Bryostatin-1 vs. TPPB: Dose-Dependent APP Processing and PKC-α, -δ, and -ε Isoform Activation in SH-SY5Y Neuronal Cells

Activation of the α-secretase processing pathway of amyloid precursor protein (APP) is recognized as an important mechanism which diverts APP processing from production of beta-amyloid (Aβ) to non toxic sAPPα, decreasing Alzheimer’s disease (AD) plaque formation and AD-associated cognitive deficits. Two potent classes of PKC modulators can activate the α-secretase pathway, the benzo/indolactams and bryostatin/bryologues. While both modulate PKC-dependent APP processing, no direct comparisons of their relative pharmacological potencies have been accomplished which could assist in the development of AD therapies. In this study, we measured the activation of α-secretase APP processing and PKC-α, -δ, and -ε induced by the benzolactam-APP modulator TPPB and bryostatin-1 in the neuroblastoma cell line SH-SY5Y which expresses APP and α- and β-secretase processing mechanisms. Bryostatin-1 produced a more rapid, potent, and sustained activation of α-secretase APP processing than TPPB and selectively activated PKC-δ and PKC-ε. Although TPPB also activated α-secretase, its potency was approximately 10- to 100-fold lower, possibly reflecting lower PKC-δ and -ε activation. Because bryostatin-1 is a highly potent PKC-δ and -ε activator which activates α-secretase APP processing, further characterization of bryostatin-1/bryologues may help refine their use as important tools for the clinical management of AD

Surface velocity fields of active rock glaciers and ice-debris complexes in the Central Andes of Argentina

Rock glaciers and transitional ice-debris complexes predominate the Central Andean landform assemblage, yet regional studies on their state of activity and their kinematics remain sparse. Here we utilize the national glacier inventory of Argentina to quantify surface velocity fields of 244 rock glaciers and 51 ice-debris complexes, located in the Cordón del Plata range, Argentina. Applying a feature-tracking approach to repeated RapidEye satellite imagery acquired between 2010 and 2017/18, we find mean displacement rates between 0.37 and 2.61 m year−1 for 149 landforms, while for the remaining 146 features, surface movement remains below our level of detection. We compare our satellite-derived velocity fields with ground-truth data from two local field sites and find closely matching results in magnitude and spatial distribution. With average displacement of one-third of the active rock glaciers and ice-debris complexes exceeding 1 m year−1, the region hosts an exceptional number of fast-flowing periglacial landforms, compared to other mountain belts. Using a random forest model, we test the predictive power of 25 morphometric and topoclimatic candidate predictors for modelling the state of activity of rock glaciers and ice-debris complexes on two different scales. For entire landforms and individual landform segments, constructed along displacement centrelines, we can predict the state of activity with overall accuracies of 70.08% (mean AUROC = 0.785) and 74.86% (mean AUROC = 0.753), respectively. While topoclimatic parameters such as solar radiation and elevation are most important for entire landforms, geometric parameters become more important at the scale of landform segments. Despite tentative correlations between local slope and surface kinematics, our results point to factors integrating slope and distance to the source to govern local deformation. We conclude that feature tracking in optical imagery is feasible for regional studies in remote regions and provides valuable insight into the current state of the Andean cryosphere.Fil: Blöthe, Jan Henrik. Universitat Bonn; AlemaniaFil: Halla, Christian. Universitat Bonn; AlemaniaFil: Schwalbe, Ellen. Technische Universität Dresden; AlemaniaFil: Bottegal, Estefania Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Trombotto, Dario Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Schrott, Lothar. Universitat Bonn; Alemani

The effect of changes in air humidity on historic tapestries

Historic tapestries are textile artworks usually found hanging inside historic buildings. They form part of the European heritage have been exposed for centuries to diverse environmental conditions some of which have permanently damaged them. To inform better appropriate conservation practices, their physical behavior when exposed to environmental changes must be understood. The research conducted aimed to assess how the internal environment conditions in a historic building affects the tapestries’ structures and produce change in their strain. For this a series of experiments on a historic 19th century tapestry inside an environmental chamber carried out and cycles of moisture adsorption and desorption tested. Digital Image Correlation (DIC) and magnetic sensors developed by were used to test successive stages of expansion and retraction of the tapestry given different levels of relative humidity (RH) in the environment

Contemporary geomorphological activity throughout the proglacial area of an alpine catchment

Quantification of contemporary geomorphological activity is a fundamental prerequisite for predicting the effects of future earth surface process and landscape development changes. However, there is a lack of high-resolution spatial and temporal data on geomorphological activity within alpine catchments, which are especially sensitive to climate change, human impacts and which are amongst the most dynamic landscapes on Earth. This study used data from repeated laser scanning to identify and quantify the distribution of contemporary sediment sources and the intensity of geomorphological activity within the lower part of a glaciated alpine catchment; Ödenwinkelkees, central Austria. Spatially, geomorphological activity was discriminated by substrate class. Activity decreased in both areal extent and intensity with distance from the glacier, becoming progressively more restricted to the fluvially-dominated valley floor. Temporally, geomorphological activity was identified on annual, seasonal, weekly and daily timescales. Activity became more extensive with increasing study duration but more intense over shorter timescales, thereby demonstrating the importance of temporary storage of sediment within the catchment. The mean volume of material moved within the proglacial zone was 4400m.yr, which suggests a net surface lowering of 34mm.yr in this part of the catchment. We extrapolate a minimum of 4.8mm.yr net surface lowering across the whole catchment. These surface lowering values are approximately twice those calculated elsewhere from contemporary measurements of suspended sediment flux, and of rates calculated from the geological record, perhaps because we measure total geomorphological activity within the catchment rather than overall efflux of material. Repeated geomorphological surveying therefore appears to mitigate the problems of hydrological studies underestimating sediment fluxes on decadal-annual time-scales. Further development of the approach outlined in this study will enable the quantification of geomorphological activity, alpine terrain stability and persistence of landforms

Pathway to the PiezoElectronic Transduction Logic Device

The information age challenges computer technology to process an exponentially increasing computational load on a limited energy budget - a requirement that demands an exponential reduction in energy per operation. In digital logic circuits, the switching energy of present FET devices is intimately connected with the switching voltage, and can no longer be lowered sufficiently, limiting the ability of current technology to address the challenge. Quantum computing offers a leap forward in capability, but a clear advantage requires algorithms presently developed for only a small set of applications. Therefore, a new, general purpose, classical technology based on a different paradigm is needed to meet the ever increasing demand for data processing.Comment: in Nano Letters (2015

Trends in Metal Oxide Stability for Nanorods, Nanotubes, and Surfaces

The formation energies of nanostructures play an important role in determining their properties, including the catalytic activity. For the case of 15 different rutile and 8 different perovskite metal oxides, we find that the density functional theory (DFT) calculated formation energies of (2,2) nanorods, (3,3) nanotubes, and the (110) and (100) surfaces may be described semi-quantitatively by the fraction of metal--oxygen bonds broken and the bonding band centers in the bulk metal oxide

Apoptosis of the fibrocytes type 1 in the spiral ligament and blood labyrinth barrier disturbance cause hearing impairment in murine cerebral malaria

<p>Abstract</p> <p>Background</p> <p>Experimental murine malaria has been shown to result in significant hearing impairment. Microscopic evaluation of the temporal bones of these animals has revealed regular morphology of the cochlea duct. Furthermore, the known vascular pathologic changes being associated with malaria could not be found. Immunohistochemistry for ICAM1 showed a strong marking in the <it>stria vascularis</it>, indicating a disturbance of the endocochlear potential. The aim of this study was to evaluate the role of apoptosis and the disturbance of the blood labyrinth barrier in the murine malaria associated hearing impairment.</p> <p>Methods</p> <p>The temporal bones of seven mice with cerebral malaria-four with hearing impairment, three without hearing impairment-were evaluated with immunohistochemistry for cleaved caspase 3 to detect apoptosis and connexin 26, a gap junction protein being a cornerstone in the endocochlear potassium recirculation. Furthermore five animals with cerebral malaria were treated with Evans blue prior to sacrification to detect disturbances of the blood labyrinth barrier.</p> <p>Results</p> <p>Cleaved caspase 3 could clearly be detected by immunohistochemistry in the fibrocytes of the spiral ligament, more intensively in animals with hearing impairment, less intensively in those without. Apoptosis signal was equally distributed in the spiral ligament as was the connexin 26 gap junction protein. The Evans blue testing revealed a strong signal in the malaria animals and no signal in the healthy control animals.</p> <p>Conclusion</p> <p>Malfunction of the fibrocytes type 1 in the spiral ligament and disruption of the blood labyrinth barrier, resulting in a breakdown of the endocochlear potential, are major causes for hearing impairment in murine cerebral malaria.</p

Social Influence in Televised Election Debates: A Potential Distortion of Democracy

A recent innovation in televised election debates is a continuous response measure (commonly referred to as the “worm”) that allows viewers to track the response of a sample of undecided voters in real-time. A potential danger of presenting such data is that it may prevent people from making independent evaluations. We report an experiment with 150 participants in which we manipulated the worm and superimposed it on a live broadcast of a UK election debate. The majority of viewers were unaware that the worm had been manipulated, and yet we were able to influence their perception of who won the debate, their choice of preferred prime minister, and their voting intentions. We argue that there is an urgent need to reconsider the simultaneous broadcast of average response data with televised election debates