Neuronal activity regulates extracellular tau in vivo

Tau is primarily a cytoplasmic protein that stabilizes microtubules. However, it is also found in the extracellular space of the brain at appreciable concentrations. Although its presence there may be relevant to the intercellular spread of tau pathology, the cellular mechanisms regulating tau release into the extracellular space are not well understood. To test this in the context of neuronal networks in vivo, we used in vivo microdialysis. Increasing neuronal activity rapidly increased the steady-state levels of extracellular tau in vivo. Importantly, presynaptic glutamate release is sufficient to drive tau release. Although tau release occurred within hours in response to neuronal activity, the elimination rate of tau from the extracellular compartment and the brain is slow (half-life of ∼11 d). The in vivo results provide one mechanism underlying neuronal tau release and may link trans-synaptic spread of tau pathology with synaptic activity itself

Quasiclassical magnetotransport in a random array of antidots

We study theoretically the magnetoresistance $\rho_{xx}(B)$ of a two-dimensional electron gas scattered by a random ensemble of impenetrable discs in the presence of a long-range correlated random potential. We believe that this model describes a high-mobility semiconductor heterostructure with a random array of antidots. We show that the interplay of scattering by the two types of disorder generates new behavior of $\rho_{xx}(B)$ which is absent for only one kind of disorder. We demonstrate that even a weak long-range disorder becomes important with increasing $B$. In particular, although $\rho_{xx}(B)$ vanishes in the limit of large $B$ when only one type of disorder is present, we show that it keeps growing with increasing $B$ in the antidot array in the presence of smooth disorder. The reversal of the behavior of $\rho_{xx}(B)$ is due to a mutual destruction of the quasiclassical localization induced by a strong magnetic field: specifically, the adiabatic localization in the long-range Gaussian disorder is washed out by the scattering on hard discs, whereas the adiabatic drift and related percolation of cyclotron orbits destroys the localization in the dilute system of hard discs. For intermediate magnetic fields in a dilute antidot array, we show the existence of a strong negative magnetoresistance, which leads to a nonmonotonic dependence of $\rho_{xx}(B)$.Comment: 21 pages, 13 figure

The clinical and functional significance of c-Met in breast cancer: a review

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.CMH-Y is funded by a Cancer Research UK Clinical Research Fellowship. JLJ is funded by the Breast Cancer Campaign Tissue Bank

The state of the art in the analysis of two-dimensional gel electrophoresis images

Software-based image analysis is a crucial step in the biological interpretation of two-dimensional gel electrophoresis experiments. Recent significant advances in image processing methods combined with powerful computing hardware have enabled the routine analysis of large experiments. We cover the process starting with the imaging of 2-D gels, quantitation of spots, creation of expression profiles to statistical expression analysis followed by the presentation of results. Challenges for analysis software as well as good practices are highlighted. We emphasize image warping and related methods that are able to overcome the difficulties that are due to varying migration positions of spots between gels. Spot detection, quantitation, normalization, and the creation of expression profiles are described in detail. The recent development of consensus spot patterns and complete expression profiles enables one to take full advantage of statistical methods for expression analysis that are well established for the analysis of DNA microarray experiments. We close with an overview of visualization and presentation methods (proteome maps) and current challenges in the field

Advances in the therapy of Alzheimer's disease: Targeting amyloid beta and tau and perspectives for the future

Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD

Making the brain glow: In vivo bioluminescence imaging to study neurodegeneration

© 2012 Springer Science+Business Media New York

Regulatable transgenic mouse models of Alzheimer disease: Onset, reversibility and spreading of Tau pathology

© 2013 FEBS