Selenium, selenoproteins and neurodegenerative diseases

© The Royal Society of Chemistry 2015. It is unsurprising that our understanding of the role of selenium in neurological function is somewhat immature, considering its relatively recent discovery as an essential element to human health. Selenocysteine, the 21st amino acid, is the defining feature of the 25 selenoprotein-encoding genes so far discovered within the human genome. The low abundance of these proteins in the brain belies the integral role they play in normal neurological function, from well-characterised antioxidant activity in the periphery to poorly understood mechanisms that modulate mitochondrial function and response to brain pathology. Selenium has been identified as playing a role in several neurodegenerative disorders, including Alzheimer's and Parkinson's disease, though its function as a 'cause or effect' of disease process remains unclear. This review discusses selenium metabolism in detail, specifically with regard to the role it plays within the central nervous system, and examines the most current literature investigating how selenium may be involved in chronic diseases of the central nervous system

Glutathione peroxidase 4: A new player in neurodegeneration?

© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Glutathione peroxidase 4 (GPx4) is an antioxidant enzyme reported as an inhibitor of ferroptosis, a recently discovered non-apoptotic form of cell death. This pathway was initially described in cancer cells and has since been identified in hippocampal and renal cells. In this Perspective, we propose that inhibition of ferroptosis by GPx4 provides protective mechanisms against neurodegeneration. In addition, we suggest that selenium deficiency enhances susceptibility to ferroptotic processes, as well as other programmed cell death pathways due to a reduction in GPx4 activity. We review recent studies of GPx4 with an emphasis on neuronal protection, and discuss the relevance of selenium levels on its enzymatic activity

Room reflections and constancy in speech-like sounds: within-band effects

The experiment asks whether constancy in hearing precedes or follows grouping. Listeners heard speech-like sounds comprising 8 auditory-filter shaped noise-bands that had temporal envelopes corresponding to those arising in these filters when a speech message is played. The „context‟ words in the message were “next you‟ll get _to click on”, into which a “sir” or “stir” test word was inserted. These test words were from an 11-step continuum that was formed by amplitude modulation. Listeners identified the test words appropriately and quite consistently, even though they had the „robotic‟ quality typical of this type of 8-band speech. The speech-like effects of these sounds appears to be a consequence of auditory grouping. Constancy was assessed by comparing the influence of room reflections on the test word across conditions where the context had either the same level of reflections, or where it had a much lower level. Constancy effects were obtained with these 8-band sounds, but only in „matched‟ conditions, where the room reflections were in the same bands in both the context and the test word. This was not the case in a comparison „mismatched‟ condition, and here, no constancy effects were found. It would appear that this type of constancy in hearing precedes the across-channel grouping whose effects are so apparent in these sounds. This result is discussed in terms of the ubiquity of grouping across different levels of representation

Testing the efficacy of a thermal camera as a search tool for locating wild bumble bee nests

This is the final version. Available from the publisher via the DOI in this record.Published by Informa UK Limited, trading as Taylor & Francis Group. Research into how bumble bee colonies respond to the stressors affecting their populations are currently studied in the laboratory using commercially reared Bombus terrestris colonies. Understanding how these stressors affect wild bumble bee colonies in the field would be a crucial step forward for the conservation of bumble bee species. Currently, visual cues are used to locate bumble bee nests, using human searchers looking for the worker nest traffic, but the limitations of this method mean that low numbers of nests are found and so a new method that looks to tackle these limitations is needed. Thermal cameras have been considered as a potential nest searching tool because they reduce the visual complexity of the environment by displaying a homogenized thermal landscape to the searcher. In this study, we compare the use of a thermal camera to human searches using two trials: (i) using inexperienced volunteers to search along the transect for a known bumble bee nest and (ii) using an experienced individual to search across a number of novel locations. We found thermal cameras are not a better nest detection technique than human searches, having low success rates across both trials. We discuss the limitations of thermal cameras as a technique and propose how the technology could be improved for future studies.Natural Environment Research Council (NERC

Pathwise Accuracy and Ergodicity of Metropolized Integrators for SDEs

Metropolized integrators for ergodic stochastic differential equations (SDE) are proposed which (i) are ergodic with respect to the (known) equilibrium distribution of the SDE and (ii) approximate pathwise the solutions of the SDE on finite time intervals. Both these properties are demonstrated in the paper and precise strong error estimates are obtained. It is also shown that the Metropolized integrator retains these properties even in situations where the drift in the SDE is nonglobally Lipschitz, and vanilla explicit integrators for SDEs typically become unstable and fail to be ergodic.Comment: 46 pages, 5 figure

Glacial landscape evolution in the Uummannaq region, West Greenland

The Uummannaq region is a mosaic of glacial landsystems, consistent with hypothesised landscape distribution resulting from variations in subglacial thermal regime. The region is dominated by selective linear erosion which has spatially and altitudinally partitioned the landscape. Low altitude areas are dominated by glacial scour, with higher elevations are dominated by plateaux or mountain valley and cirque glaciers. The appearance and nature of each landscape type varies locally with altitude and latitude, as a function of bedrock geology and average glacial conditions. Selective linear erosion has been a primary control on landscape distribution throughout Uummannaq, leading to plateau formation and the growth of a coalescent fjord system in the Uummannaq region. This has allowed the development of the Uummannaq ice stream’s (UIS) onset zone during glacial periods. Fjord development has been enhanced by a down-stream change in geology to less-resistant lithologies, increasing erosional efficiency and allowing a single glacial channel to develop, encouraging glacier convergence and the initiation of ice streaming. The landscape has been affected by several periods of regional uplift from 33 Ma to present, and has been subject to subsequent fluvial and glacial erosion. Uplift has removed surfaces from the impact of widespread warm-based glaciation, leaving them as relict landsurfaces. The result of this is a regional altitude-dependant continuum of glacial modification, with extreme differences in erosion between high and low elevation surfaces. This study indicates that processes of long-term uplift, glacial erosion/protection, and spatial variability in erosion intensity have produced a highly partitioned landscape

Subcellular compartmentalisation of copper, iron, manganese, and zinc in the Parkinson's disease brain

© 2017 The Royal Society of Chemistry. Elevated iron and decreased copper levels are cardinal features of the degenerating substantia nigra pars compacta in the Parkinson's disease brain. Both of these redox-active metals, and fellow transition metals manganese and zinc, are found at high concentrations within the midbrain and participate in a range of unique biological reactions. We examined the total metal content and cellular compartmentalisation of manganese, iron, copper and zinc in the degenerating substantia nigra, disease-affected but non-degenerating fusiform gyrus, and unaffected occipital cortex in the post mortem Parkinson's disease brain compared with age-matched controls. An expected increase in iron and a decrease in copper concentration was isolated to the soluble cellular fraction, encompassing both interstitial and cytosolic metals and metal-binding proteins, rather than the membrane-associated or insoluble fractions. Manganese and zinc levels did not differ between experimental groups. Altered Fe and Cu levels were unrelated to Braak pathological staging in our cases of late-stage (Braak stage V and VI) disease. The data supports our hypothesis that regional alterations in Fe and Cu, and in proteins that utilise these metals, contribute to the regional selectively of neuronal vulnerability in this disorder

Decreased copper in alzheimer's disease brain is predominantly in the soluble extractable fraction

Alzheimer's disease (AD) is the leading cause of dementia and represents a significant burden on the global economy and society. The role of transition metals, in particular copper (Cu), in AD has become of significant interest due to the dyshomeostasis of these essential elements, which can impart profound effects on cell viability and neuronal function. We tested the hypothesis that there is a systemic perturbation in Cu compartmentalization in AD, within the brain as well as in the periphery, specifically within erythrocytes. Our results showed that the previously reported decrease in Cu within the human frontal cortex was confined to the soluble (P<0.05) and total homogenate (P<0.05) fractions. No differences were observed in Cu concentration in erythrocytes. Our data indicate that there is a brain specific alteration in Cu levels in AD localized to the soluble extracted material, which is not reflected in erythrocytes. Further studies using metalloproteomics approaches will be able to elucidate the metabolic mechanism(s) that results in the decreased brain Cu levels during the progression of AD. © 2013 Alan Rembach et al