22,675 research outputs found

    Building body identities - exploring the world of female bodybuilders

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    This thesis explores how female bodybuilders seek to develop and maintain a viable sense of self despite being stigmatized by the gendered foundations of what Erving Goffman (1983) refers to as the 'interaction order'; the unavoidable presentational context in which identities are forged during the course of social life. Placed in the context of an overview of the historical treatment of women's bodies, and a concern with the development of bodybuilding as a specific form of body modification, the research draws upon a unique two year ethnographic study based in the South of England, complemented by interviews with twenty-six female bodybuilders, all of whom live in the U.K. By mapping these extraordinary women's lives, the research illuminates the pivotal spaces and essential lived experiences that make up the female bodybuilder. Whilst the women appear to be embarking on an 'empowering' radical body project for themselves, the consequences of their activity remains culturally ambivalent. This research exposes the 'Janus-faced' nature of female bodybuilding, exploring the ways in which the women negotiate, accommodate and resist pressures to engage in more orthodox and feminine activities and appearances

    The Professional Identity of Doctors who Provide Abortions: A Sociological Investigation

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    Abortion is a medicalised problem in England and Wales, where the law places doctors at the centre of legal provision and puts doctors in control of who has an abortion. However, the sex-selection abortion scandal of 2012 presented a very real threat to 'abortion doctors', when the medical profession's values and practices were questioned in the media, society and by Members of Parliament. Doctors found themselves at the centre of a series of claims that stated doctors were acting both illegally and unethically, driven by profit rather than patient needs. Yet, the perspectives of those doctors who provide abortions has been under-researched; this thesis aims to fill that gap by examining the beliefs and values of this group of doctors. Early chapters highlight the ambiguous position of the abortion provider in Britain, where doctors are seen as a collective group of professionals motivated by medical dominance and medical autonomy. They outline how this position is then questioned and contested, with doctors being presented as unethical. By studying abortion at the macro-, meso- and micro-levels, this thesis seeks to better understand the values of the 'abortion doctor', and how these levels shape the work and experiences of abortion providers in England and Wales. This thesis thus addresses the question: 'What do abortion doctors' accounts of their professional work suggest about the contemporary dynamics of the medicalisation of abortion in Britain?'. It investigates the research question using a qualitative methodological approach: face-to-face and telephone interviews were conducted with 47 doctors who provide abortions in England and Wales. The findings from this empirical study show how doctors' values are linked to how they view the 'normalisation of abortion'. At the macro-level doctors, openly resisted the medicalisation of abortion through the position ascribed to them by the legal framework, yet at the meso-level doctors construct an identity where normalising abortion is based on further medicalising services. Finally, at the micro-level, the ambiguous position of the abortion provider is further identified in terms of being both a proud provider and a stigmatised individual. This thesis shows that while the existing medicalisation literature has some utility, it has limited explanatory power when investigating the problem of abortion. The thesis thus provides some innovative insights into the relevance and value of medicalisation through a comprehensive study on doctors' values, beliefs and practices

    RNA pull-down-confocal nanoscanning (RP-CONA), a novel method for studying RNA/protein interactions in cell extracts that detected potential drugs for Parkinson’s disease targeting RNA/HuR complexes

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    MicroRNAs (miRNAs, miRs) are a class of small non-coding RNAs that regulate gene expression through specific base-pair targeting. The functional mature miRNAs usually undergo a two-step cleavage from primary miRNAs (pri-miRs), then precursor miRNAs (pre-miRs). The biogenesis of miRNAs is tightly controlled by different RNA-binding proteins (RBPs). The dysregulation of miRNAs is closely related to a plethora of diseases. Targeting miRNA biogenesis is becoming a promising therapeutic strategy. HuR and MSI2 are both RBPs. MiR-7 is post-transcriptionally inhibited by the HuR/MSI2 complex, through a direct interaction between HuR and the conserved terminal loop (CTL) of pri-miR-7-1. Small molecules dissociating pri-miR-7/HuR interaction may induce miR-7 production. Importantly, the miR-7 levels are negatively correlated with Parkinson’s disease (PD). PD is a common, incurable neurodegenerative disease causing serious motor deficits. A hallmark of PD is the presence of Lewy bodies in the human brain, which are inclusion bodies mainly composed of an aberrantly aggregated protein named α-synuclein (α-syn). Decreasing α-syn levels or preventing α-syn aggregation are under investigation as PD treatments. Notably, α-syn is negatively regulated by several miRNAs, including miR-7, miR-153, miR-133b and others. One hypothesis is that elevating these miRNA levels can inhibit α-syn expression and ameliorate PD pathologies. In this project, we identified miR-7 as the most effective α-syn inhibitor, among the miRNAs that are downregulated in PD, and with α-syn targeting potentials. We also observed potential post-transcriptional inhibition on miR-153 biogenesis in neuroblastoma, which may help to uncover novel therapeutic targets towards PD. To identify miR-7 inducers that benefit PD treatment by repressing α-syn expression, we developed a novel technique RNA Pull-down Confocal Nanoscaning (RP-CONA) to monitor the binding events between pri-miR-7 and HuR. By attaching FITC-pri-miR-7-1-CTL-biotin to streptavidin-coated agarose beads and incubating them in human cultured cell lysates containing overexpressed mCherry-HuR, the bound RNA and protein can be visualised as quantifiable fluorescent rings in corresponding channels in a confocal high-content image system. A pri-miR-7/HuR inhibitor can decrease the relative mCherry/FITC intensity ratio in RP-CONA. With this technique, we performed several small-scale screenings and identified that a bioflavonoid, quercetin can largely dissociate the pri-miR-7/HuR interaction. Further studies proved that quercetin was an effective miR-7 inducer as well as α-syn inhibitor in HeLa cells. To understand the mechanism of quercetin mediated α-syn inhibition, we tested the effects of quercetin treatment with miR-7-1 and HuR knockout HeLa cells. We found that HuR was essential in this pathway, while miR-7 hardly contributed to the α-syn inhibition. HuR can directly bind an AU-rich element (ARE) at the 3’ untranslated region (3’-UTR) of α-syn mRNA and promote translation. We believe quercetin mainly disrupts the ARE/HuR interaction and disables the HuR-induced α-syn expression. In conclusion, we developed and optimised RP-CONA, an on-bead, lysate-based technique detecting RNA/protein interactions, as well as identifying RNA/protein modulators. With RP-CONA, we found quercetin inducing miR-7 biogenesis, and inhibiting α-syn expression. With these beneficial effects, quercetin has great potential to be applied in the clinic of PD treatment. Finally, RP-CONA can be used in many other RNA/protein interactions studies

    A proteomic survival predictor for COVID-19 patients in intensive care

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    © 2022 Demichev et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. https://creativecommons.org/licenses/by/4.0/Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also needed to monitor treatment, including experimental therapies in clinical trials. Comprehensively capturing human physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index, and APACHE II score showed limited performance in predicting the COVID-19 outcome. Instead, the quantification of 321 plasma protein groups at 349 timepoints in 50 critically ill patients receiving invasive mechanical ventilation revealed 14 proteins that showed trajectories different between survivors and non-survivors. A predictor trained on proteomic measurements obtained at the first time point at maximum treatment level (i.e. WHO grade 7), which was weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81). We tested the established predictor on an independent validation cohort (AUROC 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that plasma proteomics can give rise to prognostic predictors substantially outperforming current prognostic markers in intensive care.Peer reviewedFinal Published versio

    Political Islam and grassroots activism in Turkey : a study of the pro-Islamist Virtue Party's grassroots activists and their affects on the electoral outcomes

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    This thesis presents an analysis of the spectacular rise of political Islam in Turkey. It has two aims: first to understand the underlying causes of the rise of the Welfare Party which -later became the Virtue Party- throughout the 1990s, and second to analyse how grassroots activism influenced this process. The thesis reviews the previous literature on the Islamic fundamentalist movements, political parties, political party systems and concentrates on the local party organisations and their effects on the party's electoral performance. It questions the categorisation of Islamic fundamentalism as an appropriate label for this movement. An exploration of such movements is particularly important in light of the event of 11`x' September. After exploring existing theoretical and case studies into political Islam and party activism, I present my qualitative case study. I have used ethnographic methodology and done participatory observations among grassroots activists in Ankara's two sub-districts covering 105 neighbourhoods. I examined the Turkish party system and the reasons for its collapse. It was observed that as a result of party fragmentation, electoral volatility and organisational decline and decline in the party identification among the citizens the Turkish party system has declined. However, the WP/VP profited from this trend enormously and emerged as the main beneficiary of this process. Empirical data is analysed in four chapters, dealing with the different aspects of the Virtue Party's local organisations and grassroots activists. They deal with change and continuity in the party, the patterns of participation, the routes and motives for becoming a party activist, the profile of party activists and the local party organisations. I explore what they do and how they do it. The analysis reveals that the categorisation of Islamic fundamentalism is misplaced and the rise of political Islam in Turkey cannot be explained as religious revivalism or the rise of Islamic fundamentalism. It is a political force that drives its strength from the urban poor which has been harshly affected by the IMF directed neoliberal economy policies. In conclusion, it is shown that the WP/VP's electoral chances were significantly improved by its very efficient and effective party organisations and highly committed grassroots activists

    Unraveling the effect of sex on human genetic architecture

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    Sex is arguably the most important differentiating characteristic in most mammalian species, separating populations into different groups, with varying behaviors, morphologies, and physiologies based on their complement of sex chromosomes, amongst other factors. In humans, despite males and females sharing nearly identical genomes, there are differences between the sexes in complex traits and in the risk of a wide array of diseases. Sex provides the genome with a distinct hormonal milieu, differential gene expression, and environmental pressures arising from gender societal roles. This thus poses the possibility of observing gene by sex (GxS) interactions between the sexes that may contribute to some of the phenotypic differences observed. In recent years, there has been growing evidence of GxS, with common genetic variation presenting different effects on males and females. These studies have however been limited in regards to the number of traits studied and/or statistical power. Understanding sex differences in genetic architecture is of great importance as this could lead to improved understanding of potential differences in underlying biological pathways and disease etiology between the sexes and in turn help inform personalised treatments and precision medicine. In this thesis we provide insights into both the scope and mechanism of GxS across the genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK Biobank. We found small yet widespread differences in genetic architecture across traits through the calculation of sex-specific heritability, genetic correlations, and sex-stratified genome-wide association studies (GWAS). We further investigated whether sex-agnostic (non-stratified) efforts could potentially be missing information of interest, including sex-specific trait-relevant loci and increased phenotype prediction accuracies. Finally, we studied the potential functional role of sex differences in genetic architecture through sex biased expression quantitative trait loci (eQTL) and gene-level analyses. Overall, this study marks a broad examination of the genetics of sex differences. Our findings parallel previous reports, suggesting the presence of sexual genetic heterogeneity across complex traits of generally modest magnitude. Furthermore, our results suggest the need to consider sex-stratified analyses in future studies in order to shed light into possible sex-specific molecular mechanisms

    Probing the Intergalactic medium properties using X-ray absorption from multiple tracers

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    Based on the Lambda Cold Dark Matter concordance cosmological model (ΛCDM), the majority of baryons exist in the Intergalactic medium (IGM). It is extremely challenging to observationally trace the IGM, especially at higher temperatures and low densities. Post reionisation, the vast majority of hydrogen and helium is ionized in the IGM and therefore, the observation of metals is essential for parametrising the IGM properties. My hypothesis is that there is significant absorption in the diffuse highly ionisied IGM and that this IGM column density increases with redshift. I use X-ray absorption in multiple tracers which yields information on the total absorbing column density of the matter between the observer and the source. Clear IGM detections require tracer sources that are bright, distant, and common enough to provide a good statistical sample of IGM lines of sight (LOS). To more accurately isolate any IGM contribution to spectral absorption, I examine each tracer host type to realistically model it, in addition to using appropriate intrinsic continuum curvature models. I test the robustness of the result from a number of perspectives. I examine the impact of the key underlying assumptions that affect the column density calculations including metallicity, ionisation and location of absorption. I look for any evidence of evolution in the parameters. In Chapters 2, 3, 4 and 5, I use gamma-ray bursts (GRBs), blazars and quasars (QSOs) to estimate IGM baryon column densities, metallicity, temperature, ionisation parameters and redshift distributions. My results for each tracer are presented in each of the respective chapters and collectively in Chapter 5 which includes comparative analysis. In conclusion, through the work in this thesis I demonstrate a consistent case for strong X-ray absorption in the IGM on the LOS to three different tracer types and that it is related to redshift. The results are consistent with the ΛCDM model for density, temperature and metallicity. Given these results, I would recommend that studies of distant objects should not follow the convention of assuming all X-ray absorption in excess of our Galaxy is attributed to the host galaxy, that the host is neutral and has solar metallicity. Instead, particularly at higher redshift, absorption in the IGM should be accounted for to give more accurate results for the tracer host properties

    A productive response to legacy system petrification

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    Requirements change. The requirements of a legacy information system change, often in unanticipated ways, and at a more rapid pace than the rate at which the information system itself can be evolved to support them. The capabilities of a legacy system progressively fall further and further behind their evolving requirements, in a degrading process termed petrification. As systems petrify, they deliver diminishing business value, hamper business effectiveness, and drain organisational resources. To address legacy systems, the first challenge is to understand how to shed their resistance to tracking requirements change. The second challenge is to ensure that a newly adaptable system never again petrifies into a change resistant legacy system. This thesis addresses both challenges. The approach outlined herein is underpinned by an agile migration process - termed Productive Migration - that homes in upon the specific causes of petrification within each particular legacy system and provides guidance upon how to address them. That guidance comes in part from a personalised catalogue of petrifying patterns, which capture recurring themes underlying petrification. These steer us to the problems actually present in a given legacy system, and lead us to suitable antidote productive patterns via which we can deal with those problems one by one. To prevent newly adaptable systems from again degrading into legacy systems, we appeal to a follow-on process, termed Productive Evolution, which embraces and keeps pace with change rather than resisting and falling behind it. Productive Evolution teaches us to be vigilant against signs of system petrification and helps us to nip them in the bud. The aim is to nurture systems that remain supportive of the business, that are adaptable in step with ongoing requirements change, and that continue to retain their value as significant business assets

    Theorising Christian Anarchism A Political Commentary on the Gospel

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    This thesis argues that there is a tradition in political theology and in political theory that deserves to be called "Christian anarchism." The various thinkers that contribute to this tradition have never before been considered to be part of a theoretical movement or tradition, and the originality of this thesis is to weave these thinkers together and present a generic theory of Christian anarchism. . Taken together, thinkers like Tolstoy, Ellul, Elliott and Andrews put forward a comprehensive exegesis of Jesus' teaching and example as implying a critique of the state and a vision of a stateless society. Based on this understanding of the Gospel, they accuse both the state and the church of contradicting, betraying and corrupting the essence of Christianity. Some Christian anarchists - Eller in particular - even see Romans 13 and the "render unto Caesar" passage as not discrediting but indeed confirming their interpretation, and although more activist Christian anarchists sometimes disagree on the potential role of civil disobedience, they do all stress that what matters above all is obedience to God Moreover, they all call for the "true" church to lead the Christian anarchist revolution by example, despite the very demanding sacrifices which this involves. They point to numerous examples of similar witness ever since the early church, and themselves strive to emulate such examples in their own lives - the Catholic Worker movement being perhaps the most notable example in this regard Thus, Christian anarchist thinkers' critique of the current order and appeal to follow God's radical commandments echoes the voices of the prophets of old, calling society to return to God's covenant. By weaving their scattered voices together - by theorising Christian anarchism - this thesis provides a political commentary on the Gospel which contributes as much to political theory as it does to political theology
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