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174 results on '"Kimura, Yasuhisa"'

1. Exploring bat-inspired cyclic tryptophan diketopiperazines as ABCB1 Inhibitors

Author

Koh, Javier Yu Peng, Itahana, Yoko, Krah, Alexander, Mostafa, Habib, Ong, Mingmin, Iwamura, Sahana, Vincent, Dona Mariya, Radha Krishnan, Sabhashina, Ye, Weiying, Yim, Pierre Wing Chi, Khopade, Tushar M., Chen, Kunihiko, Kong, Pui San, Wang, Lin-Fa, Bates, Roderick W., Kimura, Yasuhisa, Viswanathan, Rajesh, Bond, Peter J., and Itahana, Koji

Published
2024
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2. The ATPase activity of ABCA1 is increased by cholesterol in the presence of anionic lipids.

Author

Sakata, Kazuki, Kioka, Noriyuki, Ueda, Kazumitsu, and Kimura, Yasuhisa

Subjects
ATP-binding cassette transporters, ADENOSINE triphosphatase, CHOLESTEROL, LIPIDS, APOLIPOPROTEIN A, HIGH density lipoproteins
Abstract

High-density lipoprotein (HDL) transports excess cholesterol from peripheral tissues back to the liver, and plasma HDL levels are inversely related to cardiovascular disease incidence. ATP-binding cassette A1 (ABCA1) is a member of the ABC protein superfamily, and generates nascent HDL, which consists of several hundreds of phospholipids and cholesterol wrapped by apolipoprotein A-I (apoA-I). However, it remains unclear whether cholesterol is a transport substrate of ABCA1. Since ATP hydrolysis of ABC proteins is typically increased by their transport substrates, we characterized the effects of cholesterol on the ATPase activity of purified ABCA1 using liposomes of various lipid compositions. ABCA1 showed substantial ATPase activity (20–30 nmol |$\cdot$| min−1 |$\cdot$| mg−1) only in liposomes containing anionic lipids, including phosphatidylserine. Cholesterol increased the ATPase activity by 1.6- to 3-fold in the presence of anionic lipids. Moreover, phosphatidylserine addition to BHK/ABCA1 cells increased phosphatidylcholine and cholesterol efflux to apoA-I. Next, we investigated the sterol specificity of ABCA1. The ATPase activity of ABCA1 was strongly enhanced by desmosterol and zymosterol, similar to cholesterol. In contrast, 7-dehydrocholesterol and lathosterol weakly increased the ATPase activity, and no increase was observed with stigmasterol or brassicasterol. These findings suggest that ABCA1 transports cholesterol and prefers cholesterol over plant sterols as a transport substrate. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Decommissioning state of Plutonium Fuel Fabrication Facility; Dismantling the glove box W-9 and equipment interior, and a part of tunnel F1

Author

Nagai, Yuya, Shuji, Yoshiyuki, Kawasaki, Takeshi, Aita, Takahiro, Kimura, Yasuhisa, Nemoto, Yasunori, Onuma, Takesi, Tomiyama, Noboru, Hirano, koji, Usui, Yasuhiro, Nidaira, Seiichiro, Saito, Takahiro, Matsumoto, Jin, and Hirano, Hiroshi

Abstract

日本原子力研究開発機構は多くの原子力施設を保有しているが、その多くで老朽化・高経年化への対応、東日本大震災及び福島第一原子力発電所の事故を受けた耐震化や新規制基準への対応が求められ、多額の予算を要する状況である。このため、役割を終えた原子力施設についても根本的なリスク低減及び維持管理費用の削減のために施設の廃止措置を進めることが望ましいが、廃止措置及び発生する放射性廃棄物の処理処分に必要な施設の整備・維持管理にも多額の費用が必要となる。この状況を踏まえ、原子力機構では(1)継続利用する施設を絞り込む「施設の集約化・重点化」、(2)新規制基準・耐震化対応、高経年化対策、リスク低減対策等の「施設の安全確保」及び(3)廃止措置、廃棄物の処理処分といった「バックエンド対策」を3つの柱とした「施設中長期計画」を策定した。本計画において、プルトニウム燃料第二開発室は廃止施設として位置付けられており、施設内に設置された設備の解体撤去を進めている。今回の解体撤去対象は、焙焼還元炉、ペレット粉砕設備、これらを包蔵するグローブボックスNo.W-9及びW-9と隣々接の工程室内に設置されているグローブボックスNo.D-1とを連結するトンネル形状のグローブボックスNo.F-1の一部であり、許認可等による約4年の作業中断期間を含めて平成26年2月から令和2年2月の約6年間をかけて作業を実施した。本報告書では、本解体撤去における作業実績、解体撤去を通して得られた知見をまとめたものである, Japan Atomic Energy Agency (JAEA) manages wide range of nuclear facilities. Many of these facilities are required to be performed adjustment with the aging and complement with the new regulatory standards and the earthquake resistant, since the Great East Japan Earthquake and the Fukushima Daiichi Nuclear Power Station accident. It is therefore desirable to promote decommissioning of facilities that have reached the end of their productive life in order to reduce risk and maintenance costs. However, the progress of facility decommissioning require large amount of money and radioactive waste storage space. In order to address these issues, JAEA has formulated a "The Medium/Long-Term Management Plan of JAEA Facilities" with three pillars: (1) consolidation and prioritization of facilities, (2) assurance of facility safety, and (3) back-end countermeasures. In this plan, Plutonium Fuel Fabrication Facility has been selected as primary decommissioned facility, and dismantling of equipment in the facilities have been underway. In this report, size reduction activities of the glove box W-9 and a part of tunnel F-1, which was connected to W-9, are presented, and the obtained findings are highlighted. The glovebox W-9 had oxidation & reduction furnace, and pellet crushing machine as equipment interior. The duration of activity took six years from February 2014 to February 2020, including suspended period of 4 years due to the enhanced authorization approval process

Published
2023

28. ABCB1/MDR1/P‐gp employs an ATP‐dependent twist‐and‐squeeze mechanism to export hydrophobic drugs.

Author

Kodan, Atsushi, Futamata, Ryota, Kimura, Yasuhisa, Kioka, Noriyuki, Nakatsu, Toru, Kato, Hiroaki, and Ueda, Kazumitsu

Subjects
HYDROPHOBIC compounds, EXTRACELLULAR space, CHROMATIN-remodeling complexes, ATP-binding cassette transporters, P-glycoprotein, CRYSTAL structure
Abstract

ABCB1, also called MDR1 or P‐glycoprotein, exports various hydrophobic compounds and plays an essential role as a protective physiological barrier in several organs, including the brain, testis, and placenta. However, little is known about the structural mechanisms that allow ABCB1 to recognize hydrophobic compounds of diverse structures or the coupling of ATP hydrolysis to uphill substrate export. High‐resolution X‐ray crystal structures of the pre‐ and post‐transport states and FRET analyses in living cells have revealed that an aromatic hydrophobic network at the top of the inner cavity is key for the conformational change in ABCB1 that is triggered by a hydrophobic substrate. ATP binding, but not hydrolysis, induces a progressive network that results in a twisting motion of the whole protein, squeezing out the substrate directly to the extracellular space. This twist‐and‐squeeze mechanism by which ABCB1 exports hydrophobic substrates is distinct from those of other transporters. [ABSTRACT FROM AUTHOR]

Published
2021
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32. Decommissioning activities and R&D of nuclear facilities in the second midterm plan

Author

Terunuma, Akihiro, Mimura, Ryuji, Nagashima, Hisao, Aoyagi, Yoshitaka, Hirokawa, Katsunori, Uta, Masato, Ishimori, Yuu, Kuwabara, Jun, Okamoto, Hisato, Kimura, Yasuhisa, Koizumi, Kenji, Suzuki, Hajime, Hirose, Hideyuki, Usui, Hideo, Kubota, Shintaro, Takahashi, Nobuo, and Morimoto, Yasuyuki

Abstract

原子力機構は、平成22年4月から平成27年3月までの期間における中期目標を達成するための計画(以下「第2期中期計画」という。)を作成した。また、上記期間中の各年度の業務運営に関する計画(以下「年度計画」という。)を定めている。バックエンド研究開発部門は、この第2期中期計画及び年度計画に基づいて、廃止措置技術開発と原子力施設の廃止措置を進めてきた。本報告は、バックエンド研究開発部門が第2期中期に実施した廃止措置技術開発と原子力施設の廃止措置の結果についてまとめたものである。, Japan Atomic Energy Agency formulated the plan to achieve the medium-term target in the period of April 2010 to March 2015(hereinafter referred to as "the second medium-term plan"). JAEA determined the plan for the business operations of each year (hereinafter referred to as "the year plan"). This report is that the Sector of Decommissioning and Radioactive Waste Management has summarized the results of the decommissioning technology development and decommissioning of nuclear facilities which were carried out in the second medium-term plan.

Published
2016

35. Vinexin family (SORBS) proteins play different roles in stiffness-sensing and contractile force generation

Author

Ichikawa, Takafumi, primary, Kita, Masahiro, additional, Matsui, Tsubasa S., additional, Nagasato, Ayaka Ichikawa, additional, Araki, Tomohiko, additional, Chiang, Shian-Huey, additional, Sezaki, Takuhito, additional, Kimura, Yasuhisa, additional, Ueda, Kazumitsu, additional, Deguchi, Shinji, additional, Saltiel, Alan R., additional, and Kioka, Noriyuki, additional

Published
2017
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