Establishing the Japan-Store house of animal radiobiology experiments (J-SHARE), a large-scale necropsy and histopathology archive providing international access to important radiobiology data.

Projects evaluating the effects of radiation, within the National Institutes of Quantum and Radiological Science and Technology (QST), National Institute of Radiological Sciences (NIRS), have focused on risk analyses for life shortening and cancer prevalence using laboratory animals. Genetic and epigenetic alterations in radiation-induced tumors have been also analyzed with the aim of better understanding mechanisms of radiation carcinogenesis. As well as the economic and practical limitations of repeating such large-scale experiments, ethical considerations make it vital that we store and share the pathological data and samples of the animal experiments for future use.

Expression of focal adhesion kinase in mouse cumulus-oocyte complexes, and effect of phosphorylation at Tyr397 on cumulus expansion.

We investigated the expression of focal adhesion kinase (FAK) in mouse cumulus-oocyte complexes (COCs), as well as the role of FAK phosphorylation at Tyr397 during oocyte maturation. The effect of inhibiting FAK phosphorylation at Tyr397 during in vitro maturation (IVM) on subsequent fertilization and preimplantation embryo development was also examined. Western blotting analyses revealed that total and Tyr397-phosphorylated FAK were expressed in vivo in both cumulus cells and oocytes.

Distribution and Y397 phosphorylation of focal adhesion kinase on follicular development in the mouse ovary.

Several protein tyrosine kinases (PTKs) are identified as follicle survival factors that suppress apoptosis in granulosa cells. Focal adhesion kinase (FAK/PTK2) interacts with numerous signaling partners and is important for cell adhesion, survival and other vital processes in which FAK autophosphorylation at Y397 (pY397 FAK) is critical for activating signaling pathways. Despite its important roles in apoptosis, the expression and function of FAK in the ovaries remain unknown.

Adrenomedullin: a possible regulator of germinal vesicle breakdown.

Adrenomedullin (ADM) is a multifunctional hormone that regulates processes as diverse as blood pressure and cell growth. Although expressed in the ovary, the role of ADM in this organ is not clear. In the present study, we found the expression of ADM receptor and receptor activity-modifying proteins in mouse cumulus cells but not in the oocytes.

New water-soluble prodrugs of HIV protease inhibitors based on O-->N intramolecular acyl migration.

To improve the low water-solubility of HIV protease inhibitors, we synthesized water-soluble prodrugs of KNI-272 and KNI-279 which are potent HIV-1 protease inhibitors consisting of an Apns-Thz core structure (Apns; allophenylnorstatine, Thz; thiazolidine-4-carboxylic acid) as an inhibitory machinery. The prodrugs, which contained an O-acyl peptidomimetic structure with an ionized amino group leading to the increase of water-solubility, were designed to regenerate the corresponding parent drugs based on the O-->N intramolecular acyl migration reaction at the alpha-hydroxy-beta-amino acid residue, that is allophenylnorstatine. The synthetic prodrugs 3, 4, 6, and 7 improved the water-solubility (>300mg/mL) more than 4000-fold in comparison with the parent compounds, which is the practically acceptable value as water-soluble drugs.