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To demonstrate that aluminum III (Al) interacts with PHFτ in neurofibrillary degeneration (NFD) of Alzheimer's disease (AD. brain, we developed a “chelating autoclave method” that allows Al chelation by using trivalent-cationic chelator desferrioxamine. Its application to AD brain sections before Morin histochemistry for Al attenuated the positive fluorescence of neurofibrillary tangles, indicating Al removal from them. This method, applied for immunostaining with phosphorylation-dependent anti-τ antibodies, significantly enhanced the PHFτ immunoreactivity of the NFD. These results suggest that each of the phosphorylated epitopes in PHFτ are partially masked by Al binding. Incubation of AD sections with AlCl3before Morin staining revealed Al accumulation with association to neurofibrillary tangles. Such incubation before immunostaining with the phosphorylation-dependent anti-τ antibodies abolished the immunolabeling of the NFD and this abolition was reversed by the Al chelation. These findings indicate cumulative Al binding to and thereby antigenic masking of the phosphorylated epitopes of PHFτ. Al binding was further documented for electrophoretically-resolved PHFτ on immunoblots, indicating direct Al binding to PHFτ. In vitroaggregation by AlCl3was observed for PHFτ but was lost on dephosphorylation of PHFτ. Taken together, phosphorylation-dependent and direct PHFτ-Al interaction occurs in the NFD of the AD brain.

To establish humanized mice with a knock-in (gene replacement) technique, we constructed a targeting vector which consists of the human prion protein and the loxP sequences. The introduced human prion protein with the loxP system in the embryonic stem cells was transmitted through the mouse germ line. Transient expression of Cre recombinase in the fertilized eggs resulted in the prion protein humanized mice. The Cre-loxP-mediated gene replacement is a simple and efficient method which is generally applicable to make humanized animal models.

The synthesis of bicyclo[9.3.1]pentadecatriene skeleton was investigated by employing cyclization reactions using two key precursors bearing acetylene cobalt complex. Cyclization for the synthesis of strained twelve-membered ring was achieved viaNicholas type reaction in reasonable yield. Reductive decomplexation of the dicobalt hexacarbonyl moiety of the cyclization product was achieved with n-Bu3SnH in the presence of a catalytic amount of NBS in 1,4-cyclohexadiene solvent.

The polymorphism at codon 219 of the prion protein gene (PRNP) was found in the general Japanese population with 6% allele frequency. Herein, we examined 85 cases of sporadic Creutzfeldt‐Jakob disease (CJD) for the codon 219 polymorphism. The codon 219Glu/Lysheterozygous polymorphism was not found in these CJD cases. In addition, we examined 43 patients with dementia of non‐CJD origin, and 4 were found to have the codon 219 Glu/Lysheterozygous polymorphism with a similar allele frequency as in the general population. Thus, the codon 219Glu/Lysheterozygous polymorphism might be uniquely excluded from sporadic CJD.

Lower selectivity for nitrate and nitrite was obtained when Pd was used as a cocatalyst on TiO2for photocatalytic oxidation of aqueous ammonia in the presence of oxygen. This is thought to be due to the fact that an N-containing intermediate formed by photocatalytic oxidation of ammonia on TiO2decomposed sequentially on Pd by thermal catalysis, with high selectivity for dinitrogen.

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