415 research outputs found
Magnetic Collective Mode Dispersion in High Temperature Superconductors
Recent neutron scattering experiments in the superconducting state of YBCO
have been interpreted in terms of a magnetic collective mode whose dispersion
relative to the commensurate wavevector has a curvature opposite in sign to a
conventional magnon dispersion. The purpose of this article is to demonstrate
that simple linear response calculations are in support of a collective mode
interpretation, and to explain why the dispersion has the curvature it does.Comment: 3 pages, revtex, 4 encapsulated postscript figure
Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interaction
Polyglutamine expansion in the N terminus of huntingtin (htt) causes selective neuronal dysfunction and cell death by unknown mechanisms. Truncated htt expressed in vitro produced htt immunoreactive cytoplasmic bodies (htt bodies). The fibrillar core of the mutant htt body resisted protease treatment and contained cathepsin D, ubiquitin, and heat shock protein (HSP) 40. The shell of the htt body was composed of globules 14-34 nm in diameter and was protease sensitive. HSP70, proteasome, dynamin, and the htt binding partners htt interacting protein 1 (HIP1), SH3-containing Grb2-like protein (SH3GL3), and 14.7K-interacting protein were reduced in their normal location and redistributed to the shell. Removal of a series of prolines adjacent to the polyglutamine region in htt blocked formation of the shell of the htt body and redistribution of dynamin, HIP1, SH3GL3, and proteasome to it. Internalization of transferrin was impaired in cells that formed htt bodies. In cortical neurons of Huntington's disease patients with early stage pathology, dynamin immunoreactivity accumulated in cytoplasmic bodies. Results suggest that accumulation of a nonfibrillar form of mutant htt in the cytoplasm contributes to neuronal dysfunction by sequestering proteins involved in vesicle trafficking
Physiologically regulated transgenic ABCA1 does not reduce amyloid burden or amyloid‐beta peptide levels in vivo
J Lipid Res. 2007 Apr;48(4):914-23. Epub 2007 Jan 18.
Physiologically regulated transgenic ABCA1 does not reduce amyloid burden or amyloid-beta peptide levels in vivo.
Hirsch-Reinshagen V, Chan JY, Wilkinson A, Tanaka T, Fan J, Ou G, Maia LF, Singaraja RR, Hayden MR, Wellington CL.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
Abstract
ABCA1-deficient mice have low levels of poorly lipidated apolipoprotein E (apoE) and exhibit increased amyloid load. To test whether excess ABCA1 protects from amyloid deposition, we crossed APP/PS1 mice to ABCA1 bacterial artificial chromosome (BAC) transgenic mice. Compared with wild-type animals, the ABCA1 BAC led to a 50% increase in cortical ABCA1 protein and a 15% increase in apoE abundance, demonstrating that this BAC supports modest ABCA1 overexpression in brain. However, this was observed only in animals that do not deposit amyloid. Comparison of ABCA1/APP/PS1 mice with APP/PS1 controls revealed no differences in levels of brain ABCA1 protein, amyloid, Abeta, or apoE, despite clear retention of ABCA1 overexpression in the livers of these animals. To further investigate ABCA1 expression in the amyloid-containing brain, we then compared ABCA1 mRNA and protein levels in young and aged cortex and cerebellum of APP/PS1 and ABCA1/APP/PS1 animals. Compared with APP/PS1 controls, aged ABCA1/APP/PS1 mice exhibited increased ABCA1 mRNA, but not protein, selectively in cortex. Additionally, ABCA1 mRNA levels were not increased before amyloid deposition but were induced only in the presence of extensive Abeta and amyloid levels. These data suggest that an induction of ABCA1 expression may be associated with late-stage Alzheimer's neuropathology.
PMID: 17235115 [PubMed - indexed for MEDLINE
Interactome network analysis identifies multiple caspase-6 interactors involved in the pathogenesis of HD
Caspase-6 (CASP6) has emerged as an important player in Huntington disease (HD), Alzheimer disease (AD) and cerebral ischemia, where it is activated early in the disease process. CASP6 also plays a key role in axonal degeneration, further underscoring the importance of this protease in neurodegenerative pathways. As a protein's function is modulated by its protein-protein interactions we performed a high throughput yeast-2-hybrid (Y2H) screen against ∼17,000 human proteins to gain further insight into the function of CASP6. We identified a high confidence list of 87 potential CASP6 interactors. From this list, 61% are predicted to contain a CASP6 recognition site. Of nine candidate substrates assessed, six are cleaved by CASP6. Proteins that did not contain a predicted CASP6 recognition site were assessed using a LUMIER assay approach and 51% were further validated as interactors by this method. Of note, 54% of the high-confidence interactors identified show alterations in human HD brain at the mRNA level, and there is a significant enrichment for previously validated huntingtin (HTT) interactors. One protein of interest, STK3, a proapoptotic kinase, was validated biochemically to be a CASP6 substrate. Furthermore, our results demonstrate that in striatal cells expressing mutant huntingtin (mHTT) an increase in full length and fragment levels of STK3 are observed. We further show that caspase-3 is not essential for the endogenous cleavage of STK3. Characterization of the interaction network provides important new information regarding key pathways of interactors of CASP6 and highlights potential novel therapeutic targets for HD, AD and cerebral ischemia
The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease.
J Biol Chem. 2005 Dec 30;280(52):43243-56. Epub 2005 Oct 5.
The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease.
Hirsch-Reinshagen V, Maia LF, Burgess BL, Blain JF, Naus KE, McIsaac SA, Parkinson PF, Chan JY, Tansley GH, Hayden MR, Poirier J, Van Nostrand W, Wellington CL.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V4Z 5H5, Canada.
Abstract
ABCA1, a cholesterol transporter expressed in the brain, has been shown recently to be required to maintain normal apoE levels and lipidation in the central nervous system. In addition, ABCA1 has been reported to modulate beta-amyloid (Abeta) production in vitro. These observations raise the possibility that ABCA1 may play a role in the pathogenesis of Alzheimer disease. Here we report that the deficiency of ABCA1 does not affect soluble or guanidine-extractable Abeta levels in Tg-SwDI/B or amyloid precursor protein/presenilin 1 (APP/PS1) mice, but rather is associated with a dramatic reduction in soluble apoE levels in brain. Although this reduction in apoE was expected to reduce the amyloid burden in vivo, we observed that the parenchymal and vascular amyloid load was increased in Tg-SwDI/B animals and was not diminished in APP/PS1 mice. Furthermore, we observed an increase in the proportion of apoE retained in the insoluble fraction, particularly in the APP/PS1 model. These data suggested that ABCA1-mediated effects on apoE levels and lipidation influenced amyloidogenesis in vivo.
PMID: 16207707 [PubMed - indexed for MEDLINE
Upper critical field for underdoped high-T_c superconductors. Pseudogap and stripe--phase
We investigate the upper critical field in a stripe--phase and in the
presence of a phenomenological pseudogap. Our results indicate that the
formation of stripes affects the Landau orbits and results in an enhancement of
. On the other hand, phenomenologically introduced pseudogap leads to a
reduction of the upper critical field. This effect is of particular importance
when the magnitude of the gap is of the order of the superconducting transition
temperature. We have found that a suppression of the upper critical field takes
place also for the gap that originates from the charge--density waves.Comment: 7 pages, 5 figure
Charge and spin inhomogeneous phases in the Ferromagnetic Kondo Lattice Model
We study numerically the one-dimensional ferromagnetic Kondo lattice. This
model is widely used to describe nickel and manganese perovskites. Due to the
competition between double and super-exchange, we find a region where the
formation of magnetic polarons induces a charge-ordered state. This ordering is
present even in the absence of any inter-site Coulomb repulsion. There is an
insulating gap associated to the charge structure formation. We also study the
insulator-metal transition induced by a magnetic field which removes
simultaneously both charge and spin ordering.Comment: 7 pages, 11 figure
Antiferromagnetic Domains and Superconductivity in UPt3
We explore the response of an unconventional superconductor to spatially
inhomogeneous antiferromagnetism (SIAFM). Symmetry allows the superconducting
order parameter in the E-representation models for UPt3 to couple directly to
the AFM order parameter. The Ginzburg-Landau equations for coupled
superconductivity and SIAFM are solved numerically for two possible SIAFM
configurations: (I) abutting antiferromagnetic domains of uniform size, and
(II) quenched random disorder of `nanodomains' in a uniform AFM background. We
discuss the contributions to the free energy, specific heat, and order
parameter for these models. Neither model provides a satisfactory account of
experiment, but results from the two models differ significantly. Our results
demonstrate that the response of an E_{2u} superconductor to SIAFM is strongly
dependent on the spatial dependence of AFM order; no conclusion can be drawn
regarding the compatibility of E_{2u} superconductivity with UPt3 that is
independent of assumptions on the spatial dependence of AFMComment: 12 pages, 13 figures, to appear in Phys. Rev.
Ab initio Quantum and ab initio Molecular Dynamics of the Dissociative Adsorption of Hydrogen on Pd(100)
The dissociative adsorption of hydrogen on Pd(100) has been studied by ab
initio quantum dynamics and ab initio molecular dynamics calculations. Treating
all hydrogen degrees of freedom as dynamical coordinates implies a high
dimensionality and requires statistical averages over thousands of
trajectories. An efficient and accurate treatment of such extensive statistics
is achieved in two steps: In a first step we evaluate the ab initio potential
energy surface (PES) and determine an analytical representation. Then, in an
independent second step dynamical calculations are performed on the analytical
representation of the PES. Thus the dissociation dynamics is investigated
without any crucial assumption except for the Born-Oppenheimer approximation
which is anyhow employed when density-functional theory calculations are
performed. The ab initio molecular dynamics is compared to detailed quantum
dynamical calculations on exactly the same ab initio PES. The occurence of
quantum oscillations in the sticking probability as a function of kinetic
energy is addressed. They turn out to be very sensitive to the symmetry of the
initial conditions. At low kinetic energies sticking is dominated by the
steering effect which is illustrated using classical trajectories. The steering
effects depends on the kinetic energy, but not on the mass of the molecules.
Zero-point effects lead to strong differences between quantum and classical
calculations of the sticking probability. The dependence of the sticking
probability on the angle of incidence is analysed; it is found to be in good
agreement with experimental data. The results show that the determination of
the potential energy surface combined with high-dimensional dynamical
calculations, in which all relevant degrees of freedon are taken into account,
leads to a detailed understanding of the dissociation dynamics of hydrogen at a
transition metal surface.Comment: 15 pages, 9 figures, subm. to Phys. Rev.
Spin Susceptibility in Underdoped
We report a comprehensive polarized and unpolarized neutron scattering study
of the evolution of the dynamical spin susceptibility with temperature and
doping in three underdoped single crystals of the \YBCO{6+x} high temperature
superconductor: \YBCO{6.5} (Tc = 52 K), \YBCO{6.7} (Tc = 67 K), and \YBCO{6.85}
(T_c = 87 K). Theoretical implications of these data are discussed, and a
critique of recent attempts to relate the spin excitations to the
thermodynamics of high temperature superconductors is given.Comment: minor revisions, to appear in PR
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