The role of tissue transglutaminase in 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in differentiated human SH-SY5Y neuroblastoma cells

Tissue transglutaminase (TG2) can induce post-translational modification of proteins, resulting in protein cross-linking or incorporation of polyamines into substrates, and can also function as a signal transducing G protein. The role of TG2 in the formation of insoluble cross-links has led to its implication in some neurodegenerative conditions. Exposure of pre-differentiated SH-SY5Y cells to the Parkinsonian neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) resulted in significant dose-dependent reductions in TG2 protein levels, measured by probing Western blots with a TG2-specific antibody. Transglutaminase (TG) transamidating activity, on the other hand, monitored by incorporation of a polyamine pseudo-substrate into cellular proteins, was increased. Inhibitors of TG (putrescine) and TG2 (R283) exacerbated MPP+ toxicity, suggesting that activation of TG2 may promote a survival response in this toxicity paradigm

Love thy neighbour: group properties of gaping behaviour in mussel aggregations

By associating closely with others to form a group, an animal can benefit from a number of advantages including reduced risk of predation, amelioration of environmental conditions, and increased reproductive success, but at the price of reduced resources. Although made up of individual members, an aggregation often displays novel effects that do not manifest at the level of the individual organism. Here we show that very simple behaviour in intertidal mussels shows new effects in dense aggregations but not in isolated individuals. Perna perna and Mytilus galloprovincialis are gaping (periodic valve movement during emersion) and non-gaping mussels respectively. P. perna gaping behaviour had no effect on body temperatures of isolated individuals, while it led to increased humidity and decreased temperatures in dense groups (beds). Gaping resulted in cooler body temperatures for P. perna than M. galloprovincialis when in aggregations, while solitary individuals exhibited the highest temperatures. Gradients of increasing body temperature were detected from the center to edges of beds, but M. galloprovincialis at the edge had the same temperature as isolated individuals. Furthermore, a field study showed that during periods of severe heat stress, mortality rates of mussels within beds of the gaping P. perna were lower than those of isolated individuals or within beds of M. galloprovincialis, highlighting the determinant role of gaping on fitness and group functioning. We demonstrate that new effects of very simple individual behaviour lead to amelioration of abiotic conditions at the aggregation level and that these effects increase mussel resistance to thermal stress

Willingness to adhere to current UK low-risk alcohol guidelines to potentially reduce dementia risk: A national survey of people aged 50 and over

BACKGROUND: People over 50 are increasing their alcohol intake, potentially increasing their risk of dementia. OBJECTIVE: This study investigates whether people would be willing to adhere to current United Kingdom (UK, "low-risk") alcohol guidelines to reduce dementia risk. METHODS: A national cross-sectional online survey recruited a non-probabilistic sample of 3,948 individuals aged 50 and over without dementia in the UK. Self-reported willingness to comply with low-risk guidelines was predicted using logistic regression. Other relevant self-reported variables included physical health, lifestyle, and current alcohol intake. RESULTS: Majority of the sample (90%, n = 3,527) reported drinking alcohol at least once a month with 23% (n = 795) exceeding the low-risk guidelines (> 14 units per week). A larger proportion of men, those who were overweight, and people without a partner reported drinking above the recommended level. Most people who consumed alcohol (n = 2,934; 74.3%) appeared willing to adhere to low-risk guidelines if they were told that their risk of having dementia could be reduced. Increased willingness was found in women (OR 1.81; CI 1.47-2.23), in people who had at least one child (OR 1.36; CI 1.09-1.70), and those who slept well (OR 1.45; CI 1.06-2.00). People who were obese (OR 0.72; CI 0.54-0.95), those who drank alcohol above limits (OR 0.13; CI 0.11-0.16), and those who were smokers (OR 0.56; CI 0.36-0.88) were less willing to adhere to current guidelines. CONCLUSION: Men and people with more lifestyle risk factors for common chronic diseases (e.g., smoking, obesity, and excess alcohol consumption) are less willing to adhere to current alcohol low-risk guidelines to reduce dementia risk

A VSA search for the extended Sunyaev-Zel'dovich Effect in the Corona Borealis Supercluster

We present interferometric imaging at 33 GHz of the Corona Borealis supercluster, using the extended configuration of the Very Small Array. A total area of 24 deg^2 has been imaged, with an angular resolution of 11 arcmin and a sensitivity of 12 mJy/beam. The aim of these observations is to search for Sunyaev-Zel'dovich (SZ) detections from known clusters of galaxies in this supercluster and for a possible extended SZ decrement due to diffuse warm/hot gas in the intercluster medium. We measure negative flux values in the positions of the ten richest clusters in the region. Collectively, this implies a 3.0-sigma detection of the SZ effect. In the clusters A2061 and A2065 we find decrements of approximately 2-sigma. Our main result is the detection of two strong and resolved negative features at -70+-12 mJy/beam (-157+-27 microK) and -103+-10 mJy/beam (-230+-23 microK), respectively, located in a region with no known clusters, near the centre of the supercluster. We discuss their possible origins in terms of primordial CMB anisotropies and/or SZ signals related to either unknown clusters or to a diffuse extended warm/hot gas distribution. Our analyses have revealed that a primordial CMB fluctuation is a plausible explanation for the weaker feature (probability of 37.82%). For the stronger one, neither primordial CMB (probability of 0.33%) nor SZ can account alone for its size and total intensity. The most reasonable explanation, then, is a combination of both primordial CMB and SZ signal. Finally, we explore what characteristics would be required for a filamentary structure consisting of warm/hot diffuse gas in order to produce a significant contribution to such a spot taking into account the constraints set by X-ray data.Comment: 16 pages, 10 figures. Accepted in MNRA

Characterisation of uranium-pyrite associations within organic-rich Eocene sediments using EM, XFM-µXANES and µXRD

Sediments that are rich in organic matter (OM) can trap and accumulate metals, including uranium (U), and provide favourable conditions for the formation of minerals such as pyrite. In OM-sediments, pyrite may play an important role in sorption and reduction of U and other metals that are sensitive to redox change. Mulga Rock, located in Western Australia, is an Eocene polymetallic deposit hosting economic uranium within its OM-rich sediments. Our previous work on the Mulga Rock deposits showed that OM may host U(VI) for long periods and suggested that reduction to U(IV) may occur through different pathways. Framboidal-like pyrite, embedded in lignite, displaying U(IV)-rich rims, > 100 µm, were investigated using synchrotron-X-ray fluorescence microscopy-micro-X-ray absorption near edge structure (XFM-µXANES), laboratory micro-X-ray diffraction (µXRD) and electron microscopy. Micro-XRD analyses indicated that the U(IV) phase was mostly coffinite [USiO4] mixed with uraninite [UO2]. Analyses of transects across U-pyrite rims using XFM and XFM-µXANES revealed higher concentrations of U(IV) near the pyrite, and proportionally more U(VI) away from the edge of the pyrite. We infer that within OM environments, pyrite has a local influence on the oxidation state of U, which may be influential when considering U mobility

Very Small Array observations of the Sunyaev-Zel'dovich effect in nearby galaxy clusters

We present VSA observations (~34GHz) on scales ~20 arcmin towards a complete, X-ray-flux-limited sample of seven clusters at redshift z<0.1. Four have significant SZ detections in the presence of CMB primordial anisotropy. We use a bayesian MCMC method for inference from the VSA data, with X-ray priors on cluster positions and temperatures, and radio priors on sources. We make assumptions of beta-model gas distributions and of hydrostatic equilibrium, to evaluate probability densities for the gas mass and total mass out to r_200. Our combined estimate of the gas fraction is 0.08^{+0.06}_{-0.04}h^{-1} The random errors are poor (note that the errors are higher than would have been obtained with the usual chi-squared method) but the control of bias is good. We have described the MCMC analysis method specifically in terms of SZ but hope the description will be of more general use. We find that the effects of primordial CMB contamination tend to be similar in the estimates of both the gas mass and total mass over our narrow range of angular scales, so that there is little effect of primordials on the gas fraction determination. Using our total mass estimates we find a normalisation of the mass-temperature relation based on the profiles from the VSA cluster pressure maps that is in good agreement with recent M-T determinations from X-ray cluster measurements.Comment: Replaces earlier version. 16 pages, 5 figures, LaTeX. Minor revisions to content, accepted by MNRAS for publicatio

Searching for non-Gaussianity in the VSA data

We have tested Very Small Array (VSA) observations of three regions of sky for the presence of non-Gaussianity, using high-order cumulants, Minkowski functionals, a wavelet-based test and a Bayesian joint power spectrum/non-Gaussianity analysis. We find the data from two regions to be consistent with Gaussianity. In the third region, we obtain a 96.7% detection of non-Gaussianity using the wavelet test. We perform simulations to characterise the tests, and conclude that this is consistent with expected residual point source contamination. There is therefore no evidence that this detection is of cosmological origin. Our simulations show that the tests would be sensitive to any residual point sources above the data's source subtraction level of 20 mJy. The tests are also sensitive to cosmic string networks at an rms fluctuation level of $105 \mu K$ (i.e. equivalent to the best-fit observed value). They are not sensitive to string-induced fluctuations if an equal rms of Gaussian CDM fluctuations is added, thereby reducing the fluctuations due to the strings network to $74 \mu K$ rms . We especially highlight the usefulness of non-Gaussianity testing in eliminating systematic effects from our data.Comment: Minor corrections; accepted for publication to MNRA

Issues of collaboration, representation, meaning and emotions: Utilising participant-led visual diaries to capture the everyday lives of people in mid to later life

In recent years there has been an increasing use of visual methods in ageing research. There are, however, limited reflections and critical explorations of the implications of using visual methods in research with people in mid to later life. This paper examines key methodological complexities when researching the daily lives of people as they grow older and the possibilities and limitations of using participant-generated visual diaries. The paper will draw on our experiences of an empirical study, which included a sample of 62 women and men aged 50 years and over with different daily routines. Participant-led photography was drawn upon as a means to create visual diaries, followed by in-depth, photo-elicitation interviews. The paper will critically reflect on the use of visual methods for researching the daily lives of people in mid to later life, as well as suggesting some wider tensions within visual methods that warrant attention. First, we explore the extent to which photography facilitates a ‘collaborative’ research process; second, complexities around capturing the ‘everydayness’ of daily routines are explored; third, the representation and presentation of ‘self’ by participants within their images and interview narratives is examined; and, finally, we highlight particular emotional considerations in visualising daily life

Between a rock and a hard place? Navigating domestic and international expectations on German foreign policy

This article takes stock of German foreign policy during Angela Merkel's third term in office (2013–17). It argues that the longer-term significance of Germany's foreign policy during this period is twofold. First, the Merkel government was confronted with multiple European and international crises which worked as a magnifying glass for the growing international expectations on Germany to become more actively engaged on the international stage. Second, the tenure of the Grand Coalition saw a significant shift in the German domestic foreign policy discourse that was marked by a concerted effort of leading decision-makers to make the case for Germany to accept greater international responsibilities. This emerging consensus among foreign policy elites expresses a changed self-conception of German foreign policy which, however, continues to be viewed with scepticism in the broader public. Informed by such a broad two-level perspective that focuses on the interplay between international and domestic expectations on German foreign policy, the article explores the record of the Grand Coalition in the main international crises it had to engage with. It suggests that the Merkel government was better able to live up to its own aspirations in two-level contexts which left it with greater domestic room for manoeuvre