Recessive mutations in parkin are the most common cause of familial early-onset Parkinson's disease (PD). Recent studies suggest that certain parkin mutants may exert dominant toxic effects to cultured cells and such dominant toxicity can lead to progressive dopaminergic (DA) neuron degeneration in Drosophila. To explore whether mutant parkin could exert similar pathogenic effects to mammalian DA neurons in vivo, we developed a BAC (bacterial artificial chromosome) transgenic mouse model expressing a C-terminal truncated human mutant parkin (Parkin-Q311X) in DA neurons driven by a dopamine transporter promoter. Parkin-Q311X mice exhibit multiple late-onset and progressive hypokinetic motor deficits. Stereological analyses reveal that the mutant mice develop age-dependent DA neuron degeneration in substantia nigra accompanied by a significant loss of DA neuron terminals in the striatum. Neurochemical analyses reveal a significant reduction of the striatal dopamine level in mutant mice, which is significantly correlated with their hypokinetic motor deficits. Finally, mutant Parkin-Q311X mice, but not wild-type controls, exhibit age-dependent accumulation of proteinase K-resistant endogenous ␣-synuclein in substantia nigra and colocalized with 3-nitrotyrosine, a marker for oxidative protein damage. Hence, our study provides the first mammalian genetic evidence that dominant toxicity of a parkin mutant is sufficient to elicit agedependent hypokinetic motor deficits and DA neuron loss in vivo, and uncovers a causal relationship between dominant parkin toxicity and progressive ␣-synuclein accumulation in DA neurons. Our study underscores the need to further explore the putative link between parkin dominant toxicity and PD.
The relationship between construction output and economic growth has been well discussed by construction economists. Most of the previous studies found a positive correlation between gross domestic product (GDP) per capita and various measures of construction output. However, cross-sectional analysis was commonly adopted but longitudinal analysis has been called upon. Furthermore, recent research argued that non-linear relationship between GDP and construction output exists because of different stages of economic development in different countries. They explained the phenomenon by means of the change of the growth rates of construction output at different stages of economic development, but the argument has not yet been rigorously tested. With the availability of long time-series of data of Hong Kong construction industry, this paper attempts to test longitudinally the relationship between the real growth rate of construction output and the real growth rate of GDP. It was found that the growth rate of GDP led that of construction output, and as the growth rate of GDP increased, the growth rate of construction output was marginally diminishing. It agrees with the proposition that construction industry is relatively inefficient in productivity improvement and the accumulation of capital investment results in a marginally diminishing growth of construction output.Hong Kong construction industry, construction growth, GDP growth, economic development,
To achieve the efficient utilization of low-concentration mine gas, reduce resource waste and alleviate environmental pollution, the high-temperature oxidation of low-concentration gas at a concentration range of 1.00% to 1.50%, which is directly discharged into the atmosphere during coal mine production, was carried out to recover heat for reuse. The gas oxidation equipment was improved for the heating process and the safety of low-concentration gas oxidation under a high-temperature environment was evaluated. The experimental results showed that the reactor could provide a 1000 °C high-temperature oxidation environment for gas oxidation after installing high-temperature resistant ceramics. The pressure variation curves of the reactor with air and different concentrations of gas were similar. Due to the thermal expansion, the air pressure slightly increased and then returned to normal pressure. In contrast, the low-concentration gas exhibited a stable pressure response in the high-temperature environment of 1000 °C. The outlet pressure was significantly greater than the inlet pressure, and the pressure difference between the inlet and outlet exhibited a trend to increase with the gas concentration. The minimum pressure difference was 4 kPa (air) and the maximum was 11 kPa (1.50% gas). The explosion limit varied with the temperature and the blend of oxidation products. The ratio of measured gas pressure to air pressure after oxidation was below the explosion criterion, indicating that the measured concentration of gas is still safe after the shift of the explosion limit, which provides a safe concentration range for the efficient use of low-concentration gas in the future.
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