γ-synuclein is a novel player in the control of body lipid metabolism

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Modulation of α-synuclein expression in transgenic animals for modelling synucleinopathies — is the juice worth the squeeze?

Studies of various animal models have made a substantial contribution to the recent progress in understanding the molecular and cellular basis of neurodegenerative disorders. Modelling of neuro-degeneration by genetic alteration of laboratory animals became one of the most powerful tools of modern experimental neurology. The crucial event in pathogenesis of neurodegenerative diseases known as synucleinopathies is modification of α-synuclein metabolism caused by missense mutations, increased expression of the gene, or impaired degradation or intracellular compart-mentalisation of the protein. Therefore, manipulations with expression of α-synuclein in laboratory animals were widely used for creating models of these diseases. In the present review we discuss strong and weak sides of such models, what has been already learned from studies of these animals and what types of models might be useful to further our knowledge about pathogenesis of different synucleinopathies

Implementation of higher-order absorbing boundary conditions for the Einstein equations

We present an implementation of absorbing boundary conditions for the Einstein equations based on the recent work of Buchman and Sarbach. In this paper, we assume that spacetime may be linearized about Minkowski space close to the outer boundary, which is taken to be a coordinate sphere. We reformulate the boundary conditions as conditions on the gauge-invariant Regge-Wheeler-Zerilli scalars. Higher-order radial derivatives are eliminated by rewriting the boundary conditions as a system of ODEs for a set of auxiliary variables intrinsic to the boundary. From these we construct boundary data for a set of well-posed constraint-preserving boundary conditions for the Einstein equations in a first-order generalized harmonic formulation. This construction has direct applications to outer boundary conditions in simulations of isolated systems (e.g., binary black holes) as well as to the problem of Cauchy-perturbative matching. As a test problem for our numerical implementation, we consider linearized multipolar gravitational waves in TT gauge, with angular momentum numbers l=2 (Teukolsky waves), 3 and 4. We demonstrate that the perfectly absorbing boundary condition B_L of order L=l yields no spurious reflections to linear order in perturbation theory. This is in contrast to the lower-order absorbing boundary conditions B_L with L<l, which include the widely used freezing-Psi_0 boundary condition that imposes the vanishing of the Newman-Penrose scalar Psi_0.Comment: 25 pages, 9 figures. Minor clarifications. Final version to appear in Class. Quantum Grav

Improved outer boundary conditions for Einstein's field equations

In a recent article, we constructed a hierarchy B_L of outer boundary conditions for Einstein's field equations with the property that, for a spherical outer boundary, it is perfectly absorbing for linearized gravitational radiation up to a given angular momentum number L. In this article, we generalize B_2 so that it can be applied to fairly general foliations of spacetime by space-like hypersurfaces and general outer boundary shapes and further, we improve B_2 in two steps: (i) we give a local boundary condition C_2 which is perfectly absorbing including first order contributions in 2M/R of curvature corrections for quadrupolar waves (where M is the mass of the spacetime and R is a typical radius of the outer boundary) and which significantly reduces spurious reflections due to backscatter, and (ii) we give a non-local boundary condition D_2 which is exact when first order corrections in 2M/R for both curvature and backscatter are considered, for quadrupolar radiation.Comment: accepted Class. Quant. Grav. numerical relativity special issue; 17 pages and 1 figur

Explicit solution of the linearized Einstein equations in TT gauge for all multipoles

We write out the explicit form of the metric for a linearized gravitational wave in the transverse-traceless gauge for any multipole, thus generalizing the well-known quadrupole solution of Teukolsky. The solution is derived using the generalized Regge-Wheeler-Zerilli formalism developed by Sarbach and Tiglio.Comment: 9 pages. Minor corrections, updated references. Final version to appear in Class. Quantum Gra

Modulation of p-eIF2α cellular levels and stress granule assembly/disassembly by trehalose

Stress granules (SGs) are an important component of cellular stress response. Compromised assembly of SGs as well as their premature or delayed disassembly affect physiology and survival of cells under stress or during recovery from stress. Consequently, abnormal turnover of SGs has been implicated in the development of various pathologies, including neurodegeneration. We found that pretreatment of cells with a natural disaccharide trehalose, a known autophagy enhancer, delays SG assembly and facilitates their premature post-stress disassembly. Mechanistically, the effect of trehalose on SGs is mediated via the p-eIF2α rather than autophagosome pathway. Trehalose increases pre-stress levels of p-eIF2α and its phosphatase subunits and promotes post-stress translational recovery. Upon prolonged treatment, trehalose impairs basal translation affecting production of transiently expressed proteins. Early translational recovery and SG disassembly induced by trehalose pretreatment can sensitise cells to stress and impair survival. Our study has important implications for the use of trehalose in studies of autophagic clearance of misfolded proteins and for targeting SGs as a possible therapeutic approach in neurodegenerative and other diseases

Charge neutralization in vacuum for non-conducting and isolated objects using directed low-energy electron and ion beams

We propose using ions and electrons of energy 1 eV–10 eV for neutralizing the charges on the non-conducting or isolated surfaces of high-sensitivity experiments. The mirror surfaces of the test masses of the laser interferometer gravitational observatory are used as an example of the implementation of this method. By alternatively directing beams of positive and negative charges towards the mirror surfaces, we ensure the neutralization of the total charge as well as the equalization of the surface charge distribution to within a few eV of the potential of the ground reference of the vacuum system. This method is compatible with operation in high vacuum, does not require measuring the potential of the mirrors and is expected not to damage sensitive optical surfaces

Regularity of the Einstein Equations at Future Null Infinity

When Einstein's equations for an asymptotically flat, vacuum spacetime are reexpressed in terms of an appropriate conformal metric that is regular at (future) null infinity, they develop apparently singular terms in the associated conformal factor and thus appear to be ill-behaved at this (exterior) boundary. In this article however we show, through an enforcement of the Hamiltonian and momentum constraints to the needed order in a Taylor expansion, that these apparently singular terms are not only regular at the boundary but can in fact be explicitly evaluated there in terms of conformally regular geometric data. Though we employ a rather rigidly constrained and gauge fixed formulation of the field equations, we discuss the extent to which we expect our results to have a more 'universal' significance and, in particular, to be applicable, after minor modifications, to alternative formulations.Comment: 43 pages, no figures, AMS-TeX. Minor revisions, updated to agree with published versio