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Kunimaru, Takanori; Mikake, Shinichiro; Nishio, Kazuhisa; Tsuruta, Tadahiko; Matsuoka, Toshiyuki; Ishibashi, Masayuki; Ueno, Takashi; Tokuyasu, Shingo; Daimaru, Shuji; Takeuchi, Ryuji; et al.
JAEA-Review 2012-020, 178 Pages, 2012/06
JAEA-Review-2012-020.pdf:33.16MB
Japan Atomic Energy Agency (JAEA) at Tono Geoscience Center (TGC) is pursuing a geoscientific research and development project namely the Mizunami Underground Research Laboratory (MIU) Project in crystalline rock environment in order to construct scientific and technological basis for geological disposal of High-level Radioactive Waste (HLW). The MIU Project has three overlapping phases: Surface-based Investigation phase (Phase I), Construction phase (Phase II), and Operation phase (Phase III). The MIU Project has been ongoing the Phase II. And Phase III started in 2010 fiscal year. This report shows the results of the investigation, construction and collaboration studies in fiscal year 2010, as a part of the Phase II based on the MIU Master Plan updated in 2002.
Yamazaki, Yuji*; Tamada, Taro; Kasai, Noriyuki*; Urakawa, Itaru*; Aono, Yukiko*; Hasegewa, Hisashi*; Fujita, Toshiro*; Kuroki, Ryota; Yamashita, Takeyoshi*; Fukumoto, Seiji*; et al.
Journal of Bone and Mineral Research, 23(9), p.1509 - 1518, 2008/09
Times Cited Count：151 Percentile：94.39Fibroblast growth factor (FGF)23 is proposed to play a physiological role in the regulation of phosphate and vitamin D metabolism; deranged circulatory levels of FGF23 cause several diseases with abnormal mineral metabolism. We developed two antibodies (FN1 and FC1) that recognize the N- and C-terminal regions of FGF23, respectively. Both FN1 and FC1 inhibited FGF23 activity in a cell-based Klotho-dependent reporter assay. The present study using neutralizing antibodies confirms that FGF23 is a physiological regulator of phosphate and vitamin D metabolism. Then, we addressed the mechanism of action for these neutralizing antibodies. Structural analysis of the FGF23/FN1-Fab complex revealed that FN1 masked putative FGF receptor-binding sites in the N-terminal domain of FGF23, while biochemical analyses showed that FC1 interfered with the association between FGF23 and Klotho by binding to the C-terminal domain of FGF23. Taken together, our results suggest that the N- and C-terminal domains of FGF23 are responsible for association with cognate FGF receptors and Klotho, respectively, and that these interactions are indispensable for FGF23 activity.
