Signaling, Polyubiquitination, Trafficking, and Inclusions: Sequestosome 1/p62's Role in Neurodegenerative Disease

Aggregated misfolded proteins are hallmarks of most neurodegenerative diseases. In a chronic disease state, including pathologic situations of oxidative stress, these proteins are sequestered into inclusions. Accumulation of aggregated proteins can be prevented by chaperones, or by targeting their degradation to the UPS. If the accumulation of these proteins exceeds their degradation, they may impair the function of the proteasome. Alternatively, the function of the proteasome may be preserved by directing aggregated proteins to the autophagy-lysosome pathway for degradation. Sequestosome 1/p62 has recently been shown to interact with polyubiquitinated proteins through its UBA domain and may direct proteins to either the UPS or autophagosome. P62 is present in neuronal inclusions of individuals with Alzheimer's disease and other neurodegenerative diseases. Herein, we review p62's role in signaling, aggregation, and inclusion formation, and specifically as a possible contributor to Alzheimer's disease. The use of p62 as a potential target for the development of therapeutics and as a disease biomarker is also discussed

Constant effective mass across the phase diagram of high-Tc_{c} cuprates

We investigate the hole dynamics in two prototypical high temperature superconducting systems: La$_{2-x}$Sr$_{x}$CuO$_{4}$ and YBa$_{2}$Cu$_{3}$O$_{y}$ using a combination of DC transport and infrared spectroscopy. By exploring the effective spectral weight obtained with optics in conjunction with DC Hall results we find that the transition to the Mott insulating state in these systems is of the "vanishing carrier number" type since we observe no substantial enhancement of the mass as one proceeds to undoped phases. Further, the effective mass remains constant across the entire underdoped regime of the phase diagram. We discuss the implications of these results for the understanding of both transport phenomena and pairing mechanism in high-T$_{c}$ systems.Comment: 5 pages, 2 figure

Evaluation of Born and local effective charges in unoriented materials from vibrational spectra

We present an application of the Lorentz model in which fits to vibrational spectra or a Kramers Kronig analysis are employed along with several useful formalisms to quantify microscopic charge in unoriented (powdered) materials. The conditions under which these techniques can be employed are discussed, and we analyze the vibrational response of a layered transition metal dichalcogenide and its nanoscale analog to illustrate the utility of this approach.Comment: 9 pages, 1 figur

Optical investigations on Y2−xBixRu2O7Y_{2-x} Bi_x Ru_2 O_7: Electronic structure evolutions related to the metal-insulator transition

Optical conductivity spectra of cubic pyrochlore $Y_{2-x} Bi_x Ru_2 O_7$ (0.0$\leq${\it x}$\leq$2.0) compounds are investigated. As a metal-insulator transition (MIT) occurs around {\it x}$=$0.8, large spectral changes are observed. With increase of {\it x}, the correlation-induced peak between the lower and the upper Hubbard bands seems to be suppressed, and a strong mid-infrared feature is observed. In addition, the $p-d$ charge transfer peak shifts to the lower energies. The spectral changes cannot be explained by electronic structural evolutions in the simple bandwidth-controlled MIT picture, but are consistent with those in the filling-controlled MIT picture. In addition, they are also similar to the spectral changes of Y$_{2-x}$Ca$_{x}$Ru$_{2}$O$_{7}$ compounds, which is a typical filling-controlled system. This work suggests that, near the MIT, the Ru bands could be doped with the easily polarizable Bi cations.Comment: 5 figure

Magneto-optical investigation of the field-induced spin-glass insulator to ferromagnetic metallic transition of the bilayer manganite (La0.4_{0.4}Pr0.6_{0.6})1.2_{1.2}Sr1.8_{1.8}Mn2_2O7_7

We measured the magneto-optical response of (La$_{0.4}$Pr$_{0.6}$)$_{1.2}$Sr$_{1.8}$Mn$_2$O$_7$ in order to investigate the microscopic aspects of the magnetic field driven spin-glass insulator to ferromagnetic metal transition. Application of a magnetic field recovers the ferromagnetic state with an overall redshift of the electronic structure, growth of the bound carrier localization associated with ferromagnetic domains, development of a pseudogap, and softening of the Mn-O stretching and bending modes that indicate a structural change. We discuss field- and temperature-induced trends within the framework of the Tomioka-Tokura global electronic phase diagram picture and suggest that controlled disorder near a phase boundary can be used to tune the magnetodielectric response. Remnants of the spin-glass insulator to ferromagnetic metallic transition can also drive 300 K color changes in (La$_{0.4}$Pr$_{0.6}$)$_{1.2}$Sr$_{1.8}$Mn$_2$O$_7$.Comment: 9 pages, 8 figure

The in-plane electrodynamics of the superconductivity in Bi2Sr2CaCu2O8+d: energy scales and spectral weight distribution

The in-plane infrared and visible (3 meV-3 eV) reflectivity of Bi2Sr2CaCu2O8+d (Bi-2212) thin films is measured between 300 K and 10 K for different doping levels with unprecedented accuracy. The optical conductivity is derived through an accurate fitting procedure. We study the transfer of spectral weight from finite energy into the superfluid as the system becomes superconducting. In the over-doped regime, the superfluid develops at the expense of states lying below 60 meV, a conventional energy of the order of a few times the superconducting gap. In the underdoped regime, spectral weight is removed from up to 2 eV, far beyond any conventional scale. The intraband spectral weight change between the normal and superconducting state, if analyzed in terms of a change of kinetic energy is ~1 meV. Compared to the condensation energy, this figure addresses the issue of a kinetic energy driven mechanism.Comment: 13 pages with 9 figures include

Topology of amorphous tetrahedral semiconductors on intermediate lengthscales

Using the recently-proposed ``activation-relaxation technique'' for optimizing complex structures, we develop a structural model appropriate to a-GaAs which is almost free of odd-membered rings, i.e., wrong bonds, and possesses an almost perfect coordination of four. The model is found to be superior to structures obtained from much more computer-intensive tight-binding or quantum molecular-dynamics simulations. For the elemental system a-Si, where wrong bonds do not exist, the cost in elastic energy for removing odd-membered rings is such that the traditional continuous-random network is appropriate. Our study thus provides, for the first time, direct information on the nature of intermediate-range topology in amorphous tetrahedral semiconductors.Comment: 4 pages, Latex and 2 postscript figure

Structural, electronic, and dynamical properties of amorphous gallium arsenide: a comparison between two topological models

We present a detailed study of the effect of local chemical ordering on the structural, electronic, and dynamical properties of amorphous gallium arsenide. Using the recently-proposed ``activation-relaxation technique'' and empirical potentials, we have constructed two 216-atom tetrahedral continuous random networks with different topological properties, which were further relaxed using tight-binding molecular dynamics. The first network corresponds to the traditional, amorphous, Polk-type, network, randomly decorated with Ga and As atoms. The second is an amorphous structure with a minimum of wrong (homopolar) bonds, and therefore a minimum of odd-membered atomic rings, and thus corresponds to the Connell-Temkin model. By comparing the structural, electronic, and dynamical properties of these two models, we show that the Connell-Temkin network is energetically favored over Polk, but that most properties are little affected by the differences in topology. We conclude that most indirect experimental evidence for the presence (or absence) of wrong bonds is much weaker than previously believed and that only direct structural measurements, i.e., of such quantities as partial radial distribution functions, can provide quantitative information on these defects in a-GaAs.Comment: 10 pages, 7 ps figures with eps

Event-based relaxation of continuous disordered systems

A computational approach is presented to obtain energy-minimized structures in glassy materials. This approach, the activation-relaxation technique (ART), achieves its efficiency by focusing on significant changes in the microscopic structure (events). The application of ART is illustrated with two examples: the structure of amorphous silicon, and the structure of Ni80P20, a metallic glass.Comment: 4 pages, revtex, epsf.sty, 3 figure