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

Positive zeta potential of nanodiamonds

In this paper, the origin of positive zeta potential exhibited by nanodiamond particles is explained. Positive zeta potentials in nano-structured carbons can be explained by the presence of graphitic planes at the surface, which leave oxygen-free Lewis sites and so promotes the suppression of acidic functional groups. Electron Microscopy and Raman Spectroscopy have been used to show that positive zeta potential of nanodiamond is only exhibited in the presence of sp2 carbon at the surface

Practicing Conscious Architectural Experience

The procedural exercise of practicing Conscious Architectural Experience (CAE) was first authored by Julio Bermudez, Professor of Architecture at Catholic University of America, as a means of engaging an architectural work that requires the suspension of the critical mind and preferences the embodied experience. The premise is that through slowness and openness one might more fully understand and comprehend a work of architecture. While the practice of CAE was originally intended to be building focused, this paper expands this practice to engage places and project sites

Standardizing Documentation of Patients’ Measurable Decline to Increase Medicare Compliance in the Hospice Setting

Problem: Staff nurses have difficulties standardizing documentation of patients’ measurable decline during the admission and recertification process to justify the need for hospice services. Context: According to Murrin (2016), the average Medicare compliance rate of hospice organizations is 86%. This quality improvement (QI) project aims to increase an outpatient hospice organization’s Medicare compliance rate of 66% to the average, nationwide level through standardization of documentation (Frontz, 2021). Interventions: The proposed intervention is to implement a QI project of the following assessment tools: Palliative Performance Scale (PPS), Functional Assessment Staging Tool (FAST) and Mid-Upper Arm Circumference (MUAC). Clinical nurses will attend a one–hour training class on tool implementation. Measures Post implementation, bi-weekly chart audits were conducted over the course of three months. In addition, bi-weekly check-ins were conducted at staff meetings to answer any questions and provide opportunities for feedback. Results The quality report revealed that of the 84 admission notes audited, 78 notes were found to include the three proposed assessment tools. Thus resulting in a successful implementation rate of 88.6%. Conclusions Given the actual implementation rate was 2.6% higher than the project goal of 86%, the assessment tool bundle may be useful in thorough, standardized hospice documentation. Moving forward, further research is necessary in other hospice organizations to correlate the assessment tool findings and mortality rates

Central Pb+Pb Collisions at 158 A GeV/c Studied by Pion-Pion Interferometry

Two-particle correlations have been measured for identified negative pions from central 158 AGeV Pb+Pb collisions and fitted radii of about 7 fm in all dimensions have been obtained. A multi-dimensional study of the radii as a function of kT is presented, including a full correction for the resolution effects of the apparatus. The cross term Rout-long of the standard fit in the Longitudinally CoMoving System (LCMS) and the vl parameter of the generalised Yano-Koonin fit are compatible with 0, suggesting that the source undergoes a boost invariant expansion. The shapes of the correlation functions in Qinv and Qspace have been analyzed in detail. They are not Gaussian but better represented by exponentials. As a consequence, fitting Gaussians to these correlation functions may produce different radii depending on the acceptance of the experimental setup used for the measurement.Comment: 13 pages including 10 figure

Higher education and unemployment in Europe : an analysis of the academic subject and national effects

This paper examines the impact of an academic degree and field of study on short and long-term unemployment across Europe (EU15). Labour Force Survey (LFS) data on over half a million individuals are utilised for that purpose. The harmonized LFS classification of level of education and field of study overcomes past problems of comparability across Europe. The study analyses (i) the effect of an academic degree at a European level, (ii) the specific effect of 14 academic subjects and (iii) country specific effects. The results indicate that an academic degree is more effective on reducing the likelihood of short-term than long-term unemployment. This general pattern even though it is observed for most of the academic subjects its levels show significant variation across disciplines and countries

Proximity effect at superconducting Sn-Bi2Se3 interface

We have investigated the conductance spectra of Sn-Bi2Se3 interface junctions down to 250 mK and in different magnetic fields. A number of conductance anomalies were observed below the superconducting transition temperature of Sn, including a small gap different from that of Sn, and a zero-bias conductance peak growing up at lower temperatures. We discussed the possible origins of the smaller gap and the zero-bias conductance peak. These phenomena support that a proximity-effect-induced chiral superconducting phase is formed at the interface between the superconducting Sn and the strong spin-orbit coupling material Bi2Se3.Comment: 7 pages, 8 figure

System Size and Energy Dependence of Jet-Induced Hadron Pair Correlation Shapes in Cu+Cu and Au+Au Collisions at sqrt(s_NN) = 200 and 62.4 GeV

We present azimuthal angle correlations of intermediate transverse momentum (1-4 GeV/c) hadrons from {dijets} in Cu+Cu and Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is broadened, non-Gaussian, and peaked away from \Delta\phi=\pi in central and semi-central collisions in all the systems. The broadening and peak location are found to depend upon the number of participants in the collision, but not on the collision energy or beam nuclei. These results are consistent with sound or shock wave models, but pose challenges to Cherenkov gluon radiation models.Comment: 464 authors from 60 institutions, 6 pages, 3 figures, 2 tables. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm