Mutant huntingtin enhances activation of dendritic Kv4 K+ channels in striatal spiny projection neurons

Huntington\u27s disease (HD) is initially characterized by an inability to suppress unwanted movements, a deficit attributable to impaired synaptic activation of striatal indirect pathway spiny projection neurons (iSPNs). To better understand the mechanisms underlying this deficit, striatal neurons in ex vivo brain slices from mouse genetic models of HD were studied using electrophysiological, optical and biochemical approaches. Distal dendrites of iSPNs from symptomatic HD mice were hypoexcitable, a change that was attributable to increased association of dendritic Kv4 potassium channels with auxiliary KChIP subunits. This association was negatively modulated by TrkB receptor signaling. Dendritic excitability of HD iSPNs was rescued by knocking-down expression of Kv4 channels, by disrupting KChIP binding, by restoring TrkB receptor signaling or by lowering mutant-Htt (mHtt) levels with a zinc finger protein. Collectively, these studies demonstrate that mHtt induces reversible alterations in the dendritic excitability of iSPNs that could contribute to the motor symptoms of HD

UV Spectral Synthesis of Vega

We show that the UV spectrum (1280-3200 A) of the "superficially normal" A-star Vega, as observed by the IUE satellite at a resolution comparable to the star's rotational broadening width, can be fit remarkably well by a single-temperature synthetic spectrum based on LTE atmosphere models and a newly constructed UV line list. If Vega were a normal, equator-on, slow-rotating star, then its spectrum and our analysis would indicate a temperature of Teff ~ 9550 K, surface gravity of log g ~ 3.7, general surface metallicity of [m/H] ~ -0.5, and a microturbulence velocity of v(turb) ~ 2.0 km/s. Given its rapid rotation and nearly pole-on orientation, however, these parameters must be regarded as representing averages across the observed hemisphere. Modeling the complex UV line spectrum has allowed us to determine the specific surface abundances for 17 different chemical elements, including CNO, the light metals, and the iron group elements. The resultant abundance pattern agrees in general with previous results, although there is considerable scatter in the literature. Despite its peculiarities, Vega has turned out to provide a powerful test of the extent of our abilities to model the atmospheric properties of the early A-stars, particularly the detailed UV line spectrum. The value of the measurements from this pilot study will increase as this analysis is extended to more objects in the rich high-dispersion IUE data archive, including both normal and peculiar objects.Comment: To appear in the Astrophysical Journa

HD 51106 and HD 50747: an ellipsoidal binary and a triple system observed with CoRoT

We present an analysis of the observations of HD 51106 and HD 50747 by the satellite CoRoT, obtained during its initial run, and of the spectroscopic preparatory observations. AIMS: We complete an analysis of the light curve, extract the main frequencies observed, and discuss some preliminary interpretations about the stars. Methods: We used standard Fourier transform and pre-whitening methods to extract information about the periodicities of the stars. Results: HD 51106 is an ellipsoidal binary, the light curve of which can be completely explained by the tidal deformation of the star and smaller secondary effects. HD 50747 is a triple system containing a variable star, which exhibits many modes of oscillation with periods in the range of a few hours. On the basis of this period range and the analysis of the physical parameters of the star, we conclude that HD 50747 is a Gamma-Doradus star.Comment: 7 pages, 8 figures, use (Astronomy-Astrophysics format/macro LAtex

Four-colour photometry of eclipsing binaries. XL, uvby light curves for the B-type systems DW Carinae, BF Centauri, AC Velorum, and NSV 5783

Aims. In order to increase the limited number of B-stars with accurately known dimensions, and also the number of well studied eclipsing binaries in open clusters, we have undertaken observations and studies of four southern double-lined eclipsing B-type binaries; DWCar, BF Cen, ACVel, and NSV 5783. Methods. Complete uvby light curves were observed between January 1982 and April 1991 at the Danish 0.5 m telescope at ESO La Silla, since 1985 known as the Strömgren Automatic Telescope (SAT). Standard indices for the systems and the comparison stars,as well as additional minima observations for ACVel, have been obtained later at SAT. For DWCar and ACVel, high-resolution spectra for definitive spectroscopic orbits have also been obtained; they are presented as part of the detailed analyses of these systems. A few spectra of NSV 5783 are included in the present paper. Results. For all four systems, the first modern accurate light curves have been established. DWCar is a detached system consisting of two nearly identical components. It is member of the young open cluster Cr228. A detailed analysis, based on the new light curves and 29 high-resolution spectra, is published separately. BFCen is semidetached and is member of NGC 3766. Modern spectra are needed for a detailed study. ACVel is a detached system with at least one more star. A full analysis, based on the new light curves and 18 high-resolution spectra, is published separately. NSV 5783 is discovered to be an eclipsing binary consisting of two well-detached components in an 11-day period eccentric (e = 0.18) orbit. Secondary eclipse is practically total. From the light curves and a few high-resolution spectra, accurate photometric elements and preliminary absolute dimensions have been determined. The quite similar components have masses of about 5 M and radii of about 3.5 R, and they seem to have evolved just slightly off the ZAMS. The measured rotational velocities (≈150 km s−1) are about 6 times those corresponding to pseudosynchronization

The effect of rotation on the spectrum of Vega

The discovery that Vega is a rapidly rotating pole-on star has raised a number of questions about this fundamental standard, including such issues as its composition, and in turn its mass and age. We report here a reanalysis of Vega's composition. A full spectral synthesis based on the Roche model derived earlier from NPOI interferometry is used. We find the line shapes in Vega's spectrum to be more complex than just flat-bottomed, which have been previously reported; profiles range from slightly self-reversed to simple ``V'' shapes. A high SNR spectrum, obtained by stacking spectra from the ELODIE archive, shows excellent agreement with the calculations, provided we add about 10 km/s of macroturbulence to the predicted spectra. From the abundance analysis, we find that Vega shows the peculiar abundance pattern of a \W Bootis star as previously suggested. We investigate the effects of rotation on the deduced abundances and show that the dominant ionization states are only slightly affected compared to analyses using non-rotating models. We argue that the rapid rotation requires the star be fully mixed. The composition leads to masses and particularly ages that are quite different compared to what are usually assumed.Comment: 16 pages, 4 figures, accepted by Ap

Bounded excursion stable gravastars and black holes

Dynamical models of prototype gravastars were constructed in order to study their stability. The models are the Visser-Wiltshire three-layer gravastars, in which an infinitely thin spherical shell of stiff fluid divides the whole spacetime into two regions, where the internal region is de Sitter, and the external is Schwarzschild. It is found that in some cases the models represent the "bounded excursion" stable gravastars, in which the thin shell is oscillating between two finite radii, while in other cases they collapse until the formation of black holes. In the phase space, the region for the ``bounded excursion" gravastars is very small in comparison to that of black holes, but not empty. Therefore, although the existence of gravastars cannot be excluded from such dynamical models, our results do indicate that, even if gravastars indeed exist, they do not exclude the existence of black holes.Comment: Revtex4, 12 figures. Version published in JCAP, 06 (2008) 02

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

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The ongoing pursuit of neuroprotective therapies in Parkinson disease

Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD

The eccentric massive binary V380 Cyg: revised orbital elements and interpretation of the intrinsic variability of the primary component

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