Nitrated α-Synuclein Induces the Loss of Dopaminergic Neurons in the Substantia Nigra of Rats

BACKGROUND: The pathology of Parkinson's disease (PD) is characterized by the degeneration of the nigrostriatal dopaminergic pathway, as well as the formation of intraneuronal inclusions known as Lewy bodies and Lewy neurites in the substantia nigra. Accumulations of nitrated alpha-synuclein are demonstrated in the signature inclusions of Parkinson's disease. However, whether the nitration of alpha-synuclein is relevant to the pathogenesis of PD is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, effect of nitrated alpha-synuclein to dopaminergic (DA) neurons was determined by delivering nitrated recombinant TAT-alpha-synuclein intracellular. We provide evidence to show that the nitrated alpha-synuclein was toxic to cultured dopaminergic SHSY-5Y neurons and primary mesencephalic DA neurons to a much greater degree than unnitrated alpha-synuclein. Moreover, we show that administration of nitrated alpha-synuclein to the substantia nigra pars compacta of rats caused severe reductions in the number of DA neurons therein, and led to the down-regulation of D(2)R in the striatum in vivo. Furthermore, when administered to the substantia nigra of rats, nitrated alpha-synuclein caused PD-like motor dysfunctions, such as reduced locomotion and motor asymmetry, however unmodified alpha-synuclein had significantly less severe behavioral effects. CONCLUSIONS/SIGNIFICANCE: Our results provide evidence that alpha-synuclein, principally in its nitrated form, induce DA neuron death and may be a major factor in the etiology of PD

Fuzzy Compensation and Load Disturbance Adaptive Control Strategy for Electro-Hydraulic Servo Pump Control System

Aiming at the high-precision position control of electro-hydraulic servo pump control system, a compensation control algorithm based on fuzzy control theory is proposed based on the classical PID control algorithm for the control of factors such as oil compression and system leakage. Firstly, a mathematical model of the system was established, and online identification of load disturbance was carried out. Then, oil compression and system leakage compensation controllers were established, and the position error caused by the load disturbance was compensated based on fuzzy control rules. Finally, the position control effect was verified using an experimental platform. The results show that the load disturbance compensation control strategy can significantly reduce the influence of load disturbance of the system. The steady-state accuracy of the system reached ±0.01 mm, which significantly enhanced the anti-disturbance ability of the system

Fuzzy Compensation and Load Disturbance Adaptive Control Strategy for Electro-Hydraulic Servo Pump Control System

Aiming at the high-precision position control of electro-hydraulic servo pump control system, a compensation control algorithm based on fuzzy control theory is proposed based on the classical PID control algorithm for the control of factors such as oil compression and system leakage. Firstly, a mathematical model of the system was established, and online identification of load disturbance was carried out. Then, oil compression and system leakage compensation controllers were established, and the position error caused by the load disturbance was compensated based on fuzzy control rules. Finally, the position control effect was verified using an experimental platform. The results show that the load disturbance compensation control strategy can significantly reduce the influence of load disturbance of the system. The steady-state accuracy of the system reached ±0.01 mm, which significantly enhanced the anti-disturbance ability of the system

Contrasting influences of human activities on hydrological drought regimes over China based on high-resolution simulations

How human activities have altered hydrological droughts (streamflow deficits) in China during the past five decades (1961–2016) is investigated using the latest version (v2.0) of PCR-GLOBWB model at high spatial resolution (~10 km). Although both human activities and climate variability have significant effects on river flows over China, there are large regional north-south contrasts. Over northern China, human activities generally intensify hydrological droughts. We find that human activities exacerbated drought deficit by about 70–200% from 2004 to 2015. In contrast, droughts over southern China are generally alleviated by human activities. For instance, irrigation and water management (such as reservoir operation and water abstraction) increase drought StDef (standardized drought deficit volume) by about 80% in the Yellow River (north) but reduce it by about 20% in the Yangtze River (south). Human activities slightly reduce drought deficit in the Yangtze River due to the combination of large reservoir storage and low ratio of agriculture consumption to abstracted irrigation water. In contrast, hydrological drought is aggravated in the semiarid Yellow River basin because of high water consumption from agricultural sectors. This study suggests that human activities have contrasting influences on hydrological drought characteristics in the northern (intensification) and southern (mitigation) parts of China. Therefore, it is critical to consider the variable roles of human activities on hydrological drought in China when developing mitigation and adaptation strategies

Construction and Immunogenicity Evaluation of Recombinant Adenovirus-Expressing Capsid Protein of Foot-and-Mouth Disease Virus Types O and A

The objective of this study was to construct a recombinant adenovirus expressing the foot-and-mouth disease virus (FMDV) capsid protein of types O and A for future FMDV vaccines to be used in the livestock industry for the reduction in losses caused by FMD outbreaks. Three recombinant adenoviruses, rAdv-P12A3B3C-OZK93, rAdv-P12A3B3C-OA58, and rAdv-P12A3C-AF72, were packaged, characterized, and amplified using the AdMaxTM adenovirus packaging system, and the humoral and cellular immunity levels were further evaluated in guinea pigs with monovalent or bivalent forms. The results showed that the three recombinant adenoviruses could elicit high levels of humoral and cellular immune responses against FMDV types O and A when immunizing monovalent or bivalent forms, and the immune effect changes with the change in the proportion of recombinant adenovirus types O and A, laying an important foundation for the future development of a new FMD live-carrier vaccine. These results implied that the recombinant adenovirus expressing the FMDV capsid protein of types O and A could be used to prevent FMDV in livestock

Deforestation-induced warming over tropical mountain regions regulated by elevation

International audienceAgriculture is expanding in tropical mountainous areas, yet its climatic effect is poorly understood. Here, we investigate how elevation regulates the biophysical climate impacts of deforestation over tropical mountainous areas by integrating satellite-observed forest cover changes into a high-resolution land-atmosphere coupled model. We show that recent forest conversion between 2000 and 2014 increased the regional warming by 0.022 ± 0.002 °C in the Southeast Asian Massif, 0.010 ± 0.007 °C in the Barisan Mountains (Maritime Southeast Asia), 0.042 ± 0.010 °C in the Serra da Espinhaço (South America) and 0.047 ± 0.008 °C in the Albertine Rift mountains (Africa) during the local dry season. The deforestation-driven local temperature anomaly can reach up to 2 °C where forest conversion is extensive. The warming from mountain deforestation depends on elevation, through the intertwined and opposing effects of increased albedo causing cooling and decreased evapotranspiration causing warming. As the elevation increases, the albedo effect increases in importance and the warming effect decreases, analogous to previously highlighted decreases of deforestation-induced warming with increasing latitude. As most new croplands are encroaching lands at low to moderate elevations, deforestation produces higher warming from suppressed evapotranspiration. Impacts of this additional warming on crop yields, land degradation and biodiversity of nearby intact ecosystems should be incorporated into future assessments