Blood-derived amyloid-ß protein induces Alzheimer's disease pathologies.

The amyloid-ß protein (Aß) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aß deposited in the brain originates from the brain tissue itself. However, Aß is generated in both brain and peripheral tissues. Whether circulating Aß contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aß originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aß plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aß accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aß can enter the brain, form the Aß-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aß metabolism in both the brain and the periphery.

+Antisense oligonucleotide targeting survivin inhibits growth by inducing apoptosis in human osteosarcoma cells MG-63.

UNLABELLED: Survivin may play an important role in the development of osteosarcoma. In this study, we chose osteosarcoma cell line MG-63, which highly expressed survivin, to observe the effects of antisense oligonucleotide targeting survivin on the apoptosis induction and proliferation inhibition. It was shown in our results that the apoptosis rate and the proliferation inhibition rate increased significantly in survivin-positive cells MG-63 by using MTT and flow cytometry methods. We found that the growth inhibition rate and apoptosis rate were changed in a dose-dependent way. When the concentration of antisurvivin oligonucleotide was 600 nM, the effects reached the peak. RT-PCR and western-blot methods were used to detect the mRNA and protein expression of survivin in MG-63. We observed that the mRNA and protein expression of survivin reduced after transfected with antisurvivin oligonucleotides at the concentration of 200 nM, 400 nM and 600 nM. At the same time, we found that the mRNA and protein expression of Fas were up-regulated with the concentration of antisurvivin oligonucleotides from 200 nM to 600 nM. It was negative associated with the expression change of survivin. These data suggested that survivin should play an important role in the development of osteosarcoma and the survivin blockaded by using antisurvivin oligonucleotide could inhibit the proliferation and induce apoptosis of osteosarcoma by decreasing the expression of survivin and activate the Fas-mediated apoptosis. Down-regulation of survivin by antisense oligonucleotide might be an effective strategy to the treatment of osteosarcoma and might improve the therapeutic effect. KEYWORDS: osteosarcoma, Survivin, apoptosis, Fas.

Composition and temperature dependence of the dielectric, piezoelectric and elastic properties of pure PZT ceramics.

Pure (undoped) piezoelectric lead zirconate titanate (PZT) ceramic samples at compositions across the ferroelectric region of the phase diagram were prepared from sol-gel-derived fine powders. Excess lead oxide was included in the PZT powders to obtain dense (95-96% of theoretical density) ceramics with large grain size (>7 mum) and to control the lead stoichiometry. The dielectric, piezoelectric, and elastic properties were measured from 4.2 to 300 K. At very low temperatures, the extrinsic domain wall and thermal defect motions freeze out. The low-temperature dielectric data can be used to determine coefficients in a phenomenological theory. The extrinsic contribution to the properties can then be separated from the single-domain properties derived from the theory.