250 research outputs found
Peace photographies:A short introduction
No full textTom Allbeson is Reader in Media and Photographic History at the School of Journalism, Media and Culture (Cardiff University, UK) and co-editor of the Journal of War and Culture Studies. His research concerns media history and visual culture in contemporary Europe with specialisms in photojournalism and conflict, visual culture and reconstruction, collective memory in post-conflict societies, and urban history. He is the author of Photography, Reconstruction and the Cultural History of the Postwar European City (Routledge, 2020) and co-author of Conflicting Images: Histories of War Photography in the News (Routledge, 2024).Pippa Oldfield is Senior Lecturer in Photography at Teesside University, UK, and former Head of Programme at Impressions Gallery, Bradford. She is the author of Photography and War (2019) and has curated numerous exhibitions on the topic of conflict and its aftermath, including Bringing the War Home: Photographic Responses to Recent Conflict in Iraq and Afghanistan and No Man’s Land: Women’s Photographic Viewpoints on the First World War...
Hidden Women: uncovering the veil of silence during the partition of Punjab
No full textDr Pippa Virdee of De Montfort University uncovers the hidden voices of Muslim women during the partition of the Punjab, India in 1947. Using first-hand accounts, Dr Virdee reveals how women, often sheltered from private and public spaces, created their own space during this complex and traumatising time.
This talk was part of The National Archives’ Diversity Week, a series of events and activities aimed at promoting equality and diversity in how we work and what we do.http://media.nationalarchives.gov.uk/index.php/author/dr-pippa-virdee
Investigating the role of orphan GPR50 in normal brain function and mental illness
No full textG protein-coupled receptors (GPCRs) form a link between the cell and their
environment when signaling pathways are activated upon ligand binding. However,
the ligands and functions for many GPCRs remain to be determined. G protein-coupled
receptor 50 (GPR50) is one such orphan, and its exact role is yet unknown.
There is however emerging functional and genetic evidence suggesting a function for
GPR50 in psychiatric illness and lipid metabolism. It was hypothesised that
investigating GPR50’s protein-protein interactions would lead to a greater
understanding of the role of GPR50 in normal brain functioning and in mental
illness. Putative protein interactors were initially isolated by a yeast two-hybid study
and were further tested here. To address GPR50’s links to mental illness, the
GPR50∆502-505 deletion variant associated with mood disorders was also investigated.
To test this hypothesis I sought to confirm some of the key yeast two-hybrid
interactions. Using co-immunoprecipitation and immunocytochemistry the
interaction of GPR50 with reticulon family members Nogo-A, Nogo-C and RTN3,
and with cell-cell adhesion molecule CDH8 and lipid-associated protein ABCA2
were validated.
In order to identify the location of interactions, subcellular fractionation of mouse
brain and rt-PCR and immunohistochemistry in developing and adult mouse brain
were performed. GPR50 and several interactors were found to be enriched at the
synapse by subcellular fractionation of whole adult brain, and at embryonic day 18
(E18) and 5 weeks by rt-PCR. Colocalisation of GPR50 and interactors was found in
the amygdala, hypothalamus, cortex and specific brain stem nuclei by
immunohistochemistry. The discovery of GPR50 expression in noradrenergic,
serotonergic and dopaminergic nuclei in the adult brain stem suggests a further role
for GPR50 in neurotransmitter signaling and stress.
To investigate the function of GPR50 two assays were performed that measure
processes which are known to be affected by Nogo and RTN3: The first assay was a
neurite outgrowth assay in Neuroscreen-1 cells, a PC12 cell clone. A significant
increase in neurite length was detected after transient overexpression of GPR50 and
this effect was increased in the GPR50∆502-505/T532A variant. Additionally GPR50-overexpression resulted in an increase in filopodia formation suggesting a role in
actin dynamics. As a second functional assay in vitro BACE1 activity assays were
performed in HEK293 cells. GPR50 but not GPR50∆502-505/T532A overexpression
resulted in a significant increase in BACE1 activity.
Lastly a final series of pilot experiments were performed to gain insight into the
secondary structure of the C-terminal domain and the effects of the polymorphisms
on structure. The 35kDa GPR50 C-terminal domain was purified and Circular
Dichroism studies indicated a predominantly unstructured protein with increased a-
helical content in the GPR50∆502-505 variant.
The results in this thesis indicate a role for GPR50 in neuronal development and
synaptic functioning. The results also strengthen an association with major mental
illness, with links to several disease mechanisms
Felon Disenfranchisement and the History of Women’s Voting Rights
No full textPippa Holloway is the Douglas Southall Freeman Chair in History at the University of Richmond. She is the author of Living in Infamy: Felon Disfranchisement and the History of American Citizenship (2014) and Sexuality, Politics, and Social Control in Virginia, 1920–1945 (2006). She is also the editor of Other Souths: Diversity and Difference in the U.S. South, Reconstruction to Present (2008). Her research on felon disfranchisement was supported, in part, by a Soros Justice Fellowship from the Open Society Foundations. She teaches courses in U.S. history, focusing on southern history, incarceration, LGBT history, and historical research methods. Her current research examines the right of those charged with crimes or convicted of felonies to testify in court.
This event was sponsored by the College of Arts and Sciences, the Center for the Humanities, and the Suffrage Centennial Committee
Elizabeth Beachbard (c.1822–1861): America’s First Woman War Photographer?
No full textDr. Pippa Oldfield, Senior Lecturer in Photography, Teesside University, United Kingdom
Elizabeth Beachbard (c.1822–1861): America’s First Woman War Photographer?
The history of war photography has been dominated by men. Feminist photo historians have challenged this view, bringing to light outstanding women such as Gerda Taro in the Spanish Civil War and Lee Miller in the Second World War. Miller’s and Taro’s frontline photojournalism fits the masculinist canon of “authentic” war photography, but this mode has excluded most women. What happens if we go beyond the limits of the genre? Who else might come into view?
In this paper, I present the first dedicated research into Elizabeth Beachbard, a forgotten photographer who worked in Louisiana during the American Civil War (1861–1865). I chart her trajectory from an ambrotype portrait studio in New Orleans to a makeshift cabin in a military camp in rural Louisiana, where she photographed Confederate soldiers during the summer of 1861. It\u27s a tale of twists and turns, including court cases, bigamy, a measles epidemic, and a devastating fire. One of my biggest finds is new evidence for an ambrotype hitherto unattributed to Beachbard, which constitutes only the third surviving example of her work.
While questions of gender are central to my paper, I shall not be arguing for essentialist notions of “feminine” photography. Instead, I highlight the gendered constraints of the epoch showing how Beachbard navigated social, political, economic and legal structures. It is ironic that portraiture, one of the few professions open to “respectable” women, was how Beachbard entered the masculine territory of a wartime army camp.
Elizabeth Beachbard could not be considered a war photographer in the conventional sense. Nonetheless, she worked in a military arena, made pictures of soldiers in wartime, and lost her life in the activity. She should be seen as a pioneering figure in the history of women’s photography: perhaps, even, as America’s first woman war photographer.
Dr. Pippa Oldfield is a curator and photo-historian with research specialisms in photography, gender and conflict. She is Senior Lecturer in Photography at Teesside University, UK, and former Head of Programme at Impressions Gallery, one of the UK’s leading photography spaces. Pippa has curated numerous touring exhibitions including ‘No Man’s Land: Women’s Photography and the First World War’ (2017-2019). She is the author of Photography and War (Reaktion 2019) and is currently working on her new monograph, Ungentle Camera: War and Women’s Photography for University of Texas Press
Genome wide gene expression analysis of two ENU mouse models of major mental illness
No full textMajor mental illness is now recognised as one of the leading causes of adult
morbidity. Of the adult onset psychiatric disorders, the functional psychoses
(schizophrenia, bipolar disorder and recurrent major depression) are the most severe
and most common in the general population. Evidence suggests that certain genetic
factors influence an individual’s susceptibility to developing these disorders when
combined with appropriate social and environmental conditions. Several good
candidate genes have been identified. Of relevance to this study is Disrupted in
Schizophrenia 1 (DISC1) which was identified in a large Scottish family that carried a
balanced translocation (t1:11) and had a history of major mental illness. In 2008, two
ENU mutant mouse models with missense mutations in exon 2 of Disc1 were
characterised and found to have behavioural and neuroanatomical phenotypes
consistent with schizophrenia and major depression. The primary aim of this thesis is
to further analyse these mouse models by performing whole genome gene expression
studies and secondary protein analysis to identify genes involved in the aetiology of
schizophrenia and major depression.
My initial analysis used Illumina BeadChip microarray technology to identify 368
genes that were differentially expressed in ENU mutant animals under different
biological conditions, compared to appropriate control animals. Nine biological
groups were compared including one embryonic group at E13, and three groups
treated with appropriate anti-psychotic or anti-depressant drugs. Of the 368 genes
identified as differentially expressed, 46 were chosen for validation by qRT-PCR
based on fold-change, p-value, functional significance, overenrichment of GO terms,
pathway analysis and previous implications in major mental illness. NRXN1, NRXN3
and CDH11 were found to be significantly up-regulated in the schizophrenia mouse
model with EGR4 significantly down-regulated compared to C57BL/6J wild-type
controls. These findings were also replicated in an independent sample using wildtype
littermates. The mental retardation gene PAK3 was up-regulated in the
schizophrenia mouse model and expression levels were corrected to a level not
significantly different to wild-type, when treated with the PDE4 inhibitor Rolipram.
Semi-quantitative western blotting also confirmed the disregulation of EGR4 and
PAK3 at the protein level in these animals. RNA expression profiles were also
characterised for each of the genes above, and DISC1, through development. In summary this thesis describes the striking disregulation of four prominent genetic
candidates of major mental illness in an independent animal model. A first functional
link between DISC1 and NRXN1 is described suggesting, for the first time, a DISC1-
dependant mechanism for regulating neurexin gene expression
Evoking the Possibility of Presence:Textual and Ideological Effects of Linguistic Negation in Written Discourse
No full textThis thesis explores the textual and ideological effects of linguistic negation in written texts. It argues that when language users process negation, understanding its use in context is as much about the possibility of presence as it is about the actuality of absence. This gives rise to a variety of effects in texts from contributing to the construction of fictional characters to potentially influencing readers’/hearers’ view of the world they inhabit. This thesis brings together research on the theoretical aspects of how negation works to present a new approach to linguistic negation in written discourse. It also demonstrates how this approach can be applied in the analysis of the conceptual practice of negating. The approach presented is made up of three main elements; negation is presuppositional, is realised through a wide variety of linguistic forms beyond the morphosyntactic core forms (not, no, never, none, un-, in-, and so on) and includes semantic and pragmatically implied forms. These two elements combine to give rise to implied meaning in context. Having outlined this approach to negation, it is then applied in the analysis of literary and non-literary texts to explain the textual and ideological effects that arise from its use
Characterising the role of GPR50 in neurodevelopment and lipid metabolism
No full textG-protein coupled receptor 50 (GPR50) is a genetic risk factor for psychiatric illness.
It is a member of the melatonin receptor family, which includes the well
characterised melatonin receptors 1 and 2 (MT1 and MT2). However, the ligand for
GPR50 remains elusive and little is known about GPR50 signalling pathways.
Despite this, GPR50 is known to enhance neurite outgrowth and inhibit the actions of
the neurite outgrowth inhibitor NOGO-A. Existing evidence also indicates a role in
lipid metabolism; GPR50 knockout mice displayed abnormalities in energy
homeostasis and weight control, whilst sequence variants are associated with altered
lipid levels in humans. Further, a yeast-2-hybrid screen identified SREBF2 and
ABCA2, regulators of lipid homeostasis, as GPR50 interactors. This thesis explores
the role of GPR50 in neuronal development and lipid metabolism.
The work presented in this thesis shows that GPR50 promotes neuronal
differentiation. Overexpression significantly increased the number of neurites per
cell in SH-SY5Y cells. Further, dendritic branching was enhanced by GPR50
transfection in hippocampal and cortical neurons (DIV 14). In hippocampal neurons,
GPR50 transfection also lead to a shift towards spine maturity although it had no
effect on spine morphology, suggesting GPR50 enhances spine development but may
not alter synaptic strength. The effect of GPR50 on neuronal morphology may be
driven by actin remodelling. Immunocytochemistry showed an enrichment of
GPR50 in highly dynamic regions of the membrane, i.e. the lamellipodia and
dendritic spines. Overexpression in SH-SY5Y cells also resulted in an increase in
WAVE-2 and phosphorylated RAC1/CDC42, key modulators of actin dynamics.
Additionally, GPR50 transfection altered the protein level and localisation of α-
catenin, another regulator of actin organisation, in HEK293 and SH-SY5Y cells
respectively. An involvement of GPR50 in lipid metabolism has also been demonstrated in this thesis. Verification of the Y2H study suggested GPR50 does not physically interact
with SREBF2 or ABCA2. However, ABCA2 appears to induce the intracellular
localisation of GPR50 in several cell lines. In SH-SY5Y cells, this was mimicked by
the inhibition of cholesterol trafficking, suggesting the translocation of GPR50 to the
plasma membrane is dependent on cholesterol transport. Further, the depletion of
lipoproteins resulted in the downregulation of GPR50, indicating a responsiveness to
lipid levels. Finally, GPR50 increased lipid metabolism, as seen by a decrease in
intracellular lipid droplets upon GPR50 overexpression.
The data presented here extends previous work indicating a role of GPR50 in
neurodevelopment. It also highlights a potential mechanism by which GPR50
regulates neuronal morphology, i.e. via actin remodelling. Reports that GPR50 is
involved in energy homeostasis is also supported in this thesis, further, results
presented here suggest GPR50 is specifically involved in lipid metabolism. These
processes are often disrupted in mental illness, thus this work may provide a
functional link between GPR50 and psychiatric disorders
Genetic responses to environmental stress underlying major depressive disorder
No full textMajor depressive disorder (MDD) is a common psychiatric disorder and a
leading cause of disability worldwide. Such illness is the result of a complex
interplay between genetic susceptibility and environmental risk factors.
Adverse life events are experienced before the onset of depressive episodes
in most patients, with robust evidence for the role of stressful life events
(SLE) as a main trigger of depressive symptoms. However, not all individuals
develop depression after episodes of stress. Thus, an individual’s sensitivity
to stress is an important predictor of stress response that may mediate the
association between stress and depression. A deeper understanding of the
genetic mechanisms underlying stress-sensitivity and stress response is,
therefore, crucial to a better understanding of MDD and thus to improve
treatments for both depressive symptoms and other stress-related conditions.
This PhD thesis uses empirical data from white Caucasian population-based
samples. By incorporating in new hypothesis-free genome-wide association
studies and polygenic approaches quantitative measures of recent SLE and
neuroticism---a personality trait though to mediate or moderate the effects of
adversity on depression risk---, this PhD thesis identifies the genetic
influences to a proxy for sensitivity to environmental stress and genotype-byenvironment
interaction (GxE) effects underlying depressive symptoms.
Following an introductory chapter, chapter 2 conceptualizes a proxy for our
sensitivity to negative outcomes by modelling the interaction between genetic
variants and MDD status on neuroticism score through a genome-wide
interaction study. This chapter seeks to identify genetic variants contributing
to a potential endophenotype mediating the associations between stress and
depression, and examines whether genetic effects on such proxy for stress
sensitivity partially explains the genetic contributions to liability not
attributable to additive main effects. The strongest signals came from genetic
variants associated with the glucocorticoid receptor function. Therefore,
Chapter 3 assesses the enrichment of the genetic contributions to liability of
MDD within three glucocorticoid-related gene sets: one gene set reflecting
“up-stream” cortisol signalling genes and two gene sets reflecting “downstream”
cortisol response genes. Chapter 4 empirically tests and assesses
the diathesis-stress theory for depression; using polygenic risk scores
weighted by the additive effects of MDD derived from the Psychiatric Genetic
Consortium MDD genome-wide association study and self-reported
measures on recent SLE. This chapter provides evidence for the presence of
GxE effects between stress and common genetic variants on risk of
depressive symptoms. The empirical support for this theory validates other
GxE approaches applying a genome-wide approach to investigate the
causative effect of stress in the development of depressive symptoms. Thus,
chapter 5 presents findings from genome-wide by environment interaction
studies in two cohorts that seek to identify common variants displaying an
increased risk of liability to depressive symptoms in response to SLE.
Whether inclusion of GxE effects improves the prediction of liability to MDD
over that explained by genetic additive main effects alone is also tested.
Furthermore, two potential forms of gene-environment interplay (i.e. GxE and
gene-environment correlation) and their biological interpretation are
extensively discussed. Stress contributes to many human conditions.
Therefore, the GxE effects are also used to predict other stress-related
physical and mental conditions. This chapter reports evidence of a potential
shared aetiology between depression and other traits, such as schizotypal
personality or heart disease, due to genetic mechanism underlying the
effects of SLE. Finally, chapter 6 brings back the diathesis-stress model
investigated in chapter 4. This chapter incorporates into the diathesis
framework the genetics effects for stress sensitivity and stress response
estimated in chapters 2 and chapter 5, respectively, and assess their
relevance to the diathesis-stress theory. Genetic differences between women
and men in stress response underlying the aetiology of depression are also
discussed.
Genetics plays a significant role in the effects of stress. The findings
presented in this thesis emphasize the relevance of genetic effects for stress
sensitivity and stress response in depression and health in general. Overall,
this thesis presents a range of original studies in order to advance our
understanding of the genetic response to stress, comprehensively discussing
the limitations and pitfalls of this research area, and provides a basis for
future lines of research on gene-environment interplay in psychiatry
Using DNA methylation data and haplotypes to investigate predisposition to Alzheimer’s disease
No full textAlzheimer’s disease (AD) is a complex neurodegenerative disease resulting in cognitive decline, memory issues and alterations in mood, behaviour, and personality. AD is the most common form of dementia, which accounts for 50-75% of cases globally. Individuals with AD may become impulsive and disorientated in the early stages but as the disease progresses many require full time care support and die prematurely. AD pathophysiology is characterised by amyloid-beta plaques and tau neurofibrillary tangles within the brain. AD has a high heritability (60-80%) yet much of this remains largely unexplained. There are predicted to be between 100-10,000 causal variants; exemplifying the necessity to identify and characterise new genetic risk factors. In some cases, epigenetic changes in the genome may be studied to provide additional understanding into the effect the heritable risk of AD has on gene expression. Epigenetic changes may be investigated using polygenic risk scores (PRS) and epigenome wide association studies (EWAS), which may provide insight into an individual’s genetic susceptibility to AD and the association between AD and DNA methylation. Previously, Walker et al used 26 lead loci to identify 68 significant differentially methylated (DM) CpGs. Walker et al carried out meQTL analyses using the DM CpGs identified, finding 48 CpGs were associated in cis with genetic variants in the genome wide association study (GWAS) loci. The aim of the study was to use additional AD associated loci to identify and characterise further genome wide significant (GWS) DM loci, using individual SNPs and haplotypes. Additionally, the individual effects of functional haplotypes on epigenetic variation were investigated. The most recent and relevant AD-GWAS results were used in this study, with up to 75 AD risk loci identified, to generate an AD PRS. The AD PRS were used to identify significant AD associated, DM CpGs. meQTL analysis was carried out to investigate the association of the significant CpGs with the SNPs in the PRS. SORL1 and APOE have previously been identified as AD susceptibly genes, and functional studies have been carried out. The functional studies have identified SNPs within APOE and SORL1 which directly influence the function of the genes and protein production, altering an individual’s risk to AD. Therefore, haplotypes spanning these gene regions were used in meQTL analyses to consider whether the individual SNPs or haplotypes have a different association with DM at the significant CpGs. Further EWAS were carried out using only haplotypes which contain the AD-risk allele at the SNPs comprising the functional haplotype in SORL1 and APOE. Schwartzentruber et al and Bellenguez et al AD GWAS were identified as the most suitable for the PRS generation. EWAS meta-analyses using the Bellenguez et al and Schwartzentruber et al derived PRS identified 116 and 203 GWS DM CpGs, respectively. meQTL analyses identified 45/116 and 109/203 of these GWS CpGs were significantly associated with SNPs in the PRS.
With 31 and 21independant GWS lead CpGs identified using the Bellenguez et al and Schwartzentruber et al PRS in the EWAS, respectively. meQTL analysis found SNPs in the SORL1 region had the strongest association with DM at CpG sites, as opposed to haplotypes and/or when the APOE region were investigated.
Functional haplotypes dependent upon carrier status identified additional GWS DM CpGs and associated genes, of particular interest was FEM1C. Ultimately this study may allow further investigation into the importance and relevance of the GWS DM loci in AD progression, disease pathogenesis and aetiology
- …
