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

Comment on “Nature and entropy content of the ordering transitions in RCo₂”

In their analysis of our perturbed angular correlation (PAC) study of the magnetic phase transitions of RCo₂ [Phys. Rev. B 68, 014409 (2003)], Herrero-Albillos [Phys. Rev. B 73, 134410 (2006)] come to the conclusion that it is very difficult for PAC spectroscopy to distinguish a first-order from a second-order phase transition. The statement is incorrect and does not resolve the conflict between the conclusion drawn from the PAC data and the differential scanning calorimetry data of Herrero- Albillos on the order of the magnetic phase transitions of PrCo₂ and NdCo₂. In this Comment we show that measurements of hyperfine interactions by PAC and other microscopic techniques are a very powerful tool for the investigation of phase transitions which may provide details on the transition not accessible to macroscopic methods. We explain why the PAC data leave no alternative to the conclusion that the spontaneous magnetization of PrCo₂ and NdCo₂ undergoes a discontinuous, first-order phase transition at T_(C)

Photospheric response to an ellerman bomb-like event—an analogy of Sunrise/IMaX observations and MHD simulations

S. Danilovic et. al.©2017 The American Astronomical Society. All rights reserved.Ellerman Bombs are signatures of magnetic reconnection, which is an important physical process in the solar atmosphere. How and where they occur is a subject of debate. In this paper, we analyze Sunrise/IMaX data, along with 3D MHD simulations that aim to reproduce the exact scenario proposed for the formation of these features. Although the observed event seems to be more dynamic and violent than the simulated one, simulations clearly confirm the basic scenario for the production of EBs. The simulations also reveal the full complexity of the underlying process. The simulated observations show that the Fe i 525.02 nm line gives no information on the height where reconnection takes place. It can only give clues about the heating in the aftermath of the reconnection. However, the information on the magnetic field vector and velocity at this spatial resolution is extremely valuable because it shows what numerical models miss and how they can be improved.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 are all gratefully acknowledged. This work has benefited from the discussions at the meeting "Solar UV bursts—a new insight to magnetic reconnection" at the International Space Science Institute (ISSI) in Bern. The Spanish contribution was funded by the Ministerio de Economia 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. The National Solar Observatory (NSO) is operated by the Association of Universities for Research in Astronomy (AURA) Inc. under a cooperative agreement with the National Science Foundation. This work was also partly supported by the BK21 plus program through the National Research Foundation (NRF), funded by the Ministry of Education of Korea.Peer reviewe

A tale of two emergences: Sunrise II observations of emergence sites in a solar active region

R. Centeno et. al.©2017 The American Astronomical Society. All rights reserved. In 2013 June, the two scientific instruments on board the second Sunrise mission witnessed, in detail, a small-scale magnetic flux emergence event as part of the birth of an active region. The Imaging Magnetograph Experiment (IMaX) recorded two small ($\sim 5^{\prime\prime}$) emerging flux patches in the polarized filtergrams of a photospheric Fe i spectral line. Meanwhile, the Sunrise Filter Imager (SuFI) captured the highly dynamic chromospheric response to the magnetic fields pushing their way through the lower solar atmosphere. The serendipitous capture of this event offers a closer look at the inner workings of active region emergence sites. In particular, it reveals in meticulous detail how the rising magnetic fields interact with the granulation as they push through the Sun's surface, dragging photospheric plasma in their upward travel. The plasma that is burdening the rising field slides along the field lines, creating fast downflowing channels at the footpoints. The weight of this material anchors this field to the surface at semi-regular spatial intervals, shaping it in an undulatory fashion. Finally, magnetic reconnection enables the field to release itself from its photospheric anchors, allowing it to continue its voyage up to higher layers. This process releases energy that lights up the arch-filament systems and heats the surrounding chromosphere.The National Center for Atmospheric Research is sponsored by the National Science Foundation.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

Magneto-static modeling from Sunrise/IMaX: application to an active region observed with Sunrise II

T. Wiegelmann et. al.©2017 The American Astronomical Society. All rights reserved.Magneto-static models may overcome some of the issues facing force-free magnetic field extrapolations. So far they have seen limited use and have faced problems when applied to quiet-Sun data. Here we present a first application to an active region. We use solar vector magnetic field measurements gathered by the IMaX polarimeter during the flight of the Sunrise balloon-borne solar observatory in 2013 June as boundary conditions for a magneto-static model of the higher solar atmosphere above an active region. The IMaX data are embedded in active region vector magnetograms observed with SDO/HMI. This work continues our magneto-static extrapolation approach, which was applied earlier to a quiet-Sun region observed with Sunrise I. In an active region the signal-to-noise-ratio in the measured Stokes parameters is considerably higher than in the quiet-Sun and consequently the IMaX measurements of the horizontal photospheric magnetic field allow us to specify the free parameters of the model in a special class of linear magneto-static equilibria. The high spatial resolution of IMaX (110–130 km, pixel size 40 km) enables us to model the non-force-free layer between the photosphere and the mid-chromosphere vertically by about 50 grid points. In our approach we can incorporate some aspects of the mixed beta layer of photosphere and chromosphere, e.g., taking a finite Lorentz force into account, which was not possible with lower-resolution photospheric measurements in the past. The linear model does not, however, permit us to model intrinsic nonlinear structures like strongly localized electric currents.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. The used HMI-data are courtesy of NASA/SDO and the HMI science team. TW acknowledges DLR-grant 50 OC 1301 and DFG-grant WI 3211/4-1. T.N. acknowledges support by the UK's Science and Technology Facilities Council via Consolidated Grants ST/K000950/1 and ST/N000609/1. D.N. was supported from GA ČR under grant numbers 16-05011S and 16-13277S. The Astronomical Institute Ondřejov is supported by the project RVO:67985815.Peer reviewe

Perturbed angular correlation study of the magnetic phase transitions in the rare-earth cobalt Laves phases RCo₂

The order and other properties of the magnetic phase transitions in the rare-earth (R)-cobalt Laves phases RCo2 have been studied for R=Gd, Tb, Dy, Ho, Er, Sm, Nd, and Pr by measuring the temperature dependence of the magnetic hyperfine interaction of the nuclear probe ^111Cdon the cubic R sites using the perturbed angular correlation technique. Both for heavy and light R constituents the transitions change from second order (Gd, Tb, Sm) to first order (Dy, Ho, Er, Nd, Pr) at order temperatures of 150-200 K. For heavy R constituents, the order deduced from the hyperfine interaction is in agreement with previous investigations. The observation of first order transitions in NdCo₂ and PrCo₂, however, is unexpected. In earlier studies the transitions in these compounds are usually classified as second order transitions. Both in the heavy and the light RCo₂ the discontinuous jump of the hyperfine interaction at the first order transitions increases with decreasing order temperature. This trend implies that the Co magnetization at the transition increases with decreasing T_C which can be related to the temperature dependence of the coefficient of the M^(4) term of the free energy in the Wohlfarth-Rhodes-Shimizu theory of itinerant electron magnetism. All compounds investigated presented a spread of the order temperature of similar to1-2 K which results in a coexistence of the paramagnetic and the magnetically ordered phase near the transition and causes a critical increase of the relative linewidth of the hyperfine frequency diverging as δ ∞ [(1-T/T_(C)]^ε with ε =-1.0(1)