Exposure of rats to the pesticide and complex I inhibitor rotenone reproduces features of Parkinson's disease, including selective nigrostriatal dopaminergic degeneration and alpha-synuclein-positive cytoplasmic inclusions (Betarbet et al., 2000; Sherer et al., 2003). Here, we examined mechanisms of rotenone toxicity using three model systems. In SK-N-MC human neuroblastoma cells, rotenone (10 nm to 1 microm) caused dose-dependent ATP depletion, oxidative damage, and death. To determine the molecular site of action of rotenone, cells were transfected with the rotenone-insensitive single-subunit NADH dehydrogenase of Saccharomyces cerevisiae (NDI1), which incorporates into the mammalian ETC and acts as a "replacement" for endogenous complex I. In response to rotenone, NDI1-transfected cells did not show mitochondrial impairment, oxidative damage, or death, demonstrating that these effects of rotenone were caused by specific interactions at complex I. Although rotenone caused modest ATP depletion, equivalent ATP loss induced by 2-deoxyglucose was without toxicity, arguing that bioenergetic defects were not responsible for cell death. In contrast, reducing oxidative damage with antioxidants, or by NDI1 transfection, blocked cell death. To determine the relevance of rotenone-induced oxidative damage to dopaminergic neuronal death, we used a chronic midbrain slice culture model. In this system, rotenone caused oxidative damage and dopaminergic neuronal loss, effects blocked by alpha-tocopherol. Finally, brains from rotenone-treated animals demonstrated oxidative damage, most notably in midbrain and olfactory bulb, dopaminergic regions affected by Parkinson's disease. These results, using three models of increasing complexity, demonstrate the involvement of oxidative damage in rotenone toxicity and support the evaluation of antioxidant therapies for Parkinson's disease.
This review looks at the efforts that are being made to modify the surface of poly(dimethylsiloxane) (PDMS) microchannels, in order to enhance applicability in the field of microfluidics. Many surface modifications of PDMS have been performed for electrophoretic separations, but new modifications are being done for emerging applications such as heterogeneous immunoassays and cell-based bioassays. These new modification techniques are powerful because they impart biospecificity to the microchannel surfaces and reduce protein adsorption. Most of these applications require the use of aqueous or polar solvents, which makes surface modification a very important topic.
This work demonstrates a large-scale batch fabrication of GaN light-emitting diodes (LEDs) with patterned multi-layer graphene (MLG) as transparent conducting electrodes. MLG films were synthesized using a chemical vapor deposition (CVD) technique on nickel films and showed typical CVD-synthesized MLG film properties, possessing a sheet resistance of [Formula: see text] with a transparency of more than 85% in the 400-800 nm wavelength range. The MLG was applied as the transparent conducting electrodes of GaN-based blue LEDs, and the light output performance was compared to that of conventional GaN LEDs with indium tin oxide electrodes. Our results present a potential development toward future practical application of graphene electrodes in optoelectronic devices.
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