairing with the adjacent lysine residue in a similar fashion to the phosphorylation effect on the growth of amyloid fibril.

    DOI: 10.14723/tmrsj.34.517

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  • Charge-Pairing Mechanism of Phosphorylation Effect upon Amyloid Fibrillation of Human Tau Core Peptide 査読

    Masafumi Inoue, Akiyoshi Hirata, Kazuki Tainaka, Takashi Morii, Takashi Konno

    BIOCHEMISTRY   47 ( 45 )   11847 - 11857   2008年11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:AMER CHEMICAL SOC  

    Phosphorylation of a fibrillogenic protein, human tau, is believed to play crucial roles in the pathogenesis of Alzheimer&apos;s disease. For elucidating molecular mechanisms of the phosphorylation effect on tau fibrillation, we synthesized a peptide, VQTVY(310)K (PHF6) and its phosphorylated derivative (PHF(6)pY). PHF6 is a partial peptide surrounding a plausible in vivo phosphorylation site Tyr310 and forms amyloid-type fibrils similar to those generated by full-length tau. Fibrillation of PHF6 and PHF6pY were studied by spectroscopic and microscopic methods, and the critical concentration of the fibrillation was determined for comparing the fibril stability. The results showed that the phosphorylation strongly influenced the fibrillation propensity of PHF6 by changing its dependency on pH and ionic strength. On the basis of the observations, we suggested that charged sites on the phosphate group and its electrostatic pairing with the neighboring charged residues were physical origins of the phosphorylation effect. To verify this charge-pairing mechanism, we conducted experiments using a series of PHF6 derivatives with non-native charge distributions. The electrostatic interaction in an intermolecular mode was also demonstrated by the system composed of two different peptide species, which found that fibrillation of nonphosphorylated PHF6 was drastically enhanced when a trace amount of phosphorylated PHF6 molecules coexisted. A simulation analysis utilizing crystal coordinates of the PHF6 fibril was also performed for interpreting the experimental results in a molecular level. The present study using the model peptide system gave us a microscopically insightful view on the roles of tau phosphorylation in amyloid-related diseases.

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  • Synthesis of bipyridine-adenine conjugates for DNA methylation analysis 査読

    Tainaka Kazuki, Okamoto Akimitsu

    Chemistry of Nucleic Acid Components   10   146 - 149   2008年

  • An Osmium-DNA interstrand complex: Application to facile DNA methylation analysis 査読

    Kazuo Tanaka, Kazuki Tainaka, Tadashi Umemoto, Akiko Nomura, Akimitsu Okamoto

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   129 ( 46 )   14511 - 14517   2007年11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:AMER CHEMICAL SOC  

    Nucleic acids often acquire new functions by forming a variety of complexes with metal ions. Osmium, in an oxidized state, also reacts with C5-methylated pyrimidines. However, control of the sequence specificity of osmium complexation with DNA is still immature, and the value of the resulting complexes is unknown. We have designed a bipyridine-attached adenine derivative for sequence-specific osmium complexation. Sequence-specific osmium complexation was achieved by hybridization of a short DNA molecule containing this functional nucleotide to a target DNA sequence and resulted in the formation of a cross-linked structure. The interstrand cross-link clearly distinguished methylated cytosines from unmethylated cytosines and was used to quantify the degree of methylation at a specific cytosine in the genome.

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  • Direct labeling of 5-methylcytosine and its applications 査読

    Kazuo Tanaka, Kazuki Tainaka, Taku Kamei, Akimitsu Okamoto

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   129 ( 17 )   5612 - 5620   2007年5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:AMER CHEMICAL SOC  

    Cytosine methylation is one of the most important epigenetic events, and much effort has been directed to develop a simple reaction for methylcytosine detection. In this paper, we describe the design of tag-attachable ligands for direct methylcytosine labeling and their application to fluorescent and electrochemical assays. The effect of the location of bipyridine substituents on the efficiency of osmium complexation at methylcytosine was initially investigated. As a result, a bipyridine derivative with a substituent at the C4 position showed efficient complexation at the methylcytosine residue of single-stranded DNA in a reaction mixture containing potassium osmate and potassium hexacyanoferrate(III). On the basis of this result, a bipyridine derivative with a tag-attachable amino linker at the C4 position was synthesized. The efficiency of metal complex formation in the presence of the osmate and the synthetic ligand was clearly changed by the presence/absence of a methyl group at the C5 position of cytosine. The succinimidyl esters of functional labeling units were then attached to the bipyridine ligand fixed on the methylcytosine. These labels attached to methylcytosine enabled us to detect the target methylcytosine in DNA both fluorometrically and electrochemically. For example, we were able to fluorometrically obtain information on the methylation status at a specific site by means of fluorescence resonance energy transfer from a hybridized fluorescent DNA probe to a fluorescent label on methylcytosine. In addition, by the combination of electrochemically labeled methylcytosine and an electrode modified by probe DNAs, a methylcytosine-selective characteristic current signal was observed. This direct labeling of methylcytosine is a conceptually new methylation detection assay with many merits different from conventional assays.

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  • Synthesis and fluorescence properties of dimethylaminonaphthalene-deoxyuridine conjugates as polarity-sensitive probes 査読

    Akimitsu Okamoto, Kazuki Tainaka, Tomo Unzai, Isao Saito

    TETRAHEDRON   63 ( 17 )   3465 - 3470   2007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:PERGAMON-ELSEVIER SCIENCE LTD  

    The design of probes for monitoring various structures and dynamics of DNA and its surroundings is an important step in understanding biological events accompanying interbiomolecular interaction. We have developed novel fluorescent nucleosides in which the uracil base and the fluorophore are tethered by rigid linkers. They show unique absorption and fluorescence emission spectra. Nucleoside 2 is a fluorophore with high CT character and the fluorescence is very sensitive to solvent polarity. Nucleoside 3 shows absorption and emission maxima with longer wavelength due to extension of the DAN-conjugate system. These fluorophore-deoxyuridine conjugates with unique fluorescence properties would work as reporter probes sensitive to the change in microenvironment around specific sites of DNA. (c) 2007 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tet.2006.09.113

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  • PRODAN-conjugated DNA: Synthesis and photochemical properties 査読

    Kazuki Tainaka, Kazuo Tanaka, Shuji Ikeda, Ken-ichiro Nishiza, Tomo Unzai, Yoshimasa Fujiwara, Isao Saito, Akimitsu Okamoto

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   129 ( 15 )   4776 - 4784   2007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:AMER CHEMICAL SOC  

    A solvatochromic fluorophore, PRODAN, has been used as a microenvironment-sensitive reporter. Based on the chemistry of PRODAN, we designed and synthesized four novel fluorescent nucleosides, X-PDN (X = U, C, A, and G), to which a PRODAN fluorophore was attached at pyrimidine C5 or purine C8. The fluorescent nucleosides sensitively varied the Stokes shift values depending on the orientational polarizability of the solvent. The X-PDN incorporated into DNA also changed the Stokes shift values depending on the DNA structure. In particular, the excitation spectrum of the X-PDN-containing duplex shifted to a longer wavelength and gave a smaller Stokes shift value when the base opposite X-PDN could form a Watson-Crick base pair with X-PDN. A lower energy excitation of X-PDN-containing DNA resulted in a strong fluorescence emission selective to the Watson-Crick pairing base. This unique photochemical character was applicable to the efficient typing of single-nucleotide polymorphisms of genes.

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  • Methylcytosine-selective fluorescence quenching by osmium complexation 査読

    Kazuo Tanaka, Kazuki Tainaka, Akimitsu Okamoto

    BIOORGANIC & MEDICINAL CHEMISTRY   15 ( 4 )   1615 - 1621   2007年2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:PERGAMON-ELSEVIER SCIENCE LTD  

    We report on the control of the emission from a fluorophore fixed on DNA using the methylcytosine-selective addition of an osmium-bipyridine complex. We have synthesized DNA modified by a microenvironment-sensitive fluorophore, 2-dimethylamino-6-acyl-naphthalene. The emission from the fluorophore tethered to a probe DNA was effectively quenched by a methylcytosine glycol-osmium-bipyridine triad, which was located in the immediate neighborhood of the fluorophore. The discrimination of the cytosine methylation status at a methylation hot spot in the p53 gene was also executed using a well-designed fluorescent DNA probe. (c) 2006 Elsevier Ltd. All rights reserved.

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  • Selective oxidation of methylcytosine in single base pair mismatches by osmium complex. 査読

    Nomura A, Tainaka K, Okamoto A

    Nucleic acids symposium series (2004)   ( 51 )   299 - 300   2007年

  • Chemistry of osmium-DNA complexes. 査読

    Umemoto T, Tainaka K, Tanaka K, Okamoto A

    Nucleic acids symposium series (2004)   ( 51 )   175 - 176   2007年

  • DNA methylation analysis using metal complex formation. 査読

    Okamoto A, Tanaka K, Tainaka K, Umemoto T, Nomura A

    Nucleic acids symposium series (2004)   ( 51 )   27 - 28   2007年

  • Nile Red nucleoside: Design of a solvatofluorochromic nucleoside as an indicator of micropolarity around DNA 査読

    A Okamoto, K Tainaka, Y Fujiwara

    JOURNAL OF ORGANIC CHEMISTRY   71 ( 9 )   3592 - 3598   2006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:AMER CHEMICAL SOC  

    The fluorophore, Nile Red, effectively works as a polarity-sensitive fluorescence probe. We have designed a new nucleoside modified by Nile Red for examining the change in the polarity of the microenvironment surrounding DNA. We synthesized a Nile Red nucleoside (1), formed by replacing nucleobases with Nile Red, through the coupling of a 2-hydroxylated Nile Red derivative and 1,2-dideoxyglycan. This nucleoside showed a high solvatofluorochromicity. The fluorescence of 1 incorporated into DNA was greatly shifted to shorter wavelength by the addition of beta-cyclodextrin. The photophysical function of the Nile Red nucleoside will be a good optical indicator for monitoring the change in the micropolarity properties at a specific site on target sequences with interaction between DNA and DNA-binding molecules.

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  • Simple SNP typing assay using a base-discriminating fluorescent probe 査読

    A Okamoto, K Tainaka, Y Ochi, K Kanatani, Saito, I

    MOLECULAR BIOSYSTEMS   2 ( 2 )   122 - 126   2006年2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:ROYAL SOC CHEMISTRY  

    We have developed a new concept involving a single-step homogeneous method for single-nucleotide polymorphism (SNP) typing. in this method, a probe containing base-discriminating fluorescent (BDF) bases is added to a sample solution. BDF base-containing DNA usually shows only a weak fluorescence, but emits a strong blue fluorescence when it recognizes a target base at a specific site in a hybridized strand. By utilizing this feature, a simple mix-and-read SNP typing assay was achieved without any tedious probe-designing or washing processes for exclusion of hybridization error or any addition of DNA-modifying enzymes. This is very different from conventional methods. We simultaneously analyzed a number of samples with ease, with a high accuracy, using our BDF assay.

    DOI: 10.1039/b515923g

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  • Synthesis and properties of novel PRODAN-labeled uridine. 査読

    Tainaka K, Ikeda S, Tanaka K, Nishiza K, Unzai T, Okamoto A, Saito I

    Nucleic acids symposium series (2004)   ( 50 )   131 - 132   2006年

  • Development of bipyridine-modified nucleobase for methylcytosine-selective crosslink reaction. 査読

    Tainaka K, Tanaka K, Okamoto A

    Nucleic acids symposium series (2004)   ( 50 )   129 - 130   2006年

  • Photochemical evaluation of dual fluorescence of a novel DNA groove binder. 査読

    Tanaka K, Tainaka K, Fujishima S, Okamoto A

    Nucleic acids symposium series (2004)   ( 50 )   137 - 138   2006年

  • Fluorescence quenching by methylcytosine-metal complexation. 査読

    Tanaka K, Tainaka K, Okamoto A

    Nucleic acids symposium series (2004)   ( 50 )   139 - 140   2006年

  • Development of novel PRODAN-labeled nucleosides as base-discriminating fluorescent probes. 査読

    Tainaka K, Ikeda S, Tanaka K, Nishiza K, Fujiwara Y, Okamoto A, Saito I

    Nucleic acids symposium series (2004)   ( 50 )   133 - 134   2006年

  • Development of fluorescence-labeling method for methylcytosine with metal complexation. 査読

    Tanaka K, Tainaka K, Kamei T, Okamoto A

    Nucleic acids symposium series (2004)   ( 50 )   135 - 136   2006年

  • Development of electrochemical detection for methylcytosine and its application. 査読

    Tanaka K, Tainaka K, Kamei T, Okamoto A

    Nucleic acids symposium series (2004)   ( 50 )   141 - 142   2006年

  • Luminescence properties of dual fluorescent pyrene derivatives used as DNA probe molecule. 査読

    Kodate S, Wada H, Suzuka I, Okamoto A, Tainaka K, Saito Y, Saito I

    Nucleic acids symposium series (2004)   ( 50 )   211 - 212   2006年

  • Sequence-selective osmium oxidation of DNA: efficient distinction between 5-methylcytosine and cytosine 査読

    A Okamoto, K Tainaka, T Kamei

    ORGANIC & BIOMOLECULAR CHEMISTRY   4 ( 9 )   1638 - 1640   2006年

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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:ROYAL SOC CHEMISTRY  

    5-Methylcytosine was distinguished from cytosine using the large difference of their osmium oxidation rates, and this reaction was applied to detection of the cytosine methylation status at a specific site of a long sequence using the formation of a bulge structure by hybridization with a guide DNA.

    DOI: 10.1039/b600401f

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  • A dielectric-sensitive fluorescent DNA probe for monitoring polarities on the interior of a DNA-binding protein 査読

    A Okamoto, K Tainaka, Saito, I

    BIOCONJUGATE CHEMISTRY   16 ( 5 )   1105 - 1111   2005年9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:AMER CHEMICAL SOC  

    We report a novel fluorescent nucleobase, U-DNC, for the mapping of the local dielectric properties around DNA. Fluorescence spectra of the nucleoside d U-DNC showed a significant shift depending on the solvent polarity. This property was used to determine the dielectric constants of the interior of DNA-binding proteins, such as DNA polymerases. We were able to demonstrate that the DNA-binding region of the Klenow fragment is a lower polarity site, as shown by the blue shift of the fluorescence peak originating from U-DNC.

    DOI: 10.1021/bc050077i

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  • Monitoring DNA structures by dual fluorescence of pyrene derivatives 査読

    A Okamoto, K Tainaka, K Nishiza, Saito, I

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   127 ( 38 )   13128 - 13129   2005年9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:AMER CHEMICAL SOC  

    DOI: 10.1021/ja053609e

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  • Design of highly selective fluorescent nucleobases for SNP typing: Base-discriminating fluorescent (BDF) probe 査読

    Saito, I, Y Saito, A Okamoto, T Ichiba, K Kanatani, K Tainaka

    Chemistry of Nucleic Acid Components   7   57 - 64   2005年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:ACAD SCI CZECH REPUBLIC, INST ORGANIC CHEM & BIOCHEMISTRY  

    We designed a new type of pyrene-labeled base-discrimination fluorescent (BDF) nucleosides U-PY, C-PY, (8PY)A and (MePY)dA, which emitted strong florescence only when the bases opposite the BDF bases are A, G, T and C, respectively. The DNA probes containing four different BDF bases enabled us to distinguish single base alterations by simply mixing with a sample solution of target DNA. A example of SNP typing of c-Ha-ras SNP sequence has been demonstrated. Detection of base insertion in indel polymorphisms using pyrene excimer fluorescent probe has also been described.

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  • SNPs typing by base-discriminating fluorescence DNA probe. 査読

    Okamoto A, Tainaka K, Ochi Y, Saito I

    Nucleic acids symposium series (2004)   ( 49 )   201 - 202   2005年

  • Nile Red nucleoside: novel nucleoside analog with a fluorophore replacing the DNA base. 査読

    Tainaka K, Fujiwara Y, Okamoto A

    Nucleic acids symposium series (2004)   ( 49 )   155 - 156   2005年

  • Sequence-selective 5-methylcytosine oxidation for epigenotyping. 査読

    Okamoto A, Tainaka K

    Nucleic acids symposium series (2004)   ( 49 )   45 - 46   2005年

  • Development of a novel solvatochromic pyrimidine analog for probing local dielectric environment of DNA polymerase. 査読

    Tainaka K, Okamoto A, Saito I

    Nucleic acids symposium series (2004)   ( 48 )   31 - 32   2004年

  • Synthesis and properties of a novel fluorescent nucleobase, naphthopyridopyrimidine 査読

    A Okamoto, K Tainaka, Saito, I

    TETRAHEDRON LETTERS   44 ( 36 )   6871 - 6874   2003年9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:PERGAMON-ELSEVIER SCIENCE LTD  

    A new base-discriminating fluorescent nucleoside, NPP, that can sharply distinguish between A and G bases opposite NPP is described. The hybridization of an ODN probe containing NPP with a target DNA facilitates the judgment of the type of purine base located at a specific site on the target DNA. (C) 2003 Published by Elsevier Ltd.

    DOI: 10.1016/S0040-4039(03)01740-4

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  • Detection of A/G single nucleotide alteration in RNA using base-discriminating fluorescent oligodeoxynucleotides 査読

    A Okamoto, K Tainaka, Saito, I

    CHEMISTRY LETTERS   32 ( 8 )   684 - 685   2003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:CHEMICAL SOC JAPAN  

    We report the fluorescence properties of oligodeoxynucleotides (ODNs) containing a base-discriminating fluorescent nucleoside, benzopyridopyrimidine (BPP), in hybridizing with RNAs possessing different bases opposite BPP. BPP-containing ODN selectively exhibited a strong fluorescence when the RNA base opposite BPP was A, whereas the fluorescence of BPP-containing ODN hybridized with RNA possessing G opposite BPP was very weak. BPP acts as a good base-discriminating fluorescent nucleoside for A/G single base alteration of RNA.

    DOI: 10.1246/cl.2003.684

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  • Clear distinction of purine bases on the complementary strand by a fluorescence change of a novel fluorescent nucleoside 査読

    A Okamoto, K Tainaka, Saito, I

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   125 ( 17 )   4972 - 4973   2003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:AMER CHEMICAL SOC  

    DOI: 10.1021/ja034090u

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  • Oligonucleotides containing 7-vinyl-7-deazaguanine as a facile strategy for expanding the functional diversity of DNA 査読

    A Okamoto, T Taiji, K Tainaka, Saito, I

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   12 ( 15 )   1895 - 1896   2002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:PERGAMON-ELSEVIER SCIENCE LTD  

    A modified nucleobase 7-vinyl-7-deazaguanine ((V)G) produced adducts with maleimides through Diels-Alder cycloaddition under very mild conditions. By this method, post-synthetic modification to oligonucleotides with diverse functionality (carboxylic acid, pyrene, benzophenone, succinimidyl ester, nitroxide and biotin) was accomplished. (C) 2002 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0960-894X(02)00334-7

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  • A facile incorporation of the aldehyde function into DNA: 3-Formylindole nucleoside as an aldehyde-containing universal nucleoside 査読

    Akimitsu Okamoto, Kazuki Tainaka, Isao Saito

    Tetrahedron Letters   43 ( 26 )   4581 - 4583   2002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)  

    The first facile incorporation of an aldehyde function into DNA without any protection/deprotection of the aldehyde was achieved by the use of 3-formylindole 2′-deoxynucleoside (1). This building block is very easily prepared and efficiently incorporated into oligonucleotides. In addition, 1 acted as a universal nucleoside in duplex. The post-synthetic modification of oligonucleotides bearing 1 with functionalized molecules was also effective. © 2002 Published by Elsevier Science Ltd.

    DOI: 10.1016/S0040-4039(02)00888-2

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MISC

  • 三次元病理解析に資する組織透明化手法の開発

    久保田晋平, 高橋恵生, 田井中一貴, 江幡正悟, 上田泰己, 宮園浩平

    日本病理学会会誌   110 ( 1 )   2021年

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  • 組織透明化によるがん転移解析基盤の確立

    久保田 晋平, 高橋 恵生, 西田 純, 江幡 正悟, 田井中 一貴, 上田 泰己, 宮園 浩平

    日本薬理学会年会要旨集   93 ( 0 )   1 - YIA-16   2020年

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    記述言語:日本語   出版者・発行元:公益社団法人 日本薬理学会  

    <p>It has been recognized that interactions between cancer cells and stroma are important for survival of cancer cells and metastasis at distant organs. In addition, the complexity within tumor microenvironment contributes to resistance of conventional therapy. Therefore, despite decades of cancer researches, it is still difficult to elucidate the complexity of tumor microenvironment at whole organ or whole body level. To understand tumor microenvironment and overcome cancer, it is necessary to detect and quantify sparsely distributed metastatic cells throughout the body or organ at single-cell resolution. </p><p>Here, we demonstrate that CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis)-based cancer (CUBIC-Cancer) analysis with refractive-indices (RI) optimized protocol enables comprehensive cancer cell profiling in whole body and organs. We applied CUBIC-Cancer analysis to a dozen mouse models using several cancer cells and spatio-temporal quantification of metastatic cancer progression at single-cell resolution. As a result, metastatic foci can be observed and quantified through whole organ or whole body at single-cell resolution. In addition, three-dimensional (3D) monitoring revealed that the patterns of metastasis were dependent upon cancer cell or metastatic organs. Comparing two cancer cell lines, we quantified the difference of metastatic processes between angiogenesis and vessel cooption. Whole-organ profiling with single-cell resolution also enables to quantify the early steps of lung metastasis formation and rejection.CUBIC-Cancer analysis suggests that the epithelial-mesenchymal transition promotes not only extravasation but also cell survival at metastatic sites. CUBIC-Cancer analysis is applicable to pharmacotherapeutic profiling of anti-tumor drugs. CUBIC-Cancer analysis is compatible with in vivo bioluminescence imaging and 2D histology.We suggest that a scalable analytical pipeline with these three modalities may contribute to addressing currently incurable metastatic diseases.</p>

    DOI: 10.1254/jpssuppl.93.0_1-YIA-16

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  • CUBIC-癌分析法を用いた癌転移の全身/全組織的特性解析(Whole-body/organ profiling of cancer metastasis with CUBIC-Cancer analysis)

    久保田 晋平, 高橋 恵生, 西田 純, 江幡 正悟, 田井中 一貴, 上田 泰己, 宮園 浩平

    生命科学系学会合同年次大会   2017年度   [2P - 1450]   2017年12月

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    記述言語:英語   出版者・発行元:生命科学系学会合同年次大会運営事務局  

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  • CUBIC-癌分析法を用いた癌転移の全身/全組織的特性解析(Whole-body/organ profiling of cancer metastasis with CUBIC-Cancer analysis)

    久保田 晋平, 高橋 恵生, 西田 純, 江幡 正悟, 田井中 一貴, 上田 泰己, 宮園 浩平

    生命科学系学会合同年次大会   2017年度   [2P - 1450]   2017年12月

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    記述言語:英語   出版者・発行元:生命科学系学会合同年次大会運営事務局  

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  • タンパク質可視化・制御の新技術 細胞局所から個体まで CUBIC 化学混合液を用いた単一細胞レベルでの全器官と全組織のイメージング法(CUBIC: whole-organ, whole-body imaging with single-cell resolution using chemical cocktails)

    田井中 一貴, 洲崎 悦生, 久保田 晋平, 上田 泰己

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [2S4 - 5]   2015年12月

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    記述言語:英語   出版者・発行元:(公社)日本生化学会  

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  • マウスの臓器・個体を丸ごと1細胞解像度でイメージングする新技術

    田井中一貴

    臨床免疫・アレルギー科   64 ( 3 )   281 - 284   2015年9月

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    記述言語:日本語  

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  • 1細胞解像度全身・組織丸ごとイメージング

    上田 泰己, 田井中 一貴

    日本免疫学会ニュースレター45号   22 - 23   2015年4月

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    記述言語:日本語  

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  • 次世代生物学の扉を開く一細胞解析法 1細胞解像度個体全身三次元イメージング

    久保田晋平, 田井中一貴, 上田泰己

    細胞工学   34 ( 3 )   278 - 282   2015年2月

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    記述言語:日本語  

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  • CUBICを用いた全身三次元病理解析

    須山 孟, 田井中 一貴, 上田 泰己

    心臓   47 ( 2 )   285 - 291   2015年

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    記述言語:日本語   出版者・発行元:公益財団法人 日本心臓財団  

    DOI: 10.11281/shinzo.47.285

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  • マウス全脳・全身を透明化し1細胞解像度で観察する新技術を開発:アミノアルコールを含む化合物カクテルと高速イメージング・画像解析を組み合わせた「CUBIC」技術を実現

    久野 朗広, 洲崎 悦生, 田井中 一貴, 上田 泰己

    化学と生物   53 ( 11 )   737 - 740   2015年

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    記述言語:日本語   出版者・発行元:公益社団法人 日本農芸化学会  

    DOI: 10.1271/kagakutoseibutsu.53.737

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  • 脳を透明化して観察するCUBIC法-透明化溶剤と画像解析による新技術

    田井中一貴, 洲崎悦生, 上田泰己

    化学   69 ( 10 )   24 - 27   2014年10月

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    記述言語:日本語  

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  • 全脳全細胞を観察対象とする新規技術CUBIC

    洲崎悦生, 田井中一貴, PERRIN Dimitri, 上田泰己

    日本薬理学会関東部会プログラム・要旨集   130th   50   2014年

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    記述言語:日本語  

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  • 生体組織透明化・脱色化試薬による一細胞解像度個体丸ごとイメージング技術の開発 2

    久保田晋平, 田井中一貴, 上田泰己

    日本薬理学会関東部会プログラム・要旨集   131st   67   2014年

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    記述言語:日本語  

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  • 生体組織透明化・脱色化試薬による一細胞解像度個体丸ごとイメージング技術の開発 1

    田井中一貴, 久保田晋平, 上田泰己

    日本薬理学会関東部会プログラム・要旨集   131st   66   2014年

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    記述言語:日本語  

    J-GLOBAL

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  • 全組織スキャンニングによるシステミックな3次元遺伝子発現プロファイリング

    洲崎悦生, 田井中一貴, 渡邉朋信, 清成寛, 阿部高也, 宮脇敦史, 今井猛, 上田泰己

    日本分子生物学会年会プログラム・要旨集(Web)   36th   3P-0737 (WEB ONLY)   2013年

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    記述言語:日本語  

    J-GLOBAL

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  • 概日時計におけるタンパク質リン酸化反応の意義

    中嶋正人, 小山洋平, 田井中一貴, 上田泰己

    時間生物学   17 ( 2 )   146   2011年11月

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    記述言語:日本語  

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  • Structural aspects of the fluorescence intensity changes of the ATP-binding ribonucleopeptide sensor

    Nakano, S, Mashima, T, Tainaka, K, Katahira, M, Morii, T

    The 37th International Symposium on Nucleic Acids Chemistry 2010,   2010年11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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  • 可視光照射により光電流応答を示すDNA自己組織化膜の作製 査読

    丹佳夫, 田井中一貴, 藤枝伸宇, 森井孝

    日本化学会第89春季年会,日本大学,2009.3.27-30   2009年

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    記述言語:日本語  

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  • 蛍光タンパク質をもとにしたイノシトール四リン酸センサーの設計 査読

    藤枝伸宇, 山本誠吾, 遠藤太志, 坂口怜子, 田井中一貴, 森井孝

    日本化学会第89春季年会,日本大学,2009.3.27-30   2009年

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  • Construction of a stable functional ribonucleopeptide complex by the covalent linking method. 査読

    M. Fukuda, S. Nakano, K. Tainaka, N. Fujieda, T. Morii

    Nucleic acids symposium series (2004)   ( 52 )   195 - 196   2008年

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    記述言語:英語  

    DOI: 10.1093/nass/nrn099

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  • Selective recognition of a tetra-amino-acid motif containing phosphorylated tyrosine residue by ribonucleopeptide. 査読

    S. Nakano, T. Hasegawa, M. Fukuda, N. Fujieda, K. Tainaka, T. Morii

    Nucleic acids symposium series (2004)   ( 52 )   199 - 200   2008年

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    記述言語:英語  

    DOI: 10.1093/nass/nrn101

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  • Development of ribonucleopeptide-based fluorescent sensors for biologically active amines based on the stepwise molding strategy. 査読

    K. Tainaka, T. Hasegawa, M. Fukuda, S. Nakano, N. Fujieda, T. Morii

    Nucleic acids symposium series (2004)   ( 52 )   201 - 202   2008年

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    記述言語:英語  

    DOI: 10.1093/nass/nrn102

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  • Highly Selective Fluorescent Nucleobases for Designing Base-Discriminating Fluorescence Probe.

    齋藤 烈, Saito, I, Saito, Y, Hanawa, K, Hayashi, K, Motegi, K, Bag, S. S, Dohno, C, Ichiba, T, Tainaka, K, Okamoto, A

    Pure. Appl. Chemistry,   78 ( 12 )   2305 - 2312   2006年

  • Effect of Single Nucleotide Alteration in Hybridized RNA on Fluorescence Intensity of Dimethylaminonaphthalene-labeled DNA.

    齋藤 烈, A. Okamoto, K. Tainaka, I. Saito

    Photomedicine & Photobiology   ( 28 )   31 - 32   2006年

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  • Development of novel modified nucleobases as a fluorescence probe for detection of single nucleotide polymorphisms.

    K Tainaka, A Okamoto, Saito, I

    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY   224   U33 - U33   2002年8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:AMER CHEMICAL SOC  

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  • DNAの一塩基変異検出法の最近の進歩

    齋藤 烈, 田井中一貴

    未来材料   ( 2 )   32 - 37   2002年2月

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講演・口頭発表等

  • CUBIC: Whole-organ, whole-body imaging with single-cell resolution using chemical cocktails

    Kazuki Tainaka

    リエゾンラボ炎症シンポジウム  2019年8月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 組織透明化による3D神経病理学 招待

    田井中 一貴

    第16回日本病理学会カンファレンス  2019年8月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • Comprehensive 3D Imaging by Tissue Clearing Technique CUBIC 国際会議

    Kazuki Tainaka

    Neuro2019  2019年7月 

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    記述言語:英語   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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  • 3D神経病理学に向けたホールマウント染色手法の開発

    田井中一貴, 齋藤理恵, 井上雅文, 柿田明美

    第60回日本神経病理学会総会学術研究会  2019年7月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • CUBIC: 組織透明化技術による3Dイメージング 招待

    田井中 一貴

    第60回新潟生化学懇話会  2019年7月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • CUBIC:生体組織透明化による包括的3Dイメージング技術 招待

    田井中 一貴

    第738回新潟医学会  2019年4月 

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    記述言語:日本語   会議種別:口頭発表(基調)  

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  • CUBIC: Whole-brain/body imaging with single-cell resolution using hydrophilic chemical cocktails 招待 国際会議

    田井中 一貴

    生物機能化学国際シンポジウム  2019年4月 

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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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  • CUBIC: Whole-brain/body imaging with single-cell resolution using hydrophilic chemical cocktails 招待 国際会議

    Kazuki Tainaka

    The 9th BRI International Symposium  2019年3月 

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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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  • 水溶性試薬による組織透明化の化学 招待

    田井中 一貴

    ERATO浜地プロジェクト:ニューロ分子技術講演会2019-1  2019年1月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • 組織透明化技術CUBICによる個体・臓器丸ごと3Dイメージング 招待

    田井中 一貴

    ChemBioレクチャー  2018年12月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • 組織透明化技術CUBIC による3D神経病理学 招待

    田井中 一貴

    第107回日本病理学会総会  2018年6月 

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    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(指名)  

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  • 組織透明化技術と包括的3Dイメージング 招待

    田井中 一貴

    イメージング技術の融合による医学・生命科学の新たな地平の開拓  2018年2月 

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    記述言語:日本語   会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • 生体組織透明化技術CUBIC 招待

    田井中 一貴

    第15回 新潟内耳疾患研究会  2017年7月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • 組織透明化技術と脳コネクトーム 招待

    田井中 一貴

    第47回新潟神経学夏期セミナー  2017年7月 

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    記述言語:日本語   会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • CUBIC:生体組織透明化による包括的3Dイメージング技術 招待

    田井中 一貴

    北海道大学遺伝子病制御研究所セミナー  2017年6月 

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    記述言語:日本語   会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • CUBIC: whole-organ, whole-body imaging with single-cell resolution using chemical cocktals. 招待 国際会議

    田井中 一貴

    BMB2015 Biochemistry and Molecular Biology in Kobe, Japan.  2015年12月 

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

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  • CUBIC: Whole-organ, whole-body imaging with single-cell resolution using hydrophilic chemical cocktails. 招待 国際会議

    田井中 一貴

    International Conference on Systems Biology of Human Disease 2015 in Heidelberg, German.  2015年7月 

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

    *Lecture of the Anne Heidenthal Prize for Fluorescence Research

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  • 生体組織透明化技術 CUBIC 招待

    田井中一貴

    バイオガレージセミナー「生体・組織イメージングの最先端」  2014年10月 

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    記述言語:日本語   会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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産業財産権

  • 光透過性に優れた生物材料を調製するための組成物およびその利用(国内出願)

    上田泰己, 田井中一貴, 村上達哉

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    出願番号:特願2016-092025  出願日:2016年4月

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  • 光透過性に優れた生物材料を調製するための組成物およびその利用(国内出願)

    洲崎悦生, 田井中一貴, 上田泰己

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    出願番号:特願2013-168705  出願日:2013年8月

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  • 非天然型塩基を含むオリゴデオキシヌクレオチドの切断による5’末端リン酸化オリゴデオキシヌクレオチドの製造方法(PCT出願)

    上田泰己, 池田修二, 田井中一貴

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    出願番号:PCT/JP2013/058349  出願日:2013年3月

    公開番号:WO2013150902 A1  公開日:2013年10月

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  • 非天然型塩基を含むオリゴデオキシヌクレオチドの切断による5’末端リン酸化オリゴデオキシヌクレオチドの製造方法(国内出願)

    上田泰己, 池田修二, 田井中一貴

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    出願番号:特願2012-084249  出願日:2012年4月

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  • メチルシトシンの簡便検出法(PCT出願)

    岡本晃充, 田井中一貴, 田中一生, 亀井琢

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    出願番号:PCT/JP2006/306359  出願日:2006年3月

    公開番号:WO2006132022 A1  公開日:2006年12月

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  • プロダン含有ヌクレオシド及びその応用(国内出願)

    岡本晃充, 田井中一貴, 齋藤 烈, 高橋則彦

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    出願番号:特願2005-335005  出願日:2005年11月

    公開番号:特開2006-169240  公開日:2006年6月

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  • プロダン含有ヌクレオシド及びその応用(PCT出願)

    岡本晃充, 田井中一貴, 齋藤 烈, 高橋則彦

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    出願番号:US 11/135,368  出願日:2005年5月

    公開番号:US20060142311 A1  公開日:2006年6月

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  • ポリヌクレオチド誘導体およびその利用

    齋藤 烈, 岡本晃充, 田井中一貴, 飯田 満, 加藤輝久

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    出願番号:特願2002-333326  出願日:2002年11月

    公開番号:特開2004-168672  公開日:2004年6月

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  • メチルシトシンの簡便検出法(国内出願)

    岡本晃充, 田井中一貴, 田中一生, 亀井琢

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    出願番号:特願2007-520033 

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  • 光透過性に優れた生物材料を調製するための組成物およびその利用(PCT出願)

    洲崎悦生, 田井中一貴, 上田泰己

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    出願番号:PCT/JP2014/070618 

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受賞

  • 第58回日本神経病理学会総会学術研究会 優秀ポスター賞

    2017年6月  

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  • Anne Heidenthal Prize for Fluorescence Research at International Conference on Systems Biology of Human Disease 2015

    2015年7月  

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  • 日本化学会第88春季年会 優秀講演賞

    2008年3月  

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  • 日本化学会第84春季年会 学生講演賞

    2004年3月  

    田井中 一貴

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共同研究・競争的資金等の研究

  • 慢性ストレスによる心不全の分子病態解明に関する研究

    2019年10月 - 2022年3月

    国立研究開発法人日本医療研究開発機構  循環器病の予防法・治療法開発のための分子病態解明に関する研究 

    村上 正晃

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    資金種別:競争的資金

    Grant no. 19ek0210125h0001

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  • デジタル3D神経病理学の創成

    2019年8月 - 2022年3月

    文部科学省  挑戦的研究(開拓) 

    柿田 明美

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    資金種別:競争的資金

    Grant no. 19H05559

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  • てんかん原性病巣の病態機序と制御:外科標本のイメージングプラクティス

    2019年4月 - 2022年3月

    文部科学省  基盤研究(A) 

    柿田 明美

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    資金種別:競争的資金

    Grant no. 19H01061

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  • 脳小血管病の3D病理解析基盤の確立

    2018年7月 - 2019年3月

    文部科学省  挑戦的研究(萌芽) 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

    Grant no. 18K19373

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  • ヒト脳組織特異的染色による先進的3D神経病理学の確立

    2018年4月 - 2022年3月

    文部科学省  基盤研究(B) 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

    Grant no. 18H02105

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  • D1/D2ドーパミン受容体発現操作マウスによる運動制御と学習記憶機構の理解

    2018年4月 - 2021年3月

    文部科学省  基盤研究(B) 

    笹岡 俊邦

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    資金種別:競争的資金

    Grant no. 18H02540

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  • 組織夾雑系の理解を目的としたケミカルプローブの設計戦略

    2018年4月 - 2020年3月

    文部科学省  新学術領域研究(研究領域提案型) 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

    分子夾雑の生命化学, Grant no. 18H04543

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  • ヒト脳組織膨潤・透明化技術による神経病理学的解析

    2018年

    公益財団法人武田科学振興財団  2018年度医学系研究助成(精神・神経・脳領域) 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

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  • ゲートウェイ反射に基づく病原体侵入口形成機構の解明

    2017年8月 - 2020年3月

    国立研究開発法人日本医療研究開発機構  感染症研究革新イニシアティブ(J-PRIDE) 

    村上 正晃

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    資金種別:競争的資金

    Grant no. JP17fm0208023

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  • 3D免疫染色によるタンパク質の老化基盤の解析

    2017年4月 - 2019年3月

    文部科学省  新学術領域研究(研究領域提案型) 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

    脳タンパク質老化と認知症制御, Grant no. 17H05688

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  • ヒト脳組織特異的染色に向けたケミカルプローブの包括的プロファイリング

    2017年

    公益財団法人ノバルティス科学振興財団  2017年度研究奨励金 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

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  • 3D神経病理学に向けた組織透明化技術の開発

    2017年

    公益財団法人内藤記念科学振興財団  2017年度 内藤記念科学奨励金・研究助成 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

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  • 3 次元神経病理学の基盤となる染色技術の開発

    2017年

    公益財団法人東京生化学会  平成29年度 研究奨励金(II) 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

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  • 3Dイメージングによる脳小血管病の病態解析

    2017年

    公益財団法人細胞科学研究財団  平成30年度研究助成 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

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  • 細胞機能の変容により曝露物質の毒性を評価する新規安全性試験技術の開発

    2016年4月 - 2018年3月

    文部科学省  挑戦的萌芽研究 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

    Grant no. 16K15124

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  • 全身・臓器丸ごとイメージング技術によるバイオ医薬品の時間的・空間的な体内動態可視化技術の開発

    2015年10月 - 2016年12月

    国立研究開発法人日本医療研究開発機構  革新的バイオ医薬品創出基盤技術開発事業 

    上田 泰己

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    資金種別:競争的資金

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  • 全脳イメージング技術を用いた統合失調症治療薬投与時の脳内神経活動変化解析

    2015年

    公益財団法人薬理研究会  平成27年度研究助成 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

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  • 全身丸ごとイメージング技術を用いた炎症制御機構の解析基盤の確立

    2015年

    一般財団法人東京医学会  平成27年度医学研究助成 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

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  • 哺乳類概日振動体の構成的な理解

    2013年4月 - 2016年12月

    日本学術振興会  科学研究費補助金(基盤研究(S)) 

    上田 泰己

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    資金種別:競争的資金

    Grant no. 25221004

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  • プロドラッグを利用した細胞ネットワークにおける薬理活性評価システムの開発

    2013年

    一般財団法人島原科学振興会  平成25年度研究助成 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

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  • 可視光照射により酸化反応を触媒する太陽光駆動型オキシダーゼの開発

    2010年4月 - 2013年3月

    日本学術振興会  科学研究費補助金(若手研究(B)) 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

    Grant no. 22750152

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  • 太陽光駆動型人工酵素の作製

    2010年

    公益財団法人国際科学技術財団  2010年研究助成 

    田井中 一貴

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    担当区分:研究代表者  資金種別:競争的資金

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  • Development of the light-driven artificial reductase

    2008年 - 2013年

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    資金種別:競争的資金

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