Mutations in valosin-containing protein (VCP) decrease ADP/ATP translocation across the mitochondrial membrane and impair energy metabolism in human neurons

Mutations in the gene encoding valosin-containing protein (VCP) lead to multisystem proteinopathies including frontotemporal dementia. We have previously shown that patient-derived VCP mutant fibroblasts exhibit lower mitochondrial membrane potential, uncoupled respiration, and reduced ATP levels. This study addresses the underlying basis for mitochondrial uncoupling using VCP knockdown neuroblastoma cell lines, induced pluripotent stem cells (iPSCs), and iPSC-derived cortical neurons from patients with pathogenic mutations in VCP. Using fluorescent live cell imaging and respiration analysis we demonstrate a VCP mutation/knockdown-induced dysregulation in the adenine nucleotide translocase, which results in a slower rate of ADP or ATP translocation across the mitochondrial membranes. This deregulation can explain the mitochondrial uncoupling and lower ATP levels in VCP mutation-bearing neurons via reduced ADP availability for ATP synthesis. This study provides evidence for a role of adenine nucleotide translocase in the mechanism underlying altered mitochondrial function in VCP-related degeneration, and this new insight may inform efforts to better understand and manage neurodegenerative disease and other proteinopathies

Convection in colloidal suspensions with particle-concentration-dependent viscosity

The onset of thermal convection in a horizontal layer of a colloidal suspension is investigated in terms of a continuum model for binary-fluid mixtures where the viscosity depends on the local concentration of colloidal particles. With an increasing difference between the viscosity at the warmer and the colder boundary the threshold of convection is reduced in the range of positive values of the separation ratio psi with the onset of stationary convection as well as in the range of negative values of psi with an oscillatory Hopf bifurcation. Additionally the convection rolls are shifted downwards with respect to the center of the horizontal layer for stationary convection (psi>0) and upwards for the Hopf bifurcation (psi<0).Comment: 8 pages, 6 figures, submitted to European Physical Journal

Modulation of Localized States in Electroconvection

We report on the effects of temporal modulation of the driving force on a particular class of localized states, known as worms, that have been observed in electroconvection in nematic liquid crystals. The worms consist of the superposition of traveling waves and have been observed to have unique, small widths, but to vary in length. The transition from the pure conduction state to worms occurs via a backward bifurcation. A possible explanation of the formation of the worms has been given in terms of coupled amplitude equations. Because the worms consist of the superposition of traveling waves, temporal modulation of the control parameter is a useful probe of the dynamics of the system. We observe that temporal modulation increases the average length of the worms and stabilizes worms below the transition point in the absence of modulation.Comment: 4 pages, 4 figure

The Charge Form Factor of the Neutron from the Reaction \pol{2H}(\pol{e},e'n)p

We report on the first measurement of spin-correlation parameters in quasifree electron scattering from vector-polarized deuterium. Polarized electrons were injected into an electron storage ring at a beam energy of 720~MeV. A Siberian snake was employed to preserve longitudinal polarization at the interaction point. Vector-polarized deuterium was produced by an atomic beam source and injected into an open-ended cylindrical cell, internal to the electron storage ring. The spin correlation parameter A^V_{ed} was measured for the reaction \pol{2H}(\pol{e},e'n)p at a four-momentum transfer squared of 0.21 (GeV/c)^2 from which a value for the charge form factor of the neutron was extracted.Comment: 4 pages, 5 file

Observation of a Coherence Length Effect in Exclusive Rho^0 Electroproduction

Exclusive incoherent electroproduction of the rho^0(770) meson from 1H, 2H, 3He, and 14N targets has been studied by the HERMES experiment at squared four-momentum transfer Q**2>0.4 GeV**2 and positron energy loss nu from 9 to 20 GeV. The ratio of the 14N to 1H cross sections per nucleon, known as the nuclear transparency, was found to decrease with increasing coherence length of quark-antiquark fluctuations of the virtual photon. The data provide clear evidence of the interaction of the quark- antiquark fluctuations with the nuclear medium.Comment: RevTeX, 5 pages, 3 figure

Determination of the Deep Inelastic Contribution to the Generalised Gerasimov-Drell-Hearn Integral for the Proton and Neutron

The virtual photon absorption cross section differences [sigma_1/2-sigma_3/2] for the proton and neutron have been determined from measurements of polarised cross section asymmetries in deep inelastic scattering of 27.5 GeV longitudinally polarised positrons from polarised 1H and 3He internal gas targets. The data were collected in the region above the nucleon resonances in the kinematic range nu < 23.5 GeV and 0.8 GeV**2 < Q**2 < 12 GeV**2. For the proton the contribution to the generalised Gerasimov-Drell-Hearn integral was found to be substantial and must be included for an accurate determination of the full integral. Furthermore the data are consistent with a QCD next-to-leading order fit based on previous deep inelastic scattering data. Therefore higher twist effects do not appear significant.Comment: 6 pages, 3 figures, 1 table, revte