Role of mitochondria in Parkinson disease

The cause of the selective degeneration of nigrostriatal neurons in Parkinson disease (PD) has remained largely unknown. Exceptions include rare missense mutations in the alpha-synuclein gene on chromosome 4, a potentially pathogenic mutation affecting the ubiquitin pathway, and mutations in the parkin gene on chromosome 6. However, unlike classical PD, the latter syndrome is not associated with the formation of typical Lewy bodies. In contrast, a biochemical defect of complex I of the mitochondrial respiratory chain has been described in a relatively large group of confirmed PD cases. Recent cybrid studies indicate that the complex I defect in PD has a genetic cause and that it may arise from mutations in the mitochondrial DNA, Sequence analysis of the mitochondrial genome supports the view that mitochondrial point mutations are involved in PD pathogenesis. However, although mitochondria function as regulators in several known forms of cell death, their exact involvement in PD has remained unresolved. This is of relevance because classical apoptosis does not appear to play a major role in the degeneration of the parkinsonian nigra

The time course of conceptualizing and formulating processes during the production of simple sentences

The psychological process of producing sentences includes conceptualization (selecting to-beexpressed conceptual content) and formulation (translating conceptual content into syntactic structures of a language). There is ample evidence, both intuitive and experimental, that the conceptualizing and formulating processes often proceed concurrently, not strictly serially. James Lindsley (Cognitive Psych.,1975, 7, 1-19; J.Psycholinguistic Res., 1976, 5, 331-354) has developed a concurrent model which proved succesful in an experimental situation where simple English Subject-Verb (SV) sentences such as “The boy is greeting”,”The girl is kicking” were produced as descriptions of pictures which showed actor and action. The measurements were reaction times defined as the interval between the moment a picture appeared on a screen and the onset of the vocal utterance by the speaker. Lindsley could show, among other things, that the formulation process for an SV sentence doesn’t start immediately after the actor of a picture (that is, the conceptual content underlying the surface Subject phrase) has been identified, but is somewhat delayed. The delay was needed, according to Lindsley, in order to prevent dysfluencies (hesitations) between surface Subject and verb. We replicated Lindsley’s data for Dutch. However, his model proved inadequate when we added Dutch Verb-Subject (VS) constructions which are obligatory in certain syntactic contexts but synonymous with their SV counterparts. A sentence production theory which is being developed by the first author is able to provide an accurate account of the data. The abovementioned delay is attributed to certain precautions the sentence generator has to take in case of SV but not of VS sentences. These precautions are related to the goal of attaining syntactic coherence of the utterance as a whole, not to the prevention of dysfluencies

A Simple Boltzmann Transport Equation for Ballistic to Diffusive Transient Heat Transport

Developing simplified, but accurate, theoretical approaches to treat heat transport on all length and time scales is needed to further enable scientific insight and technology innovation. Using a simplified form of the Boltzmann transport equation (BTE), originally developed for electron transport, we demonstrate how ballistic phonon effects and finite-velocity propagation are easily and naturally captured. We show how this approach compares well to the phonon BTE, and readily handles a full phonon dispersion and energy-dependent mean-free-path. This study of transient heat transport shows i) how fundamental temperature jumps at the contacts depend simply on the ballistic thermal resistance, ii) that phonon transport at early times approach the ballistic limit in samples of any length, and iii) perceived reductions in heat conduction, when ballistic effects are present, originate from reductions in temperature gradient. Importantly, this framework can be recast exactly as the Cattaneo and hyperbolic heat equations, and we discuss how the key to capturing ballistic heat effects is to use the correct physical boundary conditions.Comment: 9 pages, 5 figure

Hamiltonian for coupled flux qubits

An effective Hamiltonian is derived for two coupled three-Josephson-junction (3JJ) qubits. This is not quite trivial, for the customary "free" 3JJ Hamiltonian is written in the limit of zero inductance L. Neglecting the self-flux is already dubious for one qubit when it comes to readout, and becomes untenable when discussing inductive coupling. First, inductance effects are analyzed for a single qubit. For small L, the self-flux is a "fast variable" which can be eliminated adiabatically. However, the commonly used junction phases are_not_ appropriate "slow variables", and instead one introduces degrees of freedom which are decoupled from the loop current to leading order. In the quantum case, the zero-point fluctuations (LC oscillations) in the loop current diverge as L->0. Fortunately, they merely renormalize the Josephson couplings of the effective (two-phase) theory. In the coupled case, the strong zero-point fluctuations render the full (six-phase) wave function significantly entangled in leading order. However, in going to the four-phase theory, this uncontrollable entanglement is integrated out completely, leaving a computationally usable mutual-inductance term of the expected form as the effective interaction.Comment: REVTeX4, 16pp., one figure. N.B.: "Alec" is my first, and "Maassen van den Brink" my family name. Informal note. v2: completely rewritten; correction of final result and major expansion. v3: added numerical verification plus a discussion of Ref. [2

Quantum Zeno effect in the Cooper-pair transport through a double-island Josephson system

Motivated by recent experiments, we analyze transport of Cooper pairs through a double-island Josephson qubit. At low bias in a certain range of gate voltages coherent superpositions of charge states play a crucial role. Analysis of the evolution of the density matrix allows us to cover a wide range of parameters, incl. situations with degenerate levels, when dissipation strongly affects the coherent eigenstates. At high noise levels the so-called Zeno effect can be observed, which slows down the transport. Our analysis explains certain features of the I-V curves, in particular the visibility and shape of resonant peaks and lines

Approach to the extremal limit of the Schwarzschild-de Sitter black hole

The quasinormal-mode spectrum of the Schwarzschild-de Sitter black hole is studied in the limit of near-equal black-hole and cosmological radii. It is found that the mode_frequencies_ agree with the P"oschl-Teller approximation to one more order than previously realized, even though the effective_potential_ does not. Whether the spectrum approaches the limiting one uniformly in the mode index is seen to depend on the chosen units (to the order investigated). A perturbation framework is set up, in which these issues can be studied to higher order in future.Comment: REVTeX4, 4pp., no figures. N.B. "Alec" is my first, and "Maassen van den Brink" my family name. v2: added numerical verificatio

Detection of phosphotyrosine, insulin receptor substrate-1 and growth factor receptor-bound protein-2 in the magnocellular forebrain system and hypothalamus of cat and man

Insulin action initiated by insulin binding to its cognate receptor is performed via phosphorylation of tyrosines on substrate proteins by the receptor tyrosine kinase domain. This process involves autophosphorylation of tyrosine residues in the cytoplasmic domain of the receptor. A comparable action is mediated by nerve growth factor (NGF) and epidermal growth factor (EGF) receptors. Few articles have been directed to the morphological regional distribution in the brain of phosphotyrosine, using antibodies. The first extensive description that proved a topographical distribution for phosphotyrosine in the rat brain was conducted by Marani and Maassen. It was shown that alternating areas positive and negative for phosphotyrosine could be described. These areas showed different localizations that were in good agreement with the biochemical results obtained by others. Moreover, fetal and postnatal series confirmed the results that phosphotyrosine content is extremely high in the developing brain as compared to the mature brain. In the mature brain, the phosphotyrosine localization is also found in the neuropil, not only in neurons. High concentrations of phosphotyrosine in a regional distribution are found in the rat rhinencephalon, the cortex, the basal ganglia (mainly in neostriatum and substantia nigra), hypothalamus and the habenular nuclei. In the hippocampus, the positivity for phosphotyrosine can be detected in the pyramidal cells and the neuropil. The hippocampal subdivisions of CA1 and CA3 can be weakly discerned. Topographical studies of the distribution of insulin receptor substrate-1 (IRS-1), growth factor receptor-bound protein-2 (GRB-2) or its adaptor molecule and substrate of insulin receptor kinase (She) that complexes to GRB-2 and conducts insulin action towards the Ras complex are absent for the brain.Biomedical Reviews 1996; 5: 73-82