Curcumin Inhibits Neuronal and Vascular Degeneration in Retina after Ischemia and Reperfusion Injury

Neuron loss, glial activation and vascular degeneration are common sequelae of ischemia-reperfusion (I/R) injury in ocular diseases. The present study was conducted to explore the ability of curcumin to inhibit retinal I/R injury, and to investigate underlying mechanisms of the drug effects.Different dosages of curcumin were administered. I/R injury was induced by elevating the intraocular pressure for 60 min followed by reperfusion. Cell bodies, brn3a stained cells and TUNEL positive apoptotic cells in the ganglion cell layer (GCL) were quantitated, and the number of degenerate capillaries was assessed. The activation of glial cells was measured by the expression level of GFAP. Signaling pathways including IKK-IκBα, JAK-STAT1/3, ERK/MAPK and the expression levels of β-tubulin III and MCP-1 were measured by western blot analysis. Pre-treatment using 0.01%-0.25% curcumin in diets significantly inhibited I/R-induced cell loss in GCL. 0.05% curcumin pre-treatment inhibited I/R-induced degeneration of retinal capillaries, TUNEL-positive apoptotic cell death in the GCL, brn3a stained cell loss, the I/R-induced up-regulation of MCP-1, IKKα, p-IκBα and p-STAT3 (Tyr), and down-regulation of β-tubulin III. This dose showed no effect on injury-induced GFAP overexpression. Moreover, 0.05% curcumin administered 2 days after the injury also showed a vaso-protective effect.Curcumin protects retinal neurons and microvessels against I/R injury. The beneficial effects of curcumin on neurovascular degeneration may occur through its inhibitory effects on injury-induced activation of NF-κB and STAT3, and on over-expression of MCP-1. Curcumin may therefore serve as a promising candidate for retinal ischemic diseases

TWEAK/Fn14 Signaling Axis Mediates Skeletal Muscle Atrophy and Metabolic Dysfunction

doi: 10.3389/fimmu.2014.00018 TWEAK/Fn14 signaling axis mediates skeletal muscle atrophy and metabolic dysfunctio

Unscented Kalman Filter for Brain-Machine Interfaces

Brain machine interfaces (BMIs) are devices that convert neural signals into commands to directly control artificial actuators, such as limb prostheses. Previous real-time methods applied to decoding behavioral commands from the activity of populations of neurons have generally relied upon linear models of neural tuning and were limited in the way they used the abundant statistical information contained in the movement profiles of motor tasks. Here, we propose an n-th order unscented Kalman filter which implements two key features: (1) use of a non-linear (quadratic) model of neural tuning which describes neural activity significantly better than commonly-used linear tuning models, and (2) augmentation of the movement state variables with a history of n-1 recent states, which improves prediction of the desired command even before incorporating neural activity information and allows the tuning model to capture relationships between neural activity and movement at multiple time offsets simultaneously. This new filter was tested in BMI experiments in which rhesus monkeys used their cortical activity, recorded through chronically implanted multielectrode arrays, to directly control computer cursors. The 10th order unscented Kalman filter outperformed the standard Kalman filter and the Wiener filter in both off-line reconstruction of movement trajectories and real-time, closed-loop BMI operation

Shortening NMR diffusion experimental times

NMR diffusion measurements have become the method of choice for measuring diffusing due to their wide applicability, speed of measurement, enormous range of accessible diffusion coefficients (from gas ~10-6 m2s-1 to large polymers ~10-15 m2s-1), and the ability to measure diffusion over a specified timescale, Δ, which greatly adds to the power of NMR diffusion measurements as it allows the ability to probe porous media [1,2]. The weakness of NMR diffusion measurements lies in their inherent insensitivity. Consequently, many experiments are in theory possible but in practice would simply consume too much spectrometer time and therefore become impractical. Even in cases where the total measurement time is not a limitation, making the measurement faster expands the horizons of diffusion measurements to study reaction kinetics [3,4], as well as simply increasing throughput

Five High-Redshift Quasars Discovered in Commissioning Imaging Data of the Sloan Digital Sky Survey

We report the discovery of five quasars with redshifts of 4.67 - 5.27 and z'-band magnitudes of 19.5-20.7 M_B ~ -27. All were originally selected as distant quasar candidates in optical/near-infrared photometry from the Sloan Digital Sky Survey (SDSS), and most were confirmed as probable high-redshift quasars by supplementing the SDSS data with J and K measurements. The quasars possess strong, broad Lyman-alpha emission lines, with the characteristic sharp cutoff on the blue side produced by Lyman-alpha forest absorption. Three quasars contain strong, broad absorption features, and one of them exhibits very strong N V emission. The amount of absorption produced by the Lyman-alpha forest increases toward higher redshift, and that in the z=5.27 object (D_A ~ 0.7) is consistent with a smooth extrapolation of the absorption seen in lower redshift quasars. The high luminosity of these objects relative to most other known objects at z >~ 5 makes them potentially valuable as probes of early quasar properties and of the intervening intergalactic medium.Comment: 13 pages in LaTex format, two postscirpt figures. Submitted to the Astronomical Journa

Genetic interactions affecting human gene expression identified by variance association mapping

Non-additive interaction between genetic variants, or epistasis, is a possible explanation for the gap between heritability of complex traits and the variation explained by identified genetic loci. Interactions give rise to genotype dependent variance, and therefore the identification of variance quantitative trait loci can be an intermediate step to discover both epistasis and gene by environment effects (GxE). Using RNA-sequence data from lymphoblastoid cell lines (LCLs) from the TwinsUK cohort, we identify a candidate set of 508 variance associated SNPs. Exploiting the twin design we show that GxE plays a role in ∼70% of these associations. Further investigation of these loci reveals 57 epistatic interactions that replicated in a smaller dataset, explaining on average 4.3% of phenotypic variance. In 24 cases, more variance is explained by the interaction than their additive contributions. Using molecular phenotypes in this way may provide a route to uncovering genetic interactions underlying more complex traits.DOI: http://dx.doi.org/10.7554/eLife.01381.001