3,016 research outputs found
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
Belonging: natural histories of place, identity and home
No full textCanongate's synopsis:
"Reflecting on family, identity and nature, Belonging is a personal memoir about what it is to have and make a home. It is a love letter to nature, especially the northern landscapes of Scotland and the Scots pinewoods of Abernethy – home to standing dead trees known as snags, which support the overall health of the forest.
Belonging is a book about how we are held in thrall to elements of our past. It speaks to the importance of attention and reflection, and will encourage us all to look and observe and ask questions of ourselves.
Beautifully written and featuring Amanda Thomson’s artwork and photography throughout, it explores how place, language and family shape us and make us who we are."
Longlisted for the Highland Book Prize, 2023
Some of the reviews...
Outstanding - ROBERT MACFARLANE
Amanda Thomson’s new book manages to carve out a distinctive niche for itself . . . This is a passionate book and infused with a sense of rootedness - STUART KELLY, The Scotsman
In recent years rural landscapes have turned into battlegrounds, and nature writing has become increasingly polemical. Belonging is a quiet book of questions in a genre full of answers, but it is all the more powerful and beautiful for this - PATRICK GALBRAITH, TLS
One of the best things I have read in ages . . . Quiet and beautiful and powerful - ALYS FOWLER
Thomson writes of the natural in a way I have yet to encounter before. There is no real hoo-haa, no flowery description of which to speak yet somehow, I came away with that ache inside me — that renewed obsession with the world that is only borne of a very particular kind of writing — poetic, loving, raw . . . Like no other - KERRI Ní DOCHARTAIGH, Caught by the River
In strikingly original takes on Scottish history, environmentalism, Black feminist theory, artmaking, list-making, memory, and memoir, Thomson crafts a cadence that is as wise as it is vitally alive. - MARGOT DOUAIHY, author of Scorched Grac
Kathleen Jamie, Chitra Ramaswamy & Amanda Thomson: Antlers of Water - Live Event
No full text‘When we read and write, when we love our fellow creatures, when we walk on the beach, when we just listen and notice, we are not little cogs in the machine, but part of the remedy.’ These luminous words by Kathleen Jamie form part of the introduction to Antlers of Water, an outstanding collection of contemporary Scottish writing about nature and landscape.
The generosity of Jamie’s approach as editor of the collection goes beyond the stellar selection of contributors such as Amy Liptrot, Karine Polwart and Malachy Tallack: she also invokes the agency of readers to make a difference. ‘If, by reading, you are encouraged or confirmed in your love of the natural world, if you’re inspired simply to… look outside, then our job is done.’
In a discussion led by the BBC's Clare English, Jamie is joined by award-winning journalist Chitra Ramaswamy as well as visual artist and writer Amanda Thomson – both contributors to the anthology – to discuss Scotland, landscape and the more-than-human world around us.
This is a live event, with an author Q&A.
Part of the Edinburgh International Book Festival Making Climate Change Personal festival theme
Figures of Speech: Place - Amanda Thomson and Roseanne Watt
No full textEvent as part of Scotland's Year of Stories 2022, Edinburgh City of Literature & the Scottish Storytelling Centre present figures of speech. " ... Our hosts Amanda Thomson and Roseanne Watt take us on a tour through nature, landscape, community and the language of place, whilst also discussing their own experiences of writing and working in Scotland."
Figures of Speech: place. One of a series of events covering six universal themes (music, friendship, future, love, place, big ideas), each event explores literary blockbusters, hidden gems and modern classics.
Our expert guides will take us on a journey through Scotland’s iconic books and stories, navigating the dazzling array of new voices, and presenting newly commissioned work by artists responding to each theme.
'Let us take you on a journey across the curious contrasts and contradictions that define Scottish literature.
In our first season (May - July), we'll be covering Music, Friendship and Future. On May 20th writer and broadcaster Nicola Meighan and author Arusa Qureshi will be exploring Music, and presenting a newly commissioned dance piece from poet and performer Katie Ailes. Poet Michael Pedersen and author Val McDermid will be diving into Friendship on June 24th, with music from Kim Carnie. And on July 22nd, poet Russell Jones and writer T.L.Huchu will be looking to the Future, with new poetry from Jeda Pearl.
The second season of Figures of Speech (September - November) will take in Love, Place and Big Ideas. On September 23rd Gaelic poet Peter Mackay will talk love with romance writer Jenny Colgan. Visual artist and writer Amanda Thomson will drop a pin in the literary map with a discussion on Place with poet and film maker Roseanne Watt on October 21st (postponed to February '23). The season concludes on St. Andrew’s Day (November 30th) with some Big Ideas from Professor David Farrier with activist and author Jessica Gaitán Johannesson.
We want to welcome as wide an audience as possible and extend this conversation across Edinburgh, Scotland and the world. All the events will be recorded and made available online a week later, and both the live and recorded events will be supported by BSL interpretation.
Joule-Thomson Expansion of Gas-Condensates: Literature review
No full textRecently it was communicated that during gas-condensate production in a North Sea gasfield strong heating of the production stream occurred instead of the expected cooling. This contradictory behaviour called for an investigation of the thermodynamics of these gas condensate reservoirs. It is expected that due to the high pressure and high temperature conditions in these gas-condensate reservoirs (pressures of approximately 1000 bar and temperatures of 100-200 °C), the Joule-Thomson coefficient will have a negative value and thus heating will take place at expansion; this is called the Joule-Thomson inversion effect. To ensure a safe operation and to ensure that downhole and surface equipment is specified according to downhole temperatures, it is required that pressure and temperature profiles can be accurately estimated for future productions. The present work is a literature review of what has been reported in the open literature with respect to the Joule-Thomson inversion effect and the heating of gas-condensates at expansion. Chapter 2 will give a general introduction to the Joule-Thomson effect. In chapter 3 the various methods of how to characterize the inversion curve are described and chapter 4 will discuss the calculation of the temperature changes due to expansion. The gas-condensate systems are dealt with in chapter 5 and finally in chapter 6 a summary is given and different aspects, which are important to predict temperature changes for gas-condensate systems, are considered.Applied SciencesApplied Thermodynamics and Phase Equilibri
Death Writes: Microbursts & The Clearing: a discussion on text, subject and craft with Elizabeth Reeder and Amanda Thomson - collaborators on microbursts and with Samantha Clark author of The Clearing
No full textDeath Writes is part of the University of Glasgow's interdisciplinary Arts-Lab, Reading and Writing Death and Dying.
Elizabeth Reeder, Amanda Thomson (collaborators on Microbursts) and Samantha Clark (author of The Clearing) will read and talk about their books and the writing, design and editorial processes they underwent. Both books deal with the intense time of being within parental illness, and consider experiences of illness, mental health, parental death, and various types of grief in ways that weave through and utilise artistic and multi-modal processes
Henri Temianka Correspondence; (thomson)
No full textThis collection contains material pertaining to the life, career, and activities of Henri Temianka, violin virtuoso, conductor, music teacher, and author. Materials include correspondence, concert programs and flyers, music scores, photographs, and books.https://digitalcommons.chapman.edu/temianka_correspondence/4209/thumbnail.jp
Joule-Thomson Expansion of Gas-Condensates: Predictions using Equations of State
No full textThis work deals with the Joule-Thomson expansion of high-pressure high-temperature gascondensates. After observing unexpected heating of the produced condensate at pressure relief in a North Sea gas-condensate reservoir, it seemed to be necessary to investigate the possibility of the Joule-Thomson inversion effect to occur in these reservoir fluids. No experimental data is available on Joule-Thomson effects in gas-condensate reservoirs and, therefore, this work has an entirely theoretical basis. Calculated Joule-Thomson coefficients, inversion curves, and isenthalpic lines for some lighter constituents of gascondensate mixtures, e.g. nitrogen, carbon dioxide, and methane, were compared with experimental data to get insight in the applicability of cubic equations of state. The equations used are the Redlich-Kwong, the Soave-Redlich-Kwong and the Peng-Robinson equations of state...Applied SciencesChemical Technology and Materials ScienceApplied Thermodynamics and Phase Equilibri
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
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
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