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

Moving magnetic features around a pore

A. J. Kaithakkal et. al.©2017 The American Astronomical Society. All rights reserved.Spectropolarimetric observations from Sunrise/IMaX, obtained in 2013 June, 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 blueshifted, whereas 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 ~1.2 × 1017 Mx.The German contribution to Sunrise and its reflight was funded by the Max Planck Foundation, the Strategic Innovations Fund of the President of the Max Planck Society (MPG), DLR, and private donations by supporting members of the Max Planck Society, which is gratefully acknowledged. The Spanish contribution was funded by the Ministerio de Economía y Competitividad under Projects ESP2013-47349-C6 and ESP2014-56169-C6, partially using European FEDER funds. The HAO contribution was partly funded through NASA grant number NNX13AE95G. This work was partly supported by the BK21 plus program through the National Research Foundation (NRF) funded by the Ministry of Education of Korea.Peer reviewe

SUNRISE/IMaX observations of convectively driven vortex flows in the Sun

We characterize the observational properties of the convectively driven vortex flows recently discovered on the quiet Sun, using magnetograms, Dopplergrams and images obtained with the 1-m balloon-borne Sunrise telescope. By visual inspection of time series, we find some 3.1e-3 vortices/(Mm^2 min), which is a factor of 1.7 larger than previous estimates. The mean duration of the individual events turns out to be 7.9 min, with a standard deviation of 3.2 min. In addition, we find several events appearing at the same locations along the duration of the time series (31.6 min). Such recurrent vortices show up in the proper motion flow field map averaged over the time series. The typical vertical vorticities are <= 6e-3 1/sec, which corresponds to a period of rotation of some 35 min. The vortices show a preferred counterclockwise sense of rotation, which we conjecture may have to do with the preferred vorticity impinged by the solar differential rotation.Comment: To appear in ApJL. 5 Figs, 4 pages. The two animations associated with the work can be downloaded from http://www.iac.es/proyecto/solarhr/imaxvortex.html References updated in V

First high-resolution images of the Sun in the 2796 \AA{} Mg II k line

We present the first high-resolution solar images in the Mg II k 2796 \AA{} line. The images, taken through a 4.8 \AA{} broad interference filter, were obtained during the second science flight of SUNRISE in June 2013 by the SuFI instrument. The Mg II k images display structures that look qualitatively very similar to images taken in the core of Ca II H. The Mg II images exhibit reversed granulation (or shock waves) in the internetwork regions of the quiet Sun, at intensity contrasts that are similar to those found in Ca II H. Very prominent in Mg II are bright points, both in the quiet Sun and in plage regions, particularly near disk center. These are much brighter than at other wavelengths sampled at similar resolution. Furthermore, Mg II k images also show fibril structures associated with plage regions. Again, the fibrils are similar to those seen in Ca II H images, but tend to be more pronounced, particularly in weak plage.Comment: Accepted for publication in The Astrophysical Journal Letter

Applicability of Milne-Eddington inversions to high spatial resolution observations of the quiet Sun

The physical conditions of the solar photosphere change on very small spatial scales both horizontally and vertically. Such a complexity may pose a serious obstacle to the accurate determination of solar magnetic fields. We examine the applicability of Milne-Eddington (ME) inversions to high spatial resolution observations of the quiet Sun. Our aim is to understand the connection between the ME inferences and the actual stratifications of the atmospheric parameters. We use magnetoconvection simulations of the solar surface to synthesize asymmetric Stokes profiles such as those observed in the quiet Sun. We then invert the profiles with the ME approximation. We perform an empirical analysis of the heights of formation of ME measurements and analyze the uncertainties brought about by the ME approximation. We also investigate the quality of the fits and their relationship with the model stratifications. The atmospheric parameters derived from ME inversions of high-spatial resolution profiles are reasonably accurate and can be used for statistical analyses of solar magnetic fields, even if the fit is not always good. We also show that the ME inferences cannot be assigned to a specific atmospheric layer: different parameters sample different ranges of optical depths, and even the same parameter may trace different layers depending on the physical conditions of the atmosphere. Despite this variability, ME inversions tend to probe deeper layers in granules as compared with intergranular lanes.Comment: Accepted for publication in Astronomy and Astrophysic

Fully resolved quiet-Sun magnetic flux tube observed with the Sunrise IMaX instrument

Until today, the small size of magnetic elements in quiet Sun areas has required the application of indirect methods, such as the line-ratio technique or multi-component inversions, to infer their physical properties. A consistent match to the observed Stokes profiles could only be obtained by introducing a magnetic filling factor that specifies the fraction of the observed pixel filled with magnetic field. Here, we investigate the properties of a small magnetic patch in the quiet Sun observed with the IMaX magnetograph on board the balloon-borne telescope Sunrise with unprecedented spatial resolution and low instrumental stray light. We apply an inversion technique based on the numerical solution of the radiative transfer equation to retrieve the temperature stratification and the field strength in the magnetic patch. The observations can be well reproduced with a one-component, fully magnetized atmosphere with a field strength exceeding 1 kG and a significantly enhanced temperature in the mid- to upper photosphere with respect to its surroundings, consistent with semi-empirical flux tube models for plage regions. We therefore conclude that, within the framework of a simple atmospheric model, the IMaX measurements resolve the observed quiet-Sun flux tube.Comment: Accepted for publication in The Astrophysical Journal Letters on Aug 11 201