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Disruption of neuronal iron homeostasis and oxidative stress are closely related to the pathogenesis of Parkinson's disease (PD). Ginkgetin, a natural biflavonoid isolated from leaves ofGinkgo bilobaL, has many known effects, including anti-inflammatory, anti-influenza virus, and anti-fungal activities, but its underlying mechanism of the neuroprotective effects in PD remains unclear. The present study utilized PD models induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to explore the neuroprotective ability of ginkgetinin vivoandin vitro. Our results showed that ginkgetin could provide significant protection from MPP+-induced cell damagein vitroby decreasing the levels of intracellular reactive oxygen species and maintaining mitochondrial membrane potential. Meanwhile, ginkgetin dramatically inhibited cell apoptosis induced by MPP+ through the caspase-3 and Bcl2/Bax pathway. Moreover, ginkgetin significantly improved sensorimotor coordination in a mouse PD model induced by MPTP by dramatically inhibiting the decrease of tyrosine hydroxylase expression in the substantia nigra and superoxide dismutase activity in the striatum. Interestingly, ginkgetin could strongly chelate ferrous ion and thereby inhibit the increase of the intracellular labile iron pool through downregulating L-ferritin and upregulating transferrin receptor 1. These results indicate that the neuroprotective mechanism of ginkgetin against neurological injury induced by MPTP occurs via regulating iron homeostasis. Therefore, ginkgetin may provide neuroprotective therapy for PD and iron metabolism disorder related diseases. [ABSTRACT FROM AUTHOR]

The velocity space scattering of an anisotropic electron beam (T⊥b /T∥b >11) flowing along a background magnetic field B 0 through a cold plasma is investigated using both linear theory and 2D particle-in-cell simulations. Here, ⊥ and ∥ represent the directions perpendicular and parallel to B 0, respectively. In this scenario, we find that two primary instabilities contribute to the scattering in electron pitch angle: an electrostatic electron beam instability and a predominantly parallel-propagating electromagnetic whistler anisotropy instability. Our results show that at relative beam densities nb /ne ≤ 0.05 and beam temperature anisotropies Tb⊥ /Tb∥ ≤ 25, the electrostatic beam instability grows much faster than the whistler instabilities for a reasonably fast hot beam. The enhanced fluctuating fields from the beam instability scatter the beam electrons, slowing their average speed and increasing their parallel temperature, thereby increasing their pitch angles. In an inhomogeneous magnetic field, such as the geomagnetic field, this could result in beam electrons scattered out of the loss cone. After saturation of the electrostatic instability, the parallel-propagating whistler anisotropy instability shows appreciable growth, provided that the beam density and late-time anisotropy are sufficiently large. Although the whistler anisotropy instability acts to pitch-angle scatter the electrons, reducing perpendicular energy in favor of parallel energy, these changes are weak compared to the pitch-angle increases resulting from the deceleration of the beam due to the electrostatic instability. [ABSTRACT FROM AUTHOR]

Turbulent particle transport is investigated with a quasilinear theory that is motivated by the boron impurity transport experiments in the Alcator C-Mod. Eigenvalue problems for sets of reduced fluid equations for multi-component plasmas are solved for the self-consistent fluctuating field vectors composed of the electric potential φ, the main ion density δni, the impurity density δnz and the ion temperature fluctuation δTi. For Alcator C-Mod parameters, we investigate two drift wave models: (1) the density-gradient-driven impurity drift wave and (2) the ion-temperature-gradient-driven ion temperature gradient (ITG) mode. Analytic and numerical results for particle transport coefficients are derived and compared with the transport data and the neoclassical theory. We explore the ability of the model to explain impurity density profiles in three confinement regimes: H-mode, I-mode and internal transport barrier (ITB) regime in C-Mod. Related experiments reported on the Large Helical Device are briefly discussed. [ABSTRACT FROM AUTHOR]

While Ras is well-known to function on the plasma membrane (PM) to mediate growth factor signaling, increasing evidence suggests that Ras has complex roles in the cytoplasm. To uncover these roles, we screened a cDNA library and isolated H-Ras-binding proteins that also influence Ras functions. Many isolated proteins regulate trafficking involving endosomes; CHMP6/VPS20 and VPS4A, which interact with ESCRT-III (Endosomal Sorting Complex Required for Transport-III), were chosen for further study. We showed that the binding is direct and occurs in endosomes. Furthermore, the binding is most efficient when H-Ras has a functional effector-binding loop, and is GTP-bound and ubiquitylated. CHMP6 and VPS4A also bound to N-Ras but not K-Ras. Repressing CHMP6 and VPS4A blocked Ras-induced transformation, which correlated with inefficient Ras localization to the PM as measured by cell fractionation and photobleaching. Moreover, silencing CHMP6 and VPS4A also blocked epidermal growth factor receptor (EGFR) recycling. These data suggest that Ras interacts with key ESCRT-III components to promote recycling of itself and EGFR back to the PM to create a positive feedback loop to enhance growth factor signaling. [ABSTRACT FROM AUTHOR]

The electron temperature gradient (ETG) mode, which is a universal mechanism for turbulent electron thermal transport in plasmas, is produced and verified in steady-state, collisionless hydrogen plasma of the Columbia Linear Machine. Electron temperature profiles with strong gradients are produced by DC acceleration in a remote biased mesh and subsequent thermalization. Finite amplitude ∼5%, steady-state oscillations at ∼0.3-0.5MHz (in the plasma frame), with azimuthal wave numbers m∼14-16 and parallel wave number k∥∼0.01cm-1 are measured. The massively parallel gyrokinetic toroidal code is used to study these modes. The results show that in the linear phase, the dispersion relation is consistent with kinetic theory. In the nonlinear stage, very strong nonlinear wave coupling gives rise to an inverse cascade of the energy from the fastest growing high-m modes to low-m nonlinear oscillations, which are consistent with the measured azimuthal mode spectrum. The radial structure of the fluctuation also agrees with the experiment. An inward radial shift of the peak of the potential fluctuation occurs during the nonlinear saturation and fluctuation fingers extend radially out to the edge plasma. Three-wave coupling mechanism is involved in the saturation of ETG modes. The simulations show a power law spectrum of the turbulence which suggests that the renormalization theory is appropriate to interpret the turbulent thermal flux. [ABSTRACT FROM AUTHOR]

Two-dimensional particle-in-cell simulations are performed to study electron acceleration in collisionless magnetic reconnection. The process of electron acceleration is investigated by tracing typical electron trajectories. When there is no initial guide field, the electrons can be accelerated in both the X-type and O-type regions. In the X-type region, the electrons can be reflected back and enter the acceleration region several times before they leave the diffusion region. In this way, the electrons can be accelerated by the inductive electric field to high energy. In the O-type region, the trapped electrons can be accelerated when they are trapped in the magnetic island. When there is an initial guide field, the electrons can only be accelerated in the X-type region, and no obvious acceleration is observed in the O-type region. In the X-type region, the electrons are not demagnetized and they gyrate with the force of the guide field. Although no electron reflection is observed in this region, the acceleration efficiency can be enhanced through staying longer time in the diffusion region due to their gyration motion. [ABSTRACT FROM AUTHOR]