Neuromelanins in brain aging and Parkinson's disease: synthesis, structure, neuroinflammatory, and neurodegenerative role.

Neuromelanins are compounds accumulating in neurons of human and animal brain during aging, with neurons of substantia nigra and locus coeruleus having the highest levels of neuromelanins. These compounds have melanic, lipid, peptide, and inorganic components and are contained inside special autolysosomes. Neuromelanins can participate in neuroprotective or toxic processes occurring in Parkinson's disease according to cellular environment.

Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson's disease.

During aging, neuronal organelles filled with neuromelanin (a dark-brown pigment) and lipid bodies accumulate in the brain, particularly in the substantia nigra, a region targeted in Parkinson's disease. We have investigated protein and lipid systems involved in the formation of these organelles and in the synthesis of the neuromelanin of human substantia nigra. Membrane and matrix proteins characteristic of lysosomes were found in neuromelanin-containing organelles at a lower number than in typical lysosomes, indicating a reduced enzymatic activity and likely impaired capacity for lysosomal and autophagosomal fusion.

Guiding of relativistic electron beams in dense matter by laser-driven magnetostatic fields.

Intense lasers interacting with dense targets accelerate relativistic electron beams, which transport part of the laser energy into the target depth. However, the overall laser-to-target energy coupling efficiency is impaired by the large divergence of the electron beam, intrinsic to the laser-plasma interaction. Here we demonstrate that an efficient guiding of MeV electrons with about 30 MA current in solid matter is obtained by imposing a laser-driven longitudinal magnetostatic field of 600 T.

Ion separation effects in mixed-species ablators for inertial-confinement-fusion implosions.

Recent efforts to demonstrate significant self-heating of the fuel and eventual ignition at the National Ignition Facility make use of plastic (CH) ablators [O. A. Hurricane et al.

Ion thermal decoupling and species separation in shock-driven implosions.

Anomalous reduction of the fusion yields by 50% and anomalous scaling of the burn-averaged ion temperatures with the ion-species fraction has been observed for the first time in D^{3}He-filled shock-driven inertial confinement fusion implosions. Two ion kinetic mechanisms are used to explain the anomalous observations: thermal decoupling of the D and ^{3}He populations and diffusive species separation. The observed insensitivity of ion temperature to a varying deuterium fraction is shown to be a signature of ion thermal decoupling in shock-heated plasmas.

Asymptotic separation in multispecies collisional plasma shocks.

When a piston drives a shock in a multicomponent plasma, residual separation of the ion species persists close to the piston-plasma boundary, long after the shock has propagated away from the boundary and has reached a (nearly) steady-state solution. This effect is observed in hybrid particle-in-cell simulations with two kinetic ion species and fluid electrons. It is a consequence of the different dynamics experienced by ions of different mass and charge-to-mass ratio and must be taken into account to properly model the physics of species separation in collisional plasma shocks.

Exploration of the transition from the hydrodynamiclike to the strongly kinetic regime in shock-driven implosions.

Clear evidence of the transition from hydrodynamiclike to strongly kinetic shock-driven implosions is, for the first time, revealed and quantitatively assessed. Implosions with a range of initial equimolar D3He gas densities show that as the density is decreased, hydrodynamic simulations strongly diverge from and increasingly overpredict the observed nuclear yields, from a factor of ∼2 at 3.1  mg/cm3 to a factor of 100 at 0.

First observations of nonhydrodynamic mix at the fuel-shell interface in shock-driven inertial confinement implosions.

A strong nonhydrodynamic mechanism generating atomic fuel-shell mix has been observed in strongly shocked inertial confinement fusion implosions of thin deuterated-plastic shells filled with 3He gas. These implosions were found to produce D3He-proton shock yields comparable to implosions of identical shells filled with a hydroequivalent 50∶50 D3He gas mixture. Standard hydrodynamic mixing cannot explain this observation, as hydrodynamic modeling including mix predicts a yield an order of magnitude lower than was observed.

Neuromelanins of human brain have soluble and insoluble components with dolichols attached to the melanic structure.

Neuromelanins (NMs) are neuronal pigments of melanic-lipidic type which accumulate during aging. They are involved in protective and degenerative mechanisms depending on the cellular context, however their structures are still poorly understood. NMs from nine human brain areas were analyzed in detail.

Plasma adiabatic lapse rate.

The plasma analog of an adiabatic lapse rate (or temperature variation with height) in atmospheric physics is obtained. A new source of plasma temperature gradient in a binary ion species mixture is found that is proportional to the concentration gradient ∇α and difference in average ionization states Z(2)-Z(1). Application to inertial-confinement-fusion implosions indicates a potentially strong effect in plastic (CH) ablators that is not modeled with mainline (single-fluid) simulations.

Rayleigh-Taylor instability of an ultrathin foil accelerated by the radiation pressure of an intense laser.

We report experimental evidence for a Rayleigh-Taylor-like instability driven by radiation pressure of an ultraintense (10(21) W/cm(2)) laser pulse. The instability is witnessed by the highly modulated profile of the accelerated proton beam produced when the laser irradiates a 5 nm diamondlike carbon (90% C, 10% H) target. Clear anticorrelation between bubblelike modulations of the proton beam and transmitted laser profile further demonstrate the role of the radiation pressure in modulating the foil.

Complete temporal characterization of asymmetric pulse compression in a laser wakefield.

We present complete experimental characterization of the temporal shape of an intense ultrashort 200-TW laser pulse driving a laser wakefield. The phase of the pulse was uniquely measured by using (second-order) frequency-resolved optical gating. The pulses are asymmetrically compressed and exhibit a positive chirp consistent with the expected asymmetric self-phase-modulation due to photon acceleration or deceleration in a relativistic plasma wave.

Near-GeV acceleration of electrons by a nonlinear plasma wave driven by a self-guided laser pulse.

The acceleration of electrons to approximately 0.8 GeV has been observed in a self-injecting laser wakefield accelerator driven at a plasma density of 5.5x10(18) cm(-3) by a 10 J, 55 fs, 800 nm laser pulse in the blowout regime.

Neuromelanins in various regions of human brain are associated with native and oxidized isoprenoid lipids.

Neuromelanin (NM) isolated from seven regions of the human brain is found to contain series of natural and oxidized isoprenoid lipids. Specifically, dolichols (dol) and dolichoic acids (dol-CA) with 14-22 and 14-21 isoprene units are identified. Standards of nor-dolichol and nor-dolichoic acid were used to determine the relative amounts of dol and dol-CA compared to the total lipids present in NM for each region.

Characterization of high-intensity laser propagation in the relativistic transparent regime through measurements of energetic proton beams.

Experiments were performed to investigate the propagation of a high intensity (I approximately 10(21) W cm(-2)) laser in foam targets with densities ranging from 0.9n(c) to 30n(c). Proton acceleration was used to diagnose the interaction.

Neuromelanins isolated from different regions of the human brain exhibit a common surface photoionization threshold.

Neuromelanin isolated from the premotor cortex, cerebellum, putamen, globus pallidus and corpus callosum of the human brain is studied by scanning probe and photoelectron emission microscopies and the results are compared with previously published work on neuromelanin from the substantia nigra. Scanning electron microscopy reveals common structure for all neuromelanins. All exhibit spherical entities of diameters between 200 and 400 nm, composed of smaller spherical substructures, approximately 30 nm in diameter.

New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals.

Neuronal pigments of melanic type were identified in the putamen, cortex, cerebellum, and other major regions of human brain. These pigments consist of granules 30 nm in size, contained in organelles together with lipid droplets, and they accumulate in aging, reaching concentrations as high as 1.5-2.

Neuromelanin can protect against iron-mediated oxidative damage in system modeling iron overload of brain aging and Parkinson's disease.

In Parkinson's disease (PD), dopamine neurons containing neuromelanin selectively degenerate. Neuromelanin binds iron and accumulates in aging. Iron accumulates in reactive form during aging, PD, and is involved in neurodegeneration.

Observation of synchrotron radiation from electrons accelerated in a petawatt-laser-generated plasma cavity.

The dynamics of plasma electrons in the focus of a petawatt laser beam are studied via measurements of their x-ray synchrotron radiation. With increasing laser intensity, a forward directed beam of x rays extending to 50 keV is observed. The measured x rays are well described in the synchrotron asymptotic limit of electrons oscillating in a plasma channel.

Dynamic control of laser-produced proton beams.

The emission characteristics of intense laser driven protons are controlled using ultrastrong (of the order of 10(9) V/m) electrostatic fields varying on a few ps time scale. The field structures are achieved by exploiting the high potential of the target (reaching multi-MV during the laser interaction). Suitably shaped targets result in a reduction in the proton beam divergence, and hence an increase in proton flux while preserving the high beam quality.

Active manipulation of the spatial energy distribution of laser-accelerated proton beams.

The spatial energy distributions of beams of protons accelerated by ultrahigh intensity (>10(19)Wcm2) picosecond laser pulse interactions with thin foil targets are investigated. Using separate, low intensity (<10(13)Wcm2) nanosecond laser pulses, focused onto the front surface of the target foil prior to the arrival of the high intensity pulse, it is demonstrated that the proton beam profile can be actively manipulated. In particular, results obtained with an annular intensity distribution at the focus of the low intensity beam are presented, showing smooth proton beams with a sharp circular boundary at all energies, which represents a significant improvement in the beam quality compared to irradiation with the picosecond beam alone.

Effect of laser intensity on fast-electron-beam divergence in solid-density plasmas.

Metal foil targets were irradiated with 1 mum wavelength (lambda) laser pulses of 5 ps duration and focused intensities (I) of up to 4x10;{19} W cm;{-2}, giving values of both Ilambda;{2} and pulse duration comparable to those required for fast ignition inertial fusion. The divergence of the electrons accelerated into the target was determined from spatially resolved measurements of x-ray K_{alpha} emission and from transverse probing of the plasma formed on the back of the foils. Comparison of the divergence with other published data shows that it increases with Ilambda;{2} and is independent of pulse duration.

Bright multi-keV harmonic generation from relativistically oscillating plasma surfaces.

The first evidence of x-ray harmonic radiation extending to 3.3 A, 3.8 keV (order n>3200) from petawatt class laser-solid interactions is presented, exhibiting relativistic limit efficiency scaling (eta approximately n{-2.

Neuromelanin and iron in human locus coeruleus and substantia nigra during aging: consequences for neuronal vulnerability.

In this study a comparative analysis of iron molecules during aging was performed in locus coeruleus (LC) and substantia nigra (SN), known targets of Parkinson's Disease (PD) and related disorders. LC and SN neurons, especially the SN pars compacta, degenerate in PD and other forms of parkinsonism. Iron and its major molecular forms, such as ferritin and neuromelanin (NM), were measured in LC and SN of normal subjects at various ages.