Altered muscarinic and nicotinic receptor densities in cortical and subcortical brain regions in Parkinson's disease

Muscarinic and nicotinic cholinergic receptors and choline acetyltransferase activity were studied in postmortem brain tissue from patients with histopathologically confirmed Parkinson's disease and matched control subjects. Using washed membrane homogenates from the frontal cortex, hippocampus, caudate nucleus, and putamen, saturation analysis of specific receptor binding was performed for the total number of muscarinic receptors with [3H]quinuclidinyl benzilate, for muscarinic M1 receptors with [3H]pirenzepine, for muscarinic M2 receptors with [3H]oxotremorine-M, and for nicotinic receptors with (-)-[3H]nicotine. In comparison with control tissues, choline acetyl-transferase activity was reduced in the frontal cortex and hippocampus and unchanged in the caudate nucleus and putamen of parkinsonian patients. In Parkinson's disease the maximal binding site density for [3H]quinuclidinyl benzilate was increased in the frontal cortex and unaltered in the hippocampus, caudate nucleus, and putamen. Specific [3H]pirenzepine binding was increased in the frontal cortex, unaltered in the hippocampus, and decreased in the caudate nucleus and putamen. In parkinsonian patients Bmax values for specific [3H]oxotremorine-M binding were reduced in the cortex and unchanged in the hippocampus and striatum compared with controls. Maximal (-)-[3H]nicotine binding was reduced in both the cortex and hippocampus and unaltered in both the caudate nucleus and putamen. Alterations of the equilibrium dissociation constant were not observed for any ligand in any of the brain areas examined. The present results suggest that both the innominatocortical and the septohippocampal cholinergic systems degenerate in Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS

Terguride stimulates locomotor activity at 2 months but not 10 months after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets

The mixed dopamine (DA) agonist/antagonist terguride acts as a DA antagonist on normosensitive receptors but shows DA agonistic properties at supersensitive DA receptors. Such a compound could offer an alternative to the treatment of Parkinson's disease with indirect or direct DA agonists. The present study compares the actions of terguride, 4-12 mg/kg i.p., in naive common marmosets with its effects in animals rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2 months or 10 months previously, in order to test its antiparkinsonian efficacy. Terguride reduced locomotor activity in naive common marmosets, similar to its effects in rodents and in line with the DA antagonistic activity of the compound. In marmosets treated with MPTP 2 months previously and exhibiting pronounced behavioural motor deficits, terguride stimulated locomotor activity, showing DA agonistic properties under these conditions. In contrast, the locomotor activity of animals that had recovered from MPTP treatment 10 months previously was not altered by terguride. It is concluded that terguride has anti-akinetic efficacy in this primate model of Parkinson's disease. In addition, terguride offers a unique opportunity to differentiate, pharmacologically, the extent of dopaminergic recovery from MPTP treatment in this primate species

Weak localization in mesoscopic hole transport: Berry phases and classical correlations

We consider phase-coherent transport through ballistic and diffusive two-dimensional hole systems based on the Kohn-Luttinger Hamiltonian. We show that intrinsic heavy-hole light-hole coupling gives rise to clear-cut signatures of an associated Berry phase in the weak localization which renders the magneto-conductance profile distinctly different from electron transport. Non-universal classical correlations determine the strength of these Berry phase effects and the effective symmetry class, leading even to antilocalization-type features for circular quantum dots and Aharonov-Bohm rings in the absence of additional spin-orbit interaction. Our semiclassical predictions are quantitatively confirmed by numerical transport calculations

Fluctuation-Driven Molecular Transport in an Asymmetric Membrane Channel

Channel proteins, that selectively conduct molecules across cell membranes, often exhibit an asymmetric structure. By means of a stochastic model, we argue that channel asymmetry in the presence of non-equilibrium fluctuations, fueled by the cell's metabolism as observed recently, can dramatically influence the transport through such channels by a ratchet-like mechanism. For an aquaglyceroporin that conducts water and glycerol we show that a previously determined asymmetric glycerol potential leads to enhanced inward transport of glycerol, but for unfavorably high glycerol concentrations also to enhanced outward transport that protects a cell against poisoning.Comment: REVTeX4, 4 pages, 3 figures; Accepted for publication in Phys. Rev. Let

Geometric quantum gate for trapped ions based on optical dipole forces induced by Gaussian laser beams

We present an implementation of quantum logic gates via internal state dependent displacements of ions in a linear Paul trap caused by optical dipole forces. Based on a general quantum analysis of the system dynamics we consider specific implementations with alkaline earth ions. For experimentally realistic parameters gate infidelities as low as $10^{-4}$ can be obtained.Comment: 10 pages, 4 figure

Characteristic energies, transition temperatures, and switching effects in clean SNS graphene nanostructures

We study proximity effects in clean nanoscale superconductor-normal metal-superconductor (S$\mid$N$\mid$S) graphene heterostructures using a self-consistent numerical solution to the continuum Dirac Bogoliubov-de Gennes (DBdG) equations. We obtain results for the pair amplitude and the local density of states (DOS), as a function of doping and of the geometrical parameters determining the width of the structures. The superconducting correlations are found to penetrate the normal graphene layers even when there is extreme mismatch in the normal and superconducting doping levels, where specular Andreev reflection dominates. The local DOS exhibits peculiar features, which we discuss, arising from the Dirac cone dispersion relation and from the interplay between the superconducting and Thouless energy scales. The corresponding characteristic energies emerge in the form of resonant peaks in the local DOS, that depend strongly on the doping level, as does the energy gap, which declines sharply as the relative difference in doping between the S and N regions is reduced. We also linearize the DBdG equations and develop an essentially analytical method that determines the critical temperature $T_c$ of an \sns nanostructure self-consistently. We find that for S regions that occupy a fraction of the coherence length, $T_c$ can undergo substantial variations as a function of the relative doping. At finite temperatures and by manipulating the doping levels, the self consistent pair amplitudes reveal dramatic transitions between a superconducting and resistive normal state of the structure. Such behavior suggests the possibility of using the proposed system as a carbon-based superconducting switch, turning superconductivity on or off by tuning the relative doping levels.Comment: 13 pages, figures include

Self-consistent simulation of quantum wires defined by local oxidation of Ga[Al]As heterostructures

We calculate the electronic width of quantum wires as a function of their lithographic width in analogy to experiments performed on nanostructures defined by local oxidation of Ga[Al]As heterostructures. Two--dimensional simulations of two parallel oxide lines on top of a Ga[Al]As heterostructure defining a quantum wire are carried out in the framework of Density Functional Theory in the Local Density Approximation and are found to be in agreement with measurements. Quantitative assessment of the influence of various experimental uncertainties is given. The most influential parameter turns out to be the oxide line depth, followed by its exact shape and the effect of background doping (in decreasing order).Comment: 5 pages, 6 figures; revised figures, clarified tex

Optically excited states in positronium

Optical excitation are reported of the 1 3S-2 3P transition in positronium, and a second excitation from n=2 to higher n states. The experiment used light from two pulsed dye lasers. Changes in the positronium annihilation rate during and after the laser pulse were used to deduce the excited state populations. The n=2 level was found to be saturable and excitable to a substantial fraction of n=2 positronium to higher levels. Preliminary spectroscopic measurements were performed on n=14 and n=15 positronium

Effect of spatial inhomogeneity on the mapping between strongly interacting fermions and weakly interacting spins

A combined analytical and numerical study is performed of the mapping between strongly interacting fermions and weakly interacting spins, in the framework of the Hubbard, t-J and Heisenberg models. While for spatially homogeneous models in the thermodynamic limit the mapping is thoroughly understood, we here focus on aspects that become relevant in spatially inhomogeneous situations, such as the effect of boundaries, impurities, superlattices and interfaces. We consider parameter regimes that are relevant for traditional applications of these models, such as electrons in cuprates and manganites, and for more recent applications to atoms in optical lattices. The rate of the mapping as a function of the interaction strength is determined from the Bethe-Ansatz for infinite systems and from numerical diagonalization for finite systems. We show analytically that if translational symmetry is broken through the presence of impurities, the mapping persists and is, in a certain sense, as local as possible, provided the spin-spin interaction between two sites of the Heisenberg model is calculated from the harmonic mean of the onsite Coulomb interaction on adjacent sites of the Hubbard model. Numerical calculations corroborate these findings also in interfaces and superlattices, where analytical calculations are more complicated.Comment: 7 pages, 6 figure

Mode Bifurcation and Fold Points of Complex Dispersion Curves for the Metamaterial Goubau Line

In this paper the complex dispersion curves of the four lowest-order transverse magnetic modes of a dielectric Goubau line ($\epsilon>0, \mu>0$) are compared with those of a dispersive metamaterial Goubau line. The vastly different dispersion curve structure for the metamaterial Goubau line is characterized by unusual features such as mode bifurcation, complex fold points, both proper and improper complex modes, and merging of complex and real modes