976 research outputs found

    LC-MS proteomics analysis of the iInsulin/IGF-1-deficient Caenorhabditis elegans daf-2(e1370) mutant reveals extensive restructuring of intermediary metabolism

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    The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity, and metabolism in Caenorhabditis elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including the expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass spectrometry (LC-MS)-based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2);daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the upregulation of many core intermediary metabolic pathways. These include glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid beta-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complexes I, II, III, and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative of spatiotemporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. This restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves and possibly also shunting metabolites through alternative energy-generating pathways to sustain longevity

    A View not to be Missed: Salient Scene Content Interferes With Cognitive Restoration

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    Attention Restoration Theory (ART) states that built scenes place greater load on attentional resources than natural scenes. This is explained in terms of "hard" and "soft" fascination of built and natural scenes. Given a lack of direct empirical evidence for this assumption we propose that perceptual saliency of scene content can function as an empirically derived indicator of fascination. Saliency levels were established by measuring speed of scene category detection using a Go/No-Go detection paradigm. Experiment 1 shows that built scenes are more salient than natural scenes. Experiment 2 replicates these findings using greyscale images, ruling out a colour-based response strategy, and additionally shows that built objects in natural scenes affect saliency to a greater extent than the reverse. Experiment 3 demonstrates that the saliency of scene content is directly linked to cognitive restoration using an established restoration paradigm. Overall, these findings demonstrate an important link between the saliency of scene content and related cognitive restoration

    Demonstration of safety of intravenous immunoglobulin in geriatric patients in a long-term, placebo-controlled study of Alzheimer's disease.

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    INTRODUCTION:We present safety results from a study of Gammagard Liquid intravenous immunoglobulin (IGIV) in patients with probable Alzheimer's disease. METHODS:This was a placebo-controlled double-blind study. Subjects were randomized to 400 mg/kg (n = 127), 200 mg/kg (n = 135) IGIV, or to 0.25% human albumin (n = 121) administered every 2 weeks ± 7 days for 18 months. RESULTS:Elevated risk ratios of IGIV versus placebo included chills (3.85) in 9.5% of IGIV-treated subjects (all doses), compared to 2.5% of placebo-treated subjects, and rash (3.08) in 15.3% of IGIV-treated subjects versus 5.0% of subjects treated with placebo. Subjects in the highest IGIV dose group had the lowest proportion of SAEs considered related to product (2 of 127 [1.6%]). Subjects treated with IGIV experienced a lower rate of respiratory and all other infections compared to placebo. DISCUSSION:IGIV-treated subjects did not experience higher rates of renal failure, lung injury, or thrombotic events than the placebo group. There were no unexpected safety findings. IGIV was well tolerated throughout 18 months of treatment in subjects aged 50-89 years

    Narrative, identity, and recovery from serious mental illness: A life history of a runner

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    In recent years, researchers have investigated the psychological effects of exercise for people with mental health problems, often by focusing on how exercise may alleviate symptoms of mental illness. In this article I take a different tack to explore the ways in which exercise contributed a sense of meaning, purpose, and identity to the life of one individual named Ben, a runner diagnosed with schizophrenia. Drawing on life history data, I conducted an analysis of narrative to explore the narrative types that underlie Ben's stories of mental illness and exercise. For Ben, serious mental illness profoundly disrupted a pre-existing athletic identity removing agency, continuity, and coherence from his life story. By returning to exercise several years later, Ben reclaimed his athletic identity and reinstated some degree of narrative agency, continuity, and coherence. While the relationships between narrative, identity, and mental health are undoubtedly complex, Ben's story suggests that exercise can contribute to recovery by being a personally meaningful activity which reinforces identity and sense of self

    Fact sheet: Using a terrestrial ecosystem survey to estimate the historical density of ponderosa pine trees in northern Arizona

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    The Terrestrial Ecosystem Survey (TES) delineates ecosystems according to their climate, geology, soils, and potential natural vegetation (U.S. Forest Service 1986). Land managers and planners can use this information to help interpret site suitability for natural regeneration, reforestation, and revegetation potential as well as site suitability for road building, range and timber, range structures (watering sources), and other land uses. However, the TES can be used for other purposes as Ganey and Benoit (2002) demonstrated in their report about identifying potential habitat for Mexican spotted owl on national forest lands. Similarly, Bell and colleagues (2009) used the TES and its specific survey units (TESU) to analyze the characteristics of the Woolsey plots in northern Arizona - plots the Forest Service established in the early 1900s to examine tree regeneration. In our study, we identified historic ponderosa pine densities on various TES mapping units and then correlated our findings with what the TESU predicted we should find
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