RESUMO
The level of vitamin D-binding protein (DBP) is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD), suggesting a relationship with its pathogenesis. In this study, we investigated whether and how DBP is related to AD using several different approaches. A pull-down assay and a surface plasmon resonance binding assay indicated direct interactions between purified DBP and amyloid beta (Aß), which was confirmed in the brain of AD patients and transgenic AD model mice by immunoprecipitation assay and immunohistochemical double-staining method. Moreover, atomic force microscopic examination revealed that DBP reduced Aß aggregation in vitro. DBP also prevented Aß-mediated death in cultured mouse hippocampal HT22 cell line. Finally, DBP decreased Aß-induced synaptic loss in the hippocampus and rescued memory deficits in mice after injection of Aß into the lateral ventricle. These results provide converging evidence that DBP attenuates the harmful effects of Aß by a direct interaction, and suggest that DBP is a promising therapeutic agent for the treatment of AD.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Proteína de Ligação a Vitamina D/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/farmacologia , Animais , Apoptose , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Linhagem Celular , Hipocampo/metabolismo , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Ligação Proteica , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Sinaptofisina/metabolismo , Proteína de Ligação a Vitamina D/genética , Proteína de Ligação a Vitamina D/farmacologiaRESUMO
High-power single-spatial-mode near-IR laser diodes are mixed in periodically poled LiNbO(3) (PPLN) to generate broadly tunable mid IR-radiation. Conversion efficiencies to the mid IR up to 0.017%/W are demonstrated, and up to 31 microW of power is generated at the spectroscopically important 4.3-microm wavelength. We achieved broadband mid-IR tunability by mixing a wavelength-tunable laser-diode pump source with a fixed-wavelength master oscillator power amplifier laser-diode signal source in a PPLN sample that has a poling period that varies from 21.0 to 22.6 microm in the direction transverse to the beam propagation. We generated mid-IR radiation from 4.1 to 4.3 microm with these laser sources, using a fixed 22.0-microm period region of the sample.
RESUMO
A method is developed for the quantitative assessment of microlens deficiencies caused by inaccuracies in the multistep mesa fabrication or by incomplete mass-transport smoothing. Analytical expressions are obtained and tolerable imperfections are deduced for the practical effort-saving fabrication of highperformance micro-optical elements.
