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 forHuntington's disease (HD) treatment. However, our group has recently reported reduced levels of TrkB in HD mouse models andHD human brain suggesting that besides a decrease on BDNF levels a reduction of TrkB expression could also contribute todiminished neurotrophic support in HD. BDNF can also bind to p75 neurotrophin receptor (p75NTR) modulating TrkB signaling.Therefore, in this study we have analyzed the levels of p75NTRin several HD models, as well as in HD human brain. Our datademonstrates a p75NTR/TrkB imbalance in the striatum of two different HD mouse models,HdhQ111/111homozygous knockin miceand R6/1 mice that was also manifested in the putamen of HD patients. The imbalance between TrkB and p75NTRlevels in a HDcellular model did not affect BDNF-mediated TrkB activation of prosurvival pathways but induced activation of apoptoticcascades as demonstrated by increased JNK phosphorylation. Moreover, BDNF failed to protect mutant huntingtin striatal cellstransfected with p75NTRagainst 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 andBDNF. Altogether, our findings demonstrate that the p75NTR/TrkB imbalance induced by mutant huntingtin in striatal cellsassociated with the aberrant activity of PP1 disturbs BDNF neuroprotection likely contributing to increasing striatal vulnerabilityin HD. On the basis of this data we hypothesize that normalization of p75NTRand/or TrkB expression or their signaling willimprove BDNF neuroprotective therapies in HD

Postnatal Foxp2 regulates early psychiatric-like phenotypes and associated molecular alterations in the R6/1 transgenic mouse model of Huntington's disease

Huntington's Disease (HD) is a devastating disorder characterized by a triad of motor, psychiatric and cognitive manifestations. Psychiatric and emotional symptoms appear at early stages of the disease which are consistently described by patients and caregivers among the most disabling. Here, we show for the first time that Foxp2 is strongly associated with some psychiatric-like disturbances in the R6/1 mouse model of HD. First, 4-week-old (juvenile) R6/1 mice behavioral phenotype was characterized by an increased impulsive-like behavior and less aggressive-like behavior. In this line, we identified an early striatal downregulation of Foxp2 protein starting as soon as at postnatal day 15 that could explain such deficiencies. Interestingly, the rescue of striatal Foxp2 levels from postnatal stages completely reverted the impulsivity-phenotype and partially the social impairments concomitant with a rescue of dendritic spine pathology. A mass spectrometry study indicated that the rescue of spine loss was associated with an improvement of several altered proteins related with cytoskeleton dynamics. Finally, we reproduced and mimicked the impulsivity and social deficits in wild type mice by reducing their striatal Foxp2 expression from postnatal stages. Overall, these results imply that early postnatal reduction of Foxp2 might contribute to the appearance of some of the early psychiatric symptoms in HD

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

On the geography of activity: productivity but not temperature constrains discovery rates by ectotherm consumers

Consumer activity—the rate that individuals move through and discover items in their environment—can constrain population interactions and ecosystem services. We introduce a model that assumes consumer activity is co‐limited by the abundance and velocity of consumers, which in turn are constrained by two global drivers: net primary productivity (NPP) and environmental temperature, respectively. We test it with data from a recent study showing how arthropod activity decreases with latitude and elevation. The maximum discovery rates (discoveries per day) of these ectotherms increased linearly with NPP and accounted for the observed latitudinal gradient in activity. The mean temperature of the warmest month in contrast had no consistent effect on activity. An ecosystem's NPP, which provides carbon to build individuals and sugars to fuel them, can thus be an important constraint on the activity of its ectotherm consumers.This work was supported by funding from NSF DEB‐1556280. Article processing charges funded in part by University of Oklahoma Libraries.Ye

Deriving Telescope Mueller Matrices Using Daytime Sky Polarization Observations

Telescopes often modify the input polarization of a source so that the measured circular or linear output state of the optical signal can be signficantly different from the input. This mixing, or polarization "cross-talk", is defined by the optical system Mueller matrix. We describe here an efficient method for recovering the input polarization state of the light and the full 4 x 4 Mueller matrix of the telescope with an accuracy of a few percent without external masks or telescope hardware modification. Observations of the bright, highly polarized daytime sky using the Haleakala 3.7m AEOS telescope and a coude spectropolarimeter demonstrate the technique.Comment: Accepted for publication in PAS

High expression of prolactin receptor is associated with cell survival in cervical cancer cells

Background: The altered expression of prolactin (PRL) and its receptor (PRLR) has been implicated in breast and other types of cancer. There are few studies that have focused on the analysis of PRL/PRLR in cervical cancer where the development of neoplastic lesions is influenced by the variation of the hormonal status. The aim of this study was to evaluate the expression of PRL/PRLR and the effect of PRL treatment on cell proliferation and apoptosis in cervical cancer cell lines. Results:High expression of multiple PRLR forms and PRLvariants of 60-80 kDa were observed in cervical cancer cell lines compared with non-tumorigenic keratinocytes evaluated by Western blot, immunofluorecence and real time PCR. Treatment with PRL (200 ng/ml) increased cell proliferation in HeLa cells determined by the MTT assay at day 3 and after 1 day a protective effect against etoposide induced apoptosis in HeLa, SiHa and C-33A cervical cancer cell lines analyzed by the TUNEL assay. Conclusions: Our data suggests that PRL/PRLR signaling could act as an important survival factor for cervical cancer. The use of an effective PRL antagonist may provide a better therapeutic intervention in cervical cancer. � 2013 Lopez-Pulido et al.; licensee BioMed Central Ltd

Magnetic phase diagram of nanostructured zinc ferrite as a function of inversion degree delta

Magnetic properties of spinel zinc ferrites are strongly linked to the synthesis method and the processing route since they control the microstructure of the resulting material. In this work, ZnFe_2O_4 nanoparticles were synthesized by the mechanochemical reaction of stoichiometric ZnO and alpha-Fe2O3, and single-phase ZnFe_2O_4 was obtained after 150 h of milling. The as-milled samples, with a high inversion degree, were subjected to different thermal annealings up to 600 ºC to control the inversion degree and, consequently, the magnetic properties. The as-milled samples, with a crystallite size of 11 nm and inversion degree delta = 0.57, showed ferrimagnetic behavior even above room temperature, as shown by Rietveld refinements of the X-ray diffraction pattern and superconducting quantum interference device magnetometry. The successive thermal treatments at 300, 400, 500, and 600 degrees C decrease delta from 0.15 to 0.18, affecting the magnetic properties. A magnetic phase diagram as a function of delta can be inferred from the results: for delta 0.5, a new antiferromagnetic order appeared due to the overpopulation of nonmagnetic Zn on octahedral sites that leads to equally distributed magnetic cations in octahedral and tetrahedral sites