Heparan sulfate proteoglycans mediate Aβ-induced oxidative stress and hypercontractility in cultured vascular smooth muscle cells

HSPG mitigates Aβ1-40-induced mitochondrial and cytosolic ROS production in VSMC under physiological oxygen concentration. To determine if differing levels oxygen impact ROS production in Aβ1-40 treated VSMC, cells were kept in 10 % oxygen (Panel A) or 1 % oxygen (conditions that are considered hypoxic; Panel B) in cell culture incubator with % 5 CO2. Primary human cerebral VSMC were pre-treated with heparin (15 U/mL), heparinase I (HpnI; 5 Sigma U/mL), or heparinase III (HpnIII; 2 Sigma U/mL) for 2 h, washed, loaded with Mitotracker Red CM-H2XRos, washed, and treated with Aβ1-40. In some cases, cells were pre-treated with heat-inactivated (HI) enzyme. Fluorescence was measured after 30 minutes. Results are representative of 3 independent experiments performed in triplicate. *p < 0.05 vs. vehicle-treated control. #p < 0.05 vs. comparison group. (JPEG 70 kb

Genetics Ignite Focus on Microglial Inflammation in Alzheimer\u27s Disease

In the past five years, a series of large-scale genetic studies have revealed novel risk factors for Alzheimer\u27s disease (AD). Analyses of these risk factors have focused attention upon the role of immune processes in AD, specifically microglial function. In this review, we discuss interpretation of genetic studies. We then focus upon six genes implicated by AD genetics that impact microglial function: TREM2, CD33, CR1, ABCA7, SHIP1, and APOE. We review the literature regarding the biological functions of these six proteins and their putative role in AD pathogenesis. We then present a model for how these factors may interact to modulate microglial function in AD

Elastic Scattering by Deterministic and Random Fractals: Self-Affinity of the Diffraction Spectrum

The diffraction spectrum of coherent waves scattered from fractal supports is calculated exactly. The fractals considered are of the class generated iteratively by successive dilations and translations, and include generalizations of the Cantor set and Sierpinski carpet as special cases. Also randomized versions of these fractals are treated. The general result is that the diffraction intensities obey a strict recursion relation, and become self-affine in the limit of large iteration number, with a self-affinity exponent related directly to the fractal dimension of the scattering object. Applications include neutron scattering, x-rays, optical diffraction, magnetic resonance imaging, electron diffraction, and He scattering, which all display the same universal scaling.Comment: 20 pages, 11 figures. Phys. Rev. E, in press. More info available at http://www.fh.huji.ac.il/~dani

The TRMM Multi-satellite Precipitation Analysis (TMPA): Quasi-Global Precipitation Estimates at Fine Scales

The TRMM Multi-satellite Precipitation Analysis (TMPA) provides a calibration-based sequential scheme for combining multiple precipitation estimates from satellites, as well as gauge analyses where feasible, at fine scales (0.25 degrees x 0.25 degrees and 3-hourly). It is available both after and in real time, based on calibration by the TRMM Combined Instrument and TRMM Microwave Imager precipitation products, respectively. Only the after-real-time product incorporates gauge data at the present. The data set covers the latitude band 50 degrees N-S for the period 1998 to the delayed present. Early validation results are as follows: The TMPA provides reasonable performance at monthly scales, although it is shown to have precipitation rate dependent low bias due to lack of sensitivity to low precipitation rates in one of the input products (based on AMSU-B). At finer scales the TMPA is successful at approximately reproducing the surface-observation-based histogram of precipitation, as well as reasonably detecting large daily events. The TMPA, however, has lower skill in correctly specifying moderate and light event amounts on short time intervals, in common with other fine-scale estimators. Examples are provided of a flood event and diurnal cycle determination

Frequency dependence of orthogonal polarisation modes in pulsars

We have carried out a study of the orthogonal polarisation mode behaviour as a function of frequency of 18 pulsars, using average pulsar data from the European Pulsar Network (EPN). Assuming that the radiation consists of two 100% polarised completely orthogonal superposed modes we separated these modes, resulting in average pulse profiles of each mode at multiple frequencies for each pulsar. Furthermore, we studied the frequency dependence of the relative intensity of these modes. We found in many pulsars that the average pulse profiles of the two modes differ in their dependence on frequency. In particular, we found that pulse components that are dominated by one mode tend to increase in intensity with increasing frequency with respect to the rest of the profile.Comment: 31 pages, 24 figures, 1 table, accepted by A&A; added references in introductio

Different Perspectives of a Factory of the Future: An Overview

Digitalfactory,andCloudManufacturingaretwoapproaches that aim at addressing the Factory of the Future, i.e., to provide digital support to manufacturing factories. They find their roots in two different geographical areas, respectively Europe and China, and therefore presents some differences as well as the same goal of building the factory of the future. In this paper, we present both the digital factory and the cloud manufacturing approaches and discuss their differences

Smokeless Tobacco Use and the Risk of Head and Neck Cancer: Pooled Analysis of US Studies in the INHANCE Consortium

Previous studies on smokeless tobacco use and head and neck cancer (HNC) have found inconsistent and often imprecise estimates, with limited control for cigarette smoking. Using pooled data from 11 US case-control studies (1981–2006) of oral, pharyngeal, and laryngeal cancers (6,772 cases and 8,375 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, we applied hierarchical logistic regression to estimate odds ratios and 95% confidence intervals for ever use, frequency of use, and duration of use of snuff and chewing tobacco separately for never and ever cigarette smokers. Ever use (versus never use) of snuff was strongly associated with HNC among never cigarette smokers (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.08, 2.70), particularly for oral cavity cancers (OR = 3.01, 95% CI: 1.63, 5.55). Although ever (versus never) tobacco chewing was weakly associated with HNC among never cigarette smokers (OR = 1.20, 95% CI: 0.81, 1.77), analyses restricted to cancers of the oral cavity showed a stronger association (OR = 1.81, 95% CI: 1.04, 3.17). Few or no associations between each type of smokeless tobacco and HNC were observed among ever cigarette smokers, possibly reflecting residual confounding by smoking. Smokeless tobacco use appears to be associated with HNC, especially oral cancers, with snuff being more strongly associated than chewing tobacco

Original Contribution Oxidative modification to LDL receptor-related protein 1 in hippocampus from subjects with Alzheimer disease: Implications for Aβ accumulation in AD brain

Alzheimer disease (AD) is a neurodegenerative disorder characterized histopathologically by the presence of senile plaques (SPs), neurofibrillary tangles, and synapse loss. The main component of SPs is amyloid-β peptide (Aβ), which has been associated with increased oxidative stress, leading to oxidative modification of proteins and consequently to neurotoxicity and neurodegeneration. Low-density lipoprotein receptor-related protein 1 (LRP1) is the primary moiety responsible for the efflux of Aβ from the brain to the blood across the blood-brain barrier. Impaired brain-to-blood transport of Aβ by LRP1 has been hypothesized to contribute to increased levels of Aβ in AD brain. The cause of LRP1 dysfunction is unknown, but we have hypothesized that Aβ oxidizes LRP1, thus damaging its own transporter. Consistent with this notion, we report in this study a significant increase in the levels of the lipid peroxidation product 4-hydroxy-2-nonenal bound to transmembrane LRP1 in AD hippocampus. In contrast, the levels of LRP1-resident 3-nitrotyrosine did not show a significant increase in AD hippocampus compared to age-matched controls. Based on this study, we propose that Aβ impairs its own efflux from the brain by oxidation of its transporter LRP1, leading to increased Aβ deposition in brain, thereby contributing to subsequent cognitive impairment in AD. © 2010 Elsevier Inc. All rights reserved. Alzheimer disease (AD) is characterized pathologically by the presence of senile plaques (SPs), neurofibrillary tangles (NFTs), and decreased synaptic density The neurovascular hypothesis of AD states that impairment of the efflux of Aβ from the brain to the blood at the blood-brain barrier (BBB) is an important mechanism underlying Aβ accumulation in the brain and contributes to subsequent cognitive impairment in AD patient