Imbalance of p75(NTR)/TrkB protein expression in Huntington's disease: Implication for neuroprotective therapies

Neuroprotective therapies based on brain-derived neurotrophic factor (BDNF) administration have been proposed for Huntington's disease (HD) treatment. However, our group has recently reported reduced levels of TrkB in HD mouse models and HD human brain suggesting that besides a decrease on BDNF levels a reduction of TrkB expression could also contribute to diminished neurotrophic support in HD. BDNF can also bind to p75 neurotrophin receptor (p75(NTR)) modulating TrkB signaling. Therefore, in this study we have analyzed the levels of p75(NTR) in several HD models, as well as in HD human brain. Our data demonstrates a p75(NTR)/TrkB imbalance in the striatum of two different HD mouse models, Hdh(Q111/111) homozygous knockin mice and R6/1 mice that was also manifested in the putamen of HD patients. The imbalance between TrkB and p75(NTR) levels in a HD cellular model did not affect BDNF-mediated TrkB activation of prosurvival pathways but induced activation of apoptotic cascades as demonstrated by increased JNK phosphorylation. Moreover, BDNF failed to protect mutant huntingtin striatal cells transfected with p75(NTR) against NMDA-mediated excitotoxicity, which was associated with decreased Akt phosphorylation. Interestingly, lack of Akt activation following BDNF and NMDA treatment correlated with increased PP1 levels. Accordingly, pharmacological inhibition of PP1 by okadaic acid (OA) prevented mutant huntingtin striatal cell death induced by NMDA and BDNF. Altogether, our findings demonstrate that the p75(NTR)/TrkB imbalance induced by mutant huntingtin in striatal cells associated with the aberrant activity of PP1 disturbs BDNF neuroprotection likely contributing to increasing striatal vulnerability in HD. On the basis of this data we hypothesize that normalization of p75(NTR) and/or TrkB expression or their signaling will improve BDNF neuroprotective therapies in HD. Cell Death and Disease (2013) 4, e595; doi:10.1038/cddis.2013.116; published online 18 April 201

Structure, phase transformations, and defects of HfO₂ and ZrO₂ nanoparticles studied by ^(181)Ta and ^(111)Cd perturbed angular correlations, ^(1) H magic-angle spinning NMR, XPS, and x-ray and electron diffraction

Structure, phase transformations, grain growth, and defects of bare and alumina-coated nanoparticles of HfO₂ and ZrO₂ synthesized in a microwave-plasma process have been investigated by x-ray diffraction (XRD), transmission electron microscopy (TEM), and perturbed angular correlation (PAC) spectroscopy. The PAC technique was used to measure the electric quadrupole interactions (QIs) of the nuclear probes ^(181)Ta and ^(111)Cd in nanocrystalline HfO₂ and ZrO₂ as a function of temperature. For comparison, the QI of ^(181)Ta in the bulk oxides was determined in the same temperature range 300 K ≤ T ≤ 1550 K. The oxygen-metal ratio of the as- ynthesized particles was determined by x-ray photoelectron spectroscopy to be in the range 1.4 ≤ x ≤ 1.8. A hydrate surface layer with a hydrogen content of 5–10 wt %, consisting of chemisorbed hydroxyl groups and organic precursor fragments, was detected by ^(1) H magic-angle spinning NMR. XRD and TEM show that bare n-ZrO₂, Al₂O₃-coated n-ZrO₂, and Al₂O₃-coated n-HfO₂ are synthesized in the tetragonal or cubic modification with a particle size d < 5 nm, whereas bare n-HfO₂ is mainly monoclinic. The grain growth activation enthalpy of bare n-ZrO₂ is Q_(A)=32(5)kJ/mol. Coating with Al₂O₃ stabilizes the tetragonal over the monoclinic phase, both in hafnia and zirconia nanoparticles. While TEM micrographs of the native nanoparticles reveal a well-ordered cation sublattice, the observation of a broad QI distribution in the PAC spectra suggests a high degree of disorder of the oxygen sublattice. The gradual transformation of the disordered state and the phase evolution were studied by high-temperature QI measurements. Hafnia nanoparticles persist in the monoclinic (m) phase up to T ≤ 1400 K. In coated n-ZrO₂ /Al₂O₃, the monoclinic and tetragonal (t) phases coexist over a large temperature range, whereas uncoated, initially tetragonal or cubic (t or c) n-ZrO₂ presents a sharp m↔t transition. A “defect” component involving 30%–40% of the probe nuclei appears in the ^(181)Ta PAC spectra of all nanoparticles when these are cooled from high temperatures T ≥ 1200 K. The temperature dependence of this component can be reproduced by assuming that Ta impurities in hafnia and zirconia may trap electrons at low temperatures. The observation that the defect component appears only in nanoparticles with diameter d < 100 nm suggests that mobile electrons are available only in the surface region of the oxide particles, either from oxygen vacancies (Vo) and/or Vo- hydrogen donors at the interface of the nanoparticles and their hydrate layers. This conclusion is supported by the absence of a size effect for ^(111)Cd probes in HfO₂ and ZrO₂. The temperature dependence of the ^(181)Ta defect fraction is consistent with a Ta_(+) impurity level at E_d ~ 0.9 and 0.6 eV below the hafnia and zirconia conduction band, respectively

Temporal evolution of the Evershed flow in sunspots. II. Physical properties and nature of Evershed clouds

Context: Evershed clouds (ECs) represent the most conspicuous variation of the Evershed flow in sunspot penumbrae. Aims: We determine the physical properties of ECs from high spatial and temporal resolution spectropolarimetric measurements. Methods: The Stokes profiles of four visible and three infrared spectral lines are subject to inversions based on simple one-component models as well as more sophisticated realizations of penumbral flux tubes embedded in a static ambient field (uncombed models). Results: According to the one-component inversions, the EC phenomenon can be understood as a perturbation of the magnetic and dynamic configuration of the penumbral filaments along which these structures move. The uncombed inversions, on the other hand, suggest that ECs are the result of enhancements in the visibility of penumbral flux tubes. We conjecture that the enhancements are caused by a perturbation of the thermodynamic properties of the tubes, rather than by changes in the vector magnetic field. The feasibility of this mechanism is investigated performing numerical experiments of thick penumbral tubes in mechanical equilibrium with a background field. Conclusions: While the one-component inversions confirm many of the properties indicated by a simple line parameter analysis (Paper I of this series), we tend to give more credit to the results of the uncombed inversions because they take into account, at least in an approximate manner, the fine structure of the penumbra.Comment: Accepted for publication in A&

Prompt dipole radiation in fusion reactions

The prompt gamma ray emission was investigated in the 16A MeV energy region by means of the 36,40Ar+96,92Zr fusion reactions leading to a compound nucleus in the vicinity of 132Ce. We show that the prompt radiation, which appears to be still effective at such a high beam energy, has an angular distribution pattern consistent with a dipole oscillation along the symmetry axis of the dinuclear system. The data are compared with calculations based on a collective bremsstrahlung analysis of the reaction dynamics

Strategy for the inversion of Hinode spectropolarimetric measurements in the quiet Sun

In this paper we propose an inversion strategy for the analysis of spectropolarimetric measurements taken by {\em Hinode} in the quiet Sun. The spectropolarimeter of the Solar Optical Telescope aboard {\em Hinode} records the Stokes spectra of the \ion{Fe}{i} line pair at 630.2 nm with unprecendented angular resolution, high spectral resolution, and high sensitivity. We discuss the need to consider a {\em local} stray-light contamination to account for the effects of telescope diffraction. The strategy is applied to observations of a wide quiet Sun area at disk center. Using these data we examine the influence of noise and initial guess models in the inversion results. Our analysis yields the distributions of magnetic field strengths and stray-light factors. They show that quiet Sun internetwork regions consist mainly of hG fields with stray-light contaminations of about 0.8.Comment: To appear in Publications of the Astronomical Society of Japan, 8 pages, 10 figure

Autonomous on-board data processing and instrument calibration software for the SO/PHI

The extension of on-board data processing capabilities is an attractive option to reduce telemetry for scientific instruments on deep space missions. The challenges that this presents, however, require a comprehensive software system, which operates on the limited resources a data processing unit in space allows. We implemented such a system for the Polarimetric and Helioseismic Imager (PHI) on-board the Solar Orbiter (SO) spacecraft. It ensures autonomous operation to handle long command-response times, easy changing of the processes after new lessons have been learned and meticulous book-keeping of all operations to ensure scientific accuracy. This contribution presents the requirements and main aspects of the software implementation, followed by an example of a task implemented in the software frame, and results from running it on SO/PHI. The presented example shows that the different parts of the software framework work well together, and that the system processes data as we expect. The flexibility of the framework makes it possible to use it as a baseline for future applications with similar needs and limitations as SO/PHI.Comment: Conference: SPIE Astronomical Telescopes + Instrumentatio, Software and Cyberinfrastructure for Astronomy

Relativistic MHD Simulations of Jets with Toroidal Magnetic Fields

This paper presents an application of the recent relativistic HLLC approximate Riemann solver by Mignone & Bodo to magnetized flows with vanishing normal component of the magnetic field. The numerical scheme is validated in two dimensions by investigating the propagation of axisymmetric jets with toroidal magnetic fields. The selected jet models show that the HLLC solver yields sharper resolution of contact and shear waves and better convergence properties over the traditional HLL approach.Comment: 12 pages, 5 figure

Vector spectropolarimetry of dark-cored penumbral filaments with Hinode

We present spectropolarimetric measurements of dark-cored penumbral filaments taken with Hinode at a resolution of 0.3". Our observations demonstrate that dark-cored filaments are more prominent in polarized light than in continuum intensity. Far from disk center, the Stokes profiles emerging from these structures are very asymmetric and show evidence for magnetic fields of different inclinations along the line of sight, together with strong Evershed flows of at least 6-7 km/s. In sunspots closer to disk center, dark-cored penumbral filaments exhibit regular Stokes profiles with little asymmetries due to the vanishing line-of-sight component of the horizontal Evershed flow. An inversion of the observed spectra indicates that the magnetic field is weaker and more inclined in the dark cores as compared with the surrounding bright structures. This is compatible with the idea that dark-cored filaments are the manifestation of flux tubes carrying hot Evershed flows.Comment: Accepted for publication in ApJ Letters. Use the Postscript version for high quality figure

Moving Magnetic Features around a Pore

Spectropolarimetric observations from Sunrise II/IMaX obtained in June 2013 are used for a statistical analysis to determine the physical properties of moving magnetic features (MMFs) observed near a pore. MMFs of the same and opposite polarity with respect to the pore are found to stream from its border at an average speed of 1.3 km s$^{-1}$ and 1.2 km s$^{-1}$ respectively, with mainly same-polarity MMFs found further away from the pore. MMFs of both polarities are found to harbor rather weak, inclined magnetic fields. Opposite-polarity MMFs are blue-shifted, while same-polarity MMFs do not show any preference for up- or downflows. Most of the MMFs are found to be of sub-arcsecond size and carry a mean flux of $\sim$ 1.2$\times 10^{17}$ Mx.Comment: 8 pages, 4 figures, accepted for publication in ApJ