41 research outputs found
COX-2 in the neurodegenerative process of Parkinson's disease
No full textThe author thanks Mrs. Birgit Teismann for her help in the preparation of this manuscript. The author wishes also to acknowledge the support of the Wellcome Trust (WT080782MF) and the NHS Endowment fund (06-09). The author declares that he has no conflict of interest.Peer reviewe
MPP+-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress
No full textPeer reviewe
An Ideological City: Koolhaas’ Exodus in the Second Ecumene
No full textIn 1968 the Apollo 8 spacecraft became the first manned vehicle to orbit the moon. This mission is perhaps most famous however, for a photograph called Earthrise, taken by astronaut William Anders. Deemed by Life Books as ‘the most influential environmental photograph ever taken (Rowel, 2003, p. 172),’ it is purportedly the first photograph of our globe in-the-round. Earthrise had been preceded, however, by a 1966 black-and-white image taken by the Lunar Orbiter 1 robotic probe. Marking a seminal shift into an era signified by universal globalization, the world’s first view of Earth appropriately originated from beyond its surface. Six years later in 1972 when Rem Koolhaas created his theoretical project, 'Exodus, or the Voluntary Prisoners of Architecture,' he created an architecture against geo-economic forces of globalization. Critical to Exodus is an opposing spatial impenetrability designed to keep people in, while keeping goods, capital, and politics out. Both architecture and city, Exodus ideologically resists a newly emergent globalized world, manifest in an interconnected world-city that Greek architect Constantinos Doxiadis prefigured as 'Ecumenopolis.' Using Peter Sloterdijk's spatial analysis of globalization, I will place Exodus within this economic and historical context – a counter-cultural space at odds with global architecture and cities. As a discordant proposition, however, Koolhaas provides a place in which humans enter into an ontological space: Sloterdijk’s Sphären (Spheres).</jats:p
An Emerging International: The Imperial Gaze of the Monster Globe in 1851
No full text© 2016 The Society of Architectural Historians, Australia and New Zealand. One month after the opening of the Great Exhibition in London in 1851, one of the most compelling purpose-built panoramas was erected by cartographer James Wyld in Leicester Square. The largest model of the earth ever constructed, the Monster Globe is a gigantic hollow sphere depicting land formations in colour relief on its surface: a georama. The globe is inverted, however, so that the exterior surface of the earth is conveyed on the interior surface of the hollow sphere. Transcending traditional cartographic means, the Monster Globe represented emerging spatial conceptions, evident in the all-seeing allegorical gaze of the map. James Wyld’s ambitious scheme to respatialise human perception originates in an equally ambitious Great Exhibition of 1851. Wyld’s Monster Globe, however, has largely been forgotten. Relatively unknown and understudied, this paper will show that its importance lies as a symptom of an emerging imperial construct. Is it possible, however, the Monster Globe is both symptomatic of modern imperialism while also emblematic of a not-yet fully realised global space? Beyond mere historical document, this paper contends that the cartographic space of the Monster Globe stems from and prefigures specific historical conjunctures of imperial capitalism and global power
Displacement & Domesticity: Working Paper Series
No full textThe WORKING PAPER SERIES gathers results from the EAHN 2019 Thematic Conference: DISPLACEMENT & DOMESTICITY SINCE 1945: REFUGEES, MIGRANTS AND EXPATS MAKING HOMES.
The papers presented draw together different responses regarding the question of displacement and domesticity in various circumstances (e.g., forced, economic, etc.) and in relation to past, present as well as future notions of SPACE, PLACE and ARCHITECTURE. The table of contents responds to the programme of the conference (although not all presenters submitted their full paper), which was designed by the organisers to highlight common and significant themes in the papers. In addition to displacement and domesticity, these themes attempt to untangle notions of HOME, HOUSING, the CITY, GENDER and SHELTER.
Therefore, this book of working papers introduces the theme of DISPLACEMENT and DOMESTICITY as a significant one of interdisciplinary investigation for our time. It looks to continue the discussion further – to to provoke and to challenge new questions and perspectives, reconfiguring the scholarly approach to these ideas.
REFUGEES, MIGRANTS AND EXPATS MAKING HOMES conference was patronised by the EAHN in collaboration with KU Leuven Department of Architecture, the Royal Flemish Academy of Belgium and FWO.status: Published onlin
Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression
No full text\ua9 2018 The Author(s). Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype
Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
No full text\ua9 2019, The Author(s).Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk
Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder
No full textFunding: Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL), Reference 104036/Z/14/Z). The Psychiatric Genomics Consortium has received major funding from the US National Institute of Mental Health and the US National Institute of Drug Abuse (U01 MH109528 and U01 MH1095320).The 1st author AAS is funded by University of Edinburgh (www.ed.ac.uk) and Medical Research Council for his PhD study at the University of Edinburgh Institute of Genetics and Molecular Medicine (www.ed.ac.uk/igmm). MA is supported by the Wellcome Trust Strategic Award STRADL (Reference 104036/Z/14/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe
Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder
No full text© 2018 Arnau-Soler et al. This is an open access article distributed underthe terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48×10 -7 ; Bonferroni-corrected significance threshold p < 2.79×10 -6 ). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity
