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

Mesoscale dynamics on the Sun's surface from HINODE observations

Aims: The interactions of velocity scales on the Sun's surface, from granulation to supergranulation are still not understood, nor are their interaction with magnetic fields. We thus aim at giving a better description of dynamics in the mesoscale range which lies between the two scales mentioned above. Method: We analyse a 48h high-resolution time sequence of the quiet Sun photosphere at the disk center obtained with the Solar Optical Telescope onboard Hinode. The observations, which have a field of view of 100 \arcsec$\times$ 100 \arcsec, typically contain four supergranules. We monitor in detail the motion and evolution of granules as well as those of the radial magnetic field. Results: This analysis allows us to better characterize Trees of Fragmenting Granules issued from repeated fragmentation of granules, especially their lifetime statistics. Using floating corks advected by measured velocity fields, we show their crucial role in the advection of the magnetic field and in the build up of the network. Finally, thanks to the long duration of the time series, we estimate that the turbulent diffusion coefficient induced by horizontal motion is approximately $430 \mathrm{km}^2 \mathrm{s}^{-1}$. Conclusions: These results demonstrate that the long living families contribute to the formation of the magnetic network and suggest that supergranulation could be an emergent length scale building up as small magnetic elements are advected and concentrated by TFG flows. Our estimate for the magnetic diffusion associated with this horizontal motion might provide a useful input for mean-field dynamo models.Comment: to appear in A&A - 8 pages, 13 figures (degraded quality) - Full resolution version available @ http://www.ast.obs-mip.fr/users/rincon/hinode_roudier_aa09.pd

Perdas economicas decorrentes de diferentes graus de severidade e rinite atrofica em suinos.

bitstream/CNPSA/7661/1/cot169.pdf; bitstream/item/58760/1/CUsersPiazzonDocuments169.pd

Tiling the plane without supersymmetry

We present a way of tiling the plane with a regular hexagonal network of defects. The network is stable and follows in consequence of the three-junctions that appear in a model of two real scalar fields that presents $Z_3$ symmetry. The $Z_3$ symmetry is effective in both the vacuum and defect sectors, and no supersymmetry is required to build the network.Comment: Revtex, 4 pages, 1 ps figure; version to appear in Phys. Rev. Let

Problemas Actuales de Política Educacional en Chile, indagando en tiempo. Investigación Documental. ¿ Qué refleja el actual sistema de evalucación docente, como politica educativa, de la democracia chilena?

Trabajo presentado en la cátedra Política y Gestión Educacional en Chile, Magíster en política y gestión Educacional.Vivimos en una sociedad que ve a las formas evaluativas como parte de la realidad diaria. Dentro de este ámbito, la Evaluación Docente debería ser una más entre tantas, por lo que no tendría que llamar la atención más de lo que es en sí misma; sin embargo esto no sucede, puesto que no ha quedado lo suficientemente claro el tipo de evaluación que es, su finalidad como fortalecimiento, por una parte, de la profesión docente y por otra, su influencia directa, pero no exclusiva, en la calidad de la educación. No se debe dejar de lado su origen, el cual se gesta en un modelo de Democracia tan singular como lo es el modelo neoliberal de nuestra democracia, que pareciera tener más ribetes de una democracia más bien técnica, que una de carácter participativo. Bajo esta mirada, la Política de la Evaluación Docente se puede definir bajo dos ámbitos evaluativos: el democrático versus el tecno-evaluativo

18 Sco: a solar twin rich in refractory and neutron-capture elements. Implications for chemical tagging

We study with unprecedented detail the chemical composition and stellar parameters of the solar twin 18 Sco in a strictly differential sense relative to the Sun. Our study is mainly based on high resolution (R ~ 110 000) high S/N (800-1000) VLT UVES spectra, which allow us to achieve a precision of about 0.005 dex in differential abundances. The effective temperature and surface gravity of 18 Sco are Teff = 5823+/-6 K and log g = 4.45+/-0.02 dex, i.e., 18 Sco is 46+/-6 K hotter than the Sun and log g is 0.01+/-0.02 dex higher. Its metallicity is [Fe/H] = 0.054+/-0.005 dex and its microturbulence velocity is +0.02+/-0.01 km/s higher than solar. Our precise stellar parameters and differential isochrone analysis show that 18 Sco has a mass of 1.04+/-0.02M_Sun and that it is ~1.6 Gyr younger than the Sun. We use precise HARPS radial velocities to search for planets, but none were detected. The chemical abundance pattern of 18 Sco displays a clear trend with condensation temperature, showing thus higher abundances of refractories in 18 Sco than in the Sun. Intriguingly, there are enhancements in the neutron-capture elements relative to the Sun. Despite the small element-to-element abundance differences among nearby n-capture elements (~0.02 dex), we successfully reproduce the r-process pattern in the solar system. This is independent evidence for the universality of the r-process. Our results have important implications for chemical tagging in our Galaxy and nucleosynthesis in general.Comment: ApJ, in pres

Carbon (CI) and energy intensity (EI) dataset for retail stores

Transparency data associated with this article can be found in the online version at: https://doi.org/10.1016/j.dib.2018.10.080This data article presents data collected from the 250 highest revenue retailers around the world, assessed according to publicly available data from the fiscal year 2016, in order to determine retailer?s overall carbon intensity (CI) and energy intensity (EI). Data collection included additional variables such as retailers? revenue rank, operational typology, number of stores, store sales area and number of workers. CI and EI benchmarks were calculated for food and non-food retailers, applying the statistic function first quartile (Q1) for the best practice, second (Q2) and third (Q3) quartiles for conventional practice and fourth quartile (Q4) for worst practice. Correlations were tested between the variables "EI", "CI" and "retailer revenue", applying the statistic function CORREL. Finally, a cluster analysis was performed for food and non-food retailers, to identify possible segmentation patterns between the variables ?EI?, ?CI? and ?retailer revenue?. The information provided in this data article is useful for furthering research developments on the influence of isolated variables on retail EI and CI and in assisting retailers, architects, engineers, and policy makers in establishing optimal energy performance goals for the design and operation of retail stores. For further data interpretation and discussion, see the article ?Combined carbon and energy intensity benchmarks for sustainable retail stores?[1], of the same authors.This work was supported by FCT - Fundação para a Ciência e Tecnologia [grant number PD/BD/127852/2016] under the Doctoral Program EcoCoRe - Eco-Construction and Rehabilitation.info:eu-repo/semantics/publishedVersio

Combined carbon and energy intensity benchmarks for sustainable retail stores

Retail stores are amongst the building typologies with the highest carbon (CI) and energy intensities (EI). However, previous studies have only explored the EI of food and non-food retailers. This study is the first of its kind to examine the link between CI and EI. Establishing the nature of this link will allow a deeper understanding of how to decarbonize the retail sector. Here, we hypothesised whether in retail low EI correlated with low CI and how corporate revenue affected these variables. ?Best practice? and ?conventional practice? benchmarks were then developed to assess retail buildings' sustainability. These represent missing and highly desirable tools in retail sustainable management. Average EI and CI of food retailers were twice that of non-food retailers (EI-548 vs 238?kWh/m2/y; CI266 vs 132?kg CO?eq/m2/y). The correlation found between EI and CI indicates that low energy consumption leads to low greenhouse gas (GHG) emissions. CI variability resulted mostly of energy-efficiency strategies, of the energy production process and of GHG emissions from refrigeration systems. EI variability resulted mostly from store typology, volume and usage. The proposed benchmarks help to set energy and carbon reference performance levels in retail buildings and to stimulate best sustainable practice amongst retailers.This work was supported by FCT - Fundação para a Ciência e Tecnologia [grant number PD/BD/127852/2016] under the Doctoral Program EcoCoRe - Eco-Construction and Rehabilitation. Support from CERIS and Instituto Superior Técnico is also acknowledged.info:eu-repo/semantics/publishedVersio