Inflammation as a Central Mechanism in Alzheimer\u27s Disease

Alzheimer\u27s disease (AD) is a progressive neurodegenerative disorder that is characterized by cognitive decline and the presence of two core pathologies, amyloid β plaques and neurofibrillary tangles. Over the last decade, the presence of a sustained immune response in the brain has emerged as a third core pathology in AD. The sustained activation of the brain\u27s resident macrophages (microglia) and other immune cells has been demonstrated to exacerbate both amyloid and tau pathology and may serve as a link in the pathogenesis of the disorder. In the following review, we provide an overview of inflammation in AD and a detailed coverage of a number of microglia-related signaling mechanisms that have been implicated in AD. Additional information on microglia signaling and a number of cytokines in AD are also reviewed. We also review the potential connection of risk factors for AD and how they may be related to inflammatory mechanisms

Differences between neurosurgeons and orthopaedic surgeons in classifying cervical dislocation injuries and making assessment and treatment decisions: a multicenter reliability study

Journal ArticleVariability exists in the management of cervical spinal injuries. The goal of this study was to assess the effect of training specialty (orthopedic surgery vs neurosurgery) on management of cervical dislocations

Mid-frequency aperture arrays: the future of radio astronomy

Aperture array (AA) technology is at the forefront of new developments and discoveries in radio astronomy. Currently LOFAR is successfully demonstrating the capabilities of dense and sparse AA's at low frequencies. For the mid-frequencies, from 450 to 1450MHz, AA's still have to prove their scientific value with respect to the existing dish technology. Their large field-of-view and high flexibility puts them in an excellent position to do so. The Aperture Array Verification Program is dedicated to demonstrate the feasibility of AA's for science in general and SKA in particular. For the mid-frequency range this has lead to the development of EMBRACE, which has already demonstrated the enormous flexibility of AA systems by observing HI and a pulsar simultaneously. It also serves as a testbed to demonstrate the technological reliability and stability of AA's. The next step will put AA technology at a level where it can be used for cutting-edge science. In this paper we discuss the developments to move AA technology from an engineering activity to a fully science capable instrument. We present current results from EMBRACE, ongoing tests of the system, and plans for EMMA, the next step in mid-frequency AA technology.Comment: 8 pages, 7 figures, proceedings of Resolving The Sky - Radio Astronomy: Past, Present and Future (RTS2012), April 17-20, 2012, Manchester, U

Genetic and environmental influences on lamb carcass indices and muscle fiber ratios

Two concurrent trials were conducted to examine genetic and environmental influences on growth rate, carcass fatness and muscle fiber type proportions. Trial 1 compared Polypay and Coopworth x Polypay male lambs either left intact or castrated early, mid or late in growth. Trial two compared Hampshire sired lambs (females, early castrated wethers and late castrated wethers) from Suffolk x Coopworth dams and whiteface x Coopworth dams. Half the lambs in each trial were raised from weaning to the standard 52 kg slaughter weight in drylot while the other half were raised to 41 kg on pasture before finishing in drylot. Sex and delaying castration both significantly affected growth rate in Trial 1 but not in Trial 2 and had no effect on feed efficiency in either trial. Rams were leaner than wethers (P<.001) which were leaner than ewes (P<.001). No significant differences were observed between the sexes in fiber type proportions of the M. longissimus. Late castrates had less carcass fat (P<.01) than early castrates. Early castration increased the proportion of alpha red fibers in Trial 1 (P<.01) but had no effect in Trial 2. Substitution of Polypay genes with Coopworth genes did not significantly affect growth rate on either pasture or in drylot and did not alter any of the fatness traits measured. Polypay lambs had a higher proportion of beta red fibers (P<.05) than the Coopworth x Polypay lambs. No differences in fiber proportions due to genotype were detected in Trial 2. Lambs grazed on pasture and then finished in drylot had lower growth rates (P<.01). They were leaner and had a lower dressing percentage than the lambs fed in the drylot throughout, however, USDA quality grades were similar. Drylot lambs had a higher proportion of beta red fibers, the difference being 5% in Trial 2 (P<.01). Single born lambs in Trial 1 had a 6% higher proportion of alpha white fibers (P<.05) than the twin born lambs, but this difference was not seen in Trial 2. Muscle fiber proportions were not found to be related to the induced differences in growth and carcass fatness, and no evidence of differential fiber transformation was found in this experiment

Recruitment of faster motor units is associated with greater rates of fascicle strain and rapid changes in muscle force during locomotion

Animals modulate the power output needed for different locomotor tasks through changes in muscle force production and fascicle strain rate. To generate sufficient force, appropriate motor unit recruitment must occur. Given that faster motor units contract with faster strain rates and have faster activation-deactivation rates, it is therefore likely that faster motor units are recruited for more rapid movements. The goals of this study were to 1) describe changes in motor unit recruitment patterns that occur with changes in locomotor dynamics and 2) test whether motor unit recruitment can be directly related to in vivo measures of muscle force and fascicle strain and strain rate, and thus mechanical work. Myoelectric, sonomicrometric, and muscle-tendon force data were collected from the lateral and medial gastrocnemius muscles of the goat hind limb during level and incline walking and trotting, and level galloping. Myoelectric signals were analyzed using wavelet and principal component analysis in order to quantify changes to the myoelectric frequency spectra across locomotor conditions. Fascicle strain and strain rate were calculated from the sonomicrometric data, and force rate was calculated from the tendon force data. The results of this study demonstrate that, under certain locomotor conditions such as level galloping and incline walking, where EMG activity were similar but had different frequency components, faster and slower motor units are recruited in patterns that were task-specific. The study also shows that the recruitment patterns of different motor unit types are related to in vivo fascicle strain rates in addition to myoelectric intensity and force. Together, these data provide evidence that changes in motor unit recruitment have an underlying mechanical basis, at least for certain locomotor tasks.Organismic and Evolutionary Biolog

A Panel of Cytochrome P450 BM3 Variants to Produce Drug Metabolites and Diversify Lead Compounds

Herein we demonstrate that a small panel of variants of cytochrome P450 BM3 from Bacillus megaterium covers the breadth of reactivity of human P450s by producing 12 of 13 mammalian metabolites for two marketed drugs, verapamil and astemizole, and one research compound. The most active enzymes support preparation of individual metabolites for preclinical bioactivity and toxicology evaluations. Underscoring their potential utility in drug lead diversification, engineered P450 BM3 variants also produce novel metabolites by catalyzing reactions at carbon centers beyond those targeted by animal and human P450s. Production of a specific metabolite can be improved by directed evolution of the enzyme catalyst. Some variants are more active on the more hydrophobic parent drug than on its metabolites, which limits production of multiply-hydroxylated species, a preference that appears to depend on the evolutionary history of the P450 variant