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

Reduced complement of dopaminergic neurons in the substantia nigra pars compacta of mice with a constitutive “low footprint” genetic knockout of alpha-synuclein

Previous studies of the alpha-synuclein null mutant mice on the C57Bl6 genetic background have revealed reduced number of dopaminergic neurons in their substantia nigra pars compacta (SNpc). However, the presence in genomes of the studied mouse lines of additional genetic modifications that affect expression of genes located in a close proximity to the alpha-synuclein-encoding Snca gene makes these data open to various interpretations. To unambiguously demonstrate that the absence of alpha-synuclein is the primary cause of the observed deficit of dopaminergic neurons, we employed a recently produced constituent alpha-synuclein knockout mouse line B6(Cg)-Sncatm1.2Vlb/J. The only modification introduced to the genome of these mice is a substitution of the first coding exon and adjusted short intronic fragments of the Snca gene by a single loxP site. We compared the number of dopaminergic neurons in the SNpc of this line, previously studied B6(Cg)-Sncatm1Rosl/J line and wild type littermate mice. A similar decrease was observed in both knockout lines when compared with wild type mice. In a recently published study we revealed no loss of dopaminergic neurons following conditional inactivation of the Snca gene in neurons of adult mice. Taken together, these results strongly suggest that alpha-synuclein is required for efficient survival or maturation of dopaminergic neurons in the developing SNpc but is dispensable for survival of mature SNpc dopaminergic neurons

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

Monomeric alpha-synuclein exerts a physiological role in brain ATP synthase

Misfolded α-synuclein is a key factor in the pathogenesis of Parkinson's disease (PD). However, knowledge about a physiological role for the native, unfolded α-synuclein is limited. Using brains of mice lacking α-, β-, and γ-synuclein, we report that extracellular monomeric α-synuclein enters neurons and localizes to mitochondria, interacts with ATP synthase subunit α, and modulates ATP synthase function. Using a combination of biochemical, live-cell imaging and mitochondrial respiration analysis, we found that brain mitochondria of α-, β-, and γ-synuclein knock-out mice are uncoupled, as characterized by increased mitochondrial respiration and reduced mitochondrial membrane potential. Furthermore, synuclein deficiency results in reduced ATP synthase efficiency and lower ATP levels. Exogenous application of low unfolded α-synuclein concentrations is able to increase the ATP synthase activity that rescues the mitochondrial phenotypes observed in synuclein deficiency. Overall, the data suggest that α-synuclein is a previously unrecognized physiological regulator of mitochondrial bioenergetics through its ability to interact with ATP synthase and increase its efficiency. This may be of particular importance in times of stress or PD mutations leading to energy depletion and neuronal cell toxicity

Deletion of alpha-synuclein decreases impulsivity in mice

The presynaptic protein alpha-synuclein, associated with Parkinson's Disease (PD), plays a role in dopaminergic neurotransmission and is implicated in impulse control disorders (ICDs) such as drug addiction. In this study we investigated a potential causal relationship between alpha-synuclein and impulsivity, by evaluating differences in motor impulsivity in the 5-choice serial reaction time task (5-CSRTT) in strains of mice that differ in the expression of the alpha-synuclein gene. C57BL/6JOlaHsd mice differ from their C57BL/6J ancestors in possessing a chromosomal deletion resulting in the loss of two genes, snca, encoding alpha-synuclein, and mmrn1, encoding multimerin-1. C57BL/6J mice displayed higher impulsivity (more premature responding) than C57BL/6JOlaHsd mice when the pre-stimulus waiting interval was increased in the 5-CSRTT. In order to ensure that the reduced impulsivity was indeed related to snca, and not adjacent gene deletion, wild type (WT) and mice with targeted deletion of alpha-synuclein (KO) were tested in the 5-CSRTT. Similarly, WT mice were more impulsive than mice with targeted deletion of alpha-synuclein. Interrogation of our ongoing analysis of impulsivity in BXD recombinant inbred mouse lines revealed an association of impulsive responding with levels of alpha-synuclein expression in hippocampus. Expression of beta- and gamma-synuclein, members of the synuclein family that may substitute for alpha-synuclein following its deletion, revealed no differential compensations among the mouse strains. These findings suggest that alpha-synuclein may contribute to impulsivity and potentially, to ICDs which arise in some PD patients treated with dopaminergic medication

On the mass radiated by coalescing black-hole binaries

We derive an analytic phenomenological expression that predicts the final mass of the black-hole remnant resulting from the merger of a generic binary system of black holes on quasi-circular orbits. Besides recovering the correct test-particle limit for extreme mass-ratio binaries, our formula reproduces well the results of all the numerical-relativity simulations published so far, both when applied at separations of a few gravitational radii, and when applied at separations of tens of thousands of gravitational radii. These validations make our formula a useful tool in a variety of contexts ranging from gravitational-wave physics to cosmology. As representative examples, we first illustrate how it can be used to decrease the phase error of the effective-one-body waveforms during the ringdown phase. Second, we show that, when combined with the recently computed self-force correction to the binding energy of nonspinning black-hole binaries, it provides an estimate of the energy emitted during the merger and ringdown. Finally, we use it to calculate the energy radiated in gravitational waves by massive black-hole binaries as a function of redshift, using different models for the seeds of the black-hole population.Comment: 9 pages (emulateapj), 4 figures. Matches version in ApJ but includes slight changes to fig 4 described in Barausse, et al ApJ 786, 76 (2014) (doi:10.1088/0004-637X/786/1/76), see also http://www2.iap.fr/users/barausse/erratum_mass_formula.pd

ALS-linked cytoplasmic FUS assemblies are compositionally different from physiological stress granules and sequester hnRNPA3, a novel modifier of FUS toxicity

Formation of cytoplasmic RNA-protein structures called stress granules (SGs) is a highly conserved cellular response to stress. Abnormal metabolism of SGs may contribute to the pathogenesis of (neuro)degenerative diseases such as amyotrophic lateral sclerosis (ALS). Many SG proteins are affected by mutations causative of these conditions, including fused in sarcoma (FUS). Mutant FUS variants have high affinity to SGs and also spontaneously form de novo cytoplasmic RNA granule

Kinetics of alpha-synuclein depletion in three brain regions following conditional pan-neuronal inactivation of the encoding gene (Snca) by tamoxifen-induced Cre-recombination in adult mice

Conditional pan-neuronal inactivation of the Snca gene in 2-month old male and female mice causes dramatic decrease in the level of the encoded protein, alpha-synuclein, in three studied brain regions, namely cerebral cortex, midbrain and striatum, 12 weeks after the last injection of tamoxifen. Kinetics of alpha-synuclein depletion is different in these brain regions with a longer lag period in the cerebral cortex where this protein is normally most abundant. Our results suggest that efficient post-developmental pan-neuronal knockout of alpha-synuclein in adult, i.e. 5- to 6-month old, animals, could be achieved by tamoxifen treatment of 2-month old mice carrying loxP-flanked Snca gene and expressing inducible Cre-ERT2 recombinase under control of the promoter of neuron-specific enolase (NSE) gene

Triple-knockout, synuclein-free mice display compromised lipid pattern

Recent studies have implicated synucleins in several reactions during the biosynthesis of lipids and fatty acids in addition to their recognised role in membrane lipid binding and synaptic functions. These are among aspects of decreased synuclein functions that are still poorly acknowledged especially in regard to pathogenesis in Parkinson’s disease. Here, we aimed to add to existing knowledge of synuclein deficiency (i.e., the lack of all three family members), with respect to changes in fatty acids and lipids in plasma, liver, and two brain regions in triple synuclein-knockout (TKO) mice. We describe changes of long-chain polyunsaturated fatty acids (LCPUFA) and palmitic acid in liver and plasma, reduced triacylglycerol (TAG) accumulation in liver and non-esterified fatty acids in plasma of synuclein free mice. In midbrain, we observed counterbalanced changes in the relative concentrations of phosphatidylcholine (PC) and cerebrosides (CER). We also recorded a notable reduction in ethanolamine plasmalogens in the midbrain of synuclein free mice, which is an important finding since the abnormal ether lipid metabolism usually associated with neurological disorders. In summary, our data demonstrates that synuclein deficiency results in alterations of the PUFA synthesis, storage lipid accumulation in the liver, and the reduction of plasmalogens and CER, those polar lipids which are principal compounds of lipid rafts in many tissues. An ablation of all three synuclein family members causes more profound changes in lipid metabolism than changes previously shown to be associated with γ-synuclein deficiency alone. Possible mechanisms by which synuclein deficiency may govern the reported modifications of lipid metabolism in TKO mice are proposed and discussed