VictorJuiz/thesis huggingface dataset:
Structure and function of trimeric intracellular cation channels (TRIC) and ryanodine receptors (RyR)

Controlled Ca2+-release from the sarcoplasmic reticulum (SR) during excitation-contraction coupling (EC-coupling) is essential for cardiac and skeletal muscle contraction. Ca2+ is released through ryanodine receptors (RyR) in the SR membrane but there are other, different types of ion channels in the SR with unclear physiological roles, and some of these channels have not been identified. In this thesis, I have investigated the structural and biophysical properties of certain ion channels found in the SR, including SR K+ channels, trimeric intracellular cation channels (TRIC-A and B) and RyR.
The gating and single-channel conductance of SR ion channels was examined after incorporation of vesicles of SR into planar phospholipid bilayers under voltage-clamp conditions. In the search for a ligand that binds to the SR K+ channel, I found that ebselen irreversibly inhibited the channel and that dithiothreitol could partly reverse this effect suggesting the ebselen modified cysteine residues on the channel.
It is suggested that TRIC-A or TRIC-B could be the SR K+ channel and so I investigated this by characterising the biophysical properties of the ion channels observed after incorporating membrane vesicles obtained from HEK293 cells co-expressing RyR2 plus TRIC-A or RyR2 plus TRIC-B into bilayers. My results indicated that TRIC-A and TRIC-B are non-selective ion channels, permeable to both Cl- and K+, and therefore are unlikely to be SR K+ channels which are highly selective for monovalent cations. I also found that co-expression of TRIC-A or TRIC-B with RyR2 altered the response of RyR2 to cytosolic Ca2+ suggesting that both TRIC-A and TRIC-B interact with RyR2 to regulate RyR2 gating.
I established a cardiac-specific Tric-a knockout (Tric-a-cKO) mouse colony as a platform to explore the physiological roles of TRIC channels in the heart. The colony was validated by mRNA and protein levels of other ion channels present in mice hearts.
Using homology modelling, I also studied the putative structural changes to RyR2 caused by the mutations V2475F and R2474S that are associated with the lethal arrhythmic disease, catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1). The predicted models suggested that there are significant conformation changes to the RyR2 helical domain1, thus providing new information regarding the relationship between structural and function in CPVT1.

Keywords: catecholaminergic polymorphic ventricular tachycardia
EC-coupling
ion channel
Ryanodine receptor
Calcium release
trimeric intracellular cation channel
Advisor: Sigalas, C
Sitsapesan, R
Tammaro, P
The English critical reaction to contemporary painting, 1878-1910

During the period 1878-1910 new criteria for the serious discussion of modern painting were established in England. The first chapter examines some of the differences between the criticism of painting and of literature, looks at the social function of art criticism, and outlines the terms of the crucial debate of these years, between the New Critics and the old guard, characterised by their enthusiasm for form and for content respectively. The second chapter discusses the development of art criticism in England since the first public exhibitions of the eighteenth century; the third examines publications containing such writing, and some of its individual practitioners, during 1878-1910. The task of the critic is then considered, in terms of the conditions of work and the demands which were explicitly placed on him or her. The following two chapters deal with the relationship between art and narration, and between art and morality. Particular attention is paid to the way in which the vocabulary of moral judgment applied to Victorian society in general is transferred to the work of art. Chapter seven discusses the reception of innovatory painting, notably by the Impressionists and Post-Impressionists, and the terms and arguments used by sympathetic critics to render this painting intelligible and acceptable to the general public. In conclusion, it is maintained that throughout the nineteenth and early twentieth centuries, the relationship between the written word and the painted canvas has always been a close one. However, from being primarily descriptive in character, developments in painting, with emphasis shifting from content to form, made criticism far more technical in its concerns. As the use of the written word becomes increasingly essential to an understanding of the visual, so the authority of the critic to prescribe, as well as describe, increased.

Keywords: England
19th century
Art criticism
nineteenth century
twentieth century
contemporary painting
20th century
critical reaction
Advisor: Haskell, F
Richards, B
Butler, C
Patterns and drivers of over-time change in the intergenerational transmission of inequality in Germany and the UK

This doctoral thesis contributes to research on over-time trends in the intergenerational transmission of inequality in two major European societies. Paper 1 entitled ‘Intergenerational Class Mobility of Labour Market Entrants in Germany and the UK since the 1950s’ shows that absolute mobility between parents’ social class and their children’s first social class has continuously changed. Still, increases in relative mobility rates have come to a halt for cohorts entering the labour market from the 1970s onwards in both countries. Paper 2 entitled ‘Why do Trends in Social Fluidity at Labour Market Entry and Occupational Maturity Differ? Evidence from Germany and the UK’ identifies increases in counter mobility as the main driver of observed divergence between trends in relative intergenerational social class mobility based on class destination measured at labour market entry and later career stages. It links the growth in counter mobility to compositional shifts in the origin distribution during the second half of the twentieth century. Paper 3 entitled ‘The Effect of Social Benefit Reform on Educational Inequality’ finds that children of parents receiving long-term unemployment assistance have a lower chance to attend the academic secondary school track compared to children of parents receiving no unemployment or social benefits after the 2005 Hartz reform in Germany. Besides changes in the socio-demographic characteristics of benefit recipients, this rise in educational inequality was mainly due to reductions in benefit levels. Paper 4 entitled ‘Parental Employment and Children’s Education in Historical Perspective’ shows that parental employment conditions have increasingly become economically insecure for cohorts born since the mid-1980s in Germany. No weakening in the positive association between parental employment and children’s education can however be observed.

Keywords: Inequality
Germany
Social mobility
UK
Over-time change
Advisor: Bukodi, E
The transformation of a pastoral economy : Bedouin and states in northern Arabia, 1850-1950

This thesis analyzes economic change among the bedouin of northern Arabia by examining four factors: the trade in camels; intertribal raiding; large-scale attacks by the Akhwan; and trade and smuggling. Many writers have assumed that the sale or hiring of camels for transport by camel-herding tribes was their major source of income, and that the spread of modern transportation caused a decline in the demand for camels, resulting in lower prices for the animals, and an economic crisis for the bedouin. The well-documented case studies in this thesis will show that the transformation of bedouin society in the modern era was more complex.
The first chapter will present an overview of the principal factors that affected bedouin livelihoods during the nineteenth century: the environment, intertribal relations and relations with settled populations. The second chapter examines how the trade in northern Arabian camels changed between 1850 and 1950. It shows that demand for camels rose and fell throughout the period, even as the use of modern modes of transport increased. In fact, from about 1892 to 1914, the sale of thousands of camels from northern Arabia in the markets of Egypt for butcher’s meat accounted for a large portion of the total camel trade in the region. The third and fourth chapters examine in detail the ways in which intertribal raiding, large-scale attacks by Akhwan forces and government policies affected bedouin livelihoods in Kuwait, Iraq and Transjordan between 1920 and 1940. The final chapter demonstrates how growing state power altered bedouin trading patterns during the same period, and how some tribes became involved in smuggling, or were harmed by zealous anti-smuggling measures carried out by government officials.

Keywords: pastoral economy
Bedouin
Arabia
northern Arabia
transformation
Advisor: Rogan, E
Expression of particulate methane monooxygenase (pMMO) proteins in plants for methane detoxification

Methane is a potent greenhouse gas which has contributed to approximately a fifth of global warming since pre-industrial times and its concentration continues to rise yearly in parallel to that of CO2. Anthropogenic activities contribute to 70% of global emissions, with the main sources being the extraction and transport of fossil fuels, farming of livestock, waste management, rice agriculture, and biomass burning. Rice cultivation is a major source of anthropogenic emissions due to the flooded conditions of the soil and presence of organic matter which pose favourable conditions for biotic methanogenesis. In turn, the rice plants transport the greenhouse gas into the atmosphere through the porous aerenchyma tissue in a process termed “the chimney effect”. Strategies for mitigating rice emissions include modifying the watering regimes and the supplementation of organic additives. However, these practices are not always feasible for farmers and may introduce drawbacks such as lower grain yields and the emission of N2O. In this thesis, the bioengineering of rice for methane mitigation is postulated. In nature, methanotroph bacteria use methane as their source of carbon and energy via methane monooxygenase enzymes (MMOs), and predominantly through particulate methane monooxygenase (pMMO). pMMO is encoded in an operon and forms a membrane-bound nonamer complex composed of three different protein subunits. The heterologous expression of pMMO has been deemed challenging due to its membrane localization and copper content. In this work the recombinant expression of pMMO in tobacco and Arabidopsis is presented as a proof of concept, with the further aim of bioengineering rice to contain pMMO and reduce emissions from paddy fields. The pmoC, pmoA and pmoB subunits were targeted to the endoplasmic reticulum (ER) individually, and gene stacking strategies were explored. The use of 2A self-cleaving peptides resulted in a successful gene stacking methodology to express all the subunits in the ER. The 2A pMMO polypeptide expression was greatly enhanced by co-expression with P19, and did not induce major disruption or modification to ER structure and dynamics. This thesis shows, for the first time, that the pMMO proteins can be co-expressed in plant cells without apparent detrimental effects, and strategies for obtaining a functional enzyme in the recombinant system are investigated and discussed.

Keywords: endoplasmic reticulum
particulate methane monooxygenase
Advisor: Fricker, M
The role of lipid-specific CD1a-mediated immune responses in inflammatory disease

CD1a is predominantly expressed by antigen-presenting cells in the skin, where it modulates immune responses through lipid antigen presentation to T cells. Increasing evidence supports a role of regulatory T cells (Tregs) in the control of skin immune programs. However, whether Tregs can recognise CD1a and maintain immune homeostasis remains unstudied.
The first aim of this study was to interrogate the functional interaction of Tregs with CD1a and characterise CD1a-reactive Tregs in health and psoriasis. Here, a subpopulation of polyclonal Tregs (~2%) was found to secrete the immunosuppressive cytokine IL-10, but not skin inflammation-associated cytokines, in a CD1a-dependent manner. Moreover, CD1a-reactive Tregs were demonstrated to functionally interact with CD1a presenting skin relevant lipids. Ex vivo single cell sequencing of CD1a-reactive Tregs further revealed that upon CD1a stimulation, CD1a-reactive IL-10-secreting effector/memory Tregs from healthy controls and psoriasis patients downregulate Treg lineage and phenotype markers and shift towards a central/memory phenotype. Moreover, gene expression analysis suggests that CD1a-reactive Tregs may present a subpopulation with impaired suppressive capacity.
The second aim of this study was to investigate the therapeutic potential of butyrate and related fatty acids (FAs) to modulate CD1a-reactive T cell activation via alteration of CD1a expression. Here, butyrate and related FAs were demonstrated to partially inhibit expression of group 1 CD1 molecules on monocyte-derived dendritic cells (moDCs) while not affecting general moDC differentiation. CD1a-mediated T cell responses by moDCs were unchanged on treatment with butyrate and related FAs, suggesting that these compounds cannot modulate CD1a expression sufficiently to influence CD1a-mediated T cell responses.
The findings presented in this study demonstrate that Tregs can functionally interact with CD1a and undergo transcriptional and phenotypic re-programming upon CD1a engagement, which in turn may influence skin immunity. While partial modulation of CD1a expression may not be sufficient to alter CD1a-mediated T cell activation, the modulation of CD1a-mediated Treg responses may present a novel therapeutic target for the treatment of skin inflammatory disease.

Advisor: Chen, YL
Ogg, G
Dong, T
Southern African liberation and great power intervention: towards a theory of revolution in an international context

Whether welcomed, feared, or ignored, revolutions have been rare but pivotal disjunctures in the history of the modern world. No history of the states system would be complete without accounting for the transformative impact of revolutions on the security, diplomatic, and economic configurations of the modern international system. Similarly, no political history of most contemporary states would be complete without a discussion of "revolutionary moments" which recast their governments, economies, and societies.
In an attempt to understand revolutions in an international context, this dissertation adopts the method of structured, focus comparison to analyze two cases of revolutionary upheaval -- Angola and Zimbabwe -- within the context of the bi-polar, antagonistic international system. While both Angola and Zimbabwe are located in southern Africa, had agriculturally-based economies dominated by large settler communities, became independent two decades later than most of Africa, gained independence through protracted guerrilla wars, and were not considered vital to either Soviet or American interests, nonetheless Angola experienced a revolutionary socio-economic transformation, but Zimbabwe did not.
To account for this variation, I look for differences in the international context of these two revolutions, specifically changes in foreign policies of the United States and the Soviet Union. I argue that Angola experienced a revolution because both Superpowers engaged in confrontational strategies of supporting and containing revolutionary movements. Zimbabwe did not experience a similar fate because the United States and its allies adopted a cooptive strategy toward the liberation movements, while the Soviet Union again adopted a confrontational strategy.
Drawing from these two cases, I conclude by assessing the influence of cooptive versus confrontational power regarding revolutionary situations in general, and the more universal properties of the dynamic between revolutions and the international system.

Keywords: liberation
Chimurenga War
international
revolutions
great power
revolution
Southern African
great power intervention
Southern Africa
Angola
intervention
United States
Zimbabwe
Advisor: Vincent, J
Investigating the behavioural and neurophysiological underpinnings of a novel bimanual motor learning task

In daily life, we perform many tasks with both hands that require the cooperative and skilled interaction between hands, such as keyboard typing. However, our understanding of the behavioural and neurophysiological underpinnings of how we produce and learn cooperative bimanual skills is sparse.
In this thesis, I addressed this by designing a novel task that measures unimanual as well as different levels of bimanual motor learning. With the novel task, I conducted four independent experiments to answer distinct questions, including characterising learning, and generalisability, as well as understanding learning-related neurophysiological changes using non-invasive brain stimulation and Magnetoencephalography (MEG).
Firstly, I aimed to quantify the learning-related changes of unimanual as well as different levels of bimanual motor learning. Results indicated that the novel task was successfully implemented to characterise learning. Secondly, I investigated if the learning could be modulated with non-invasive brain stimulation using a double-blind sham-controlled study. I replicated the behavioural results of the first experiment, but the applied stimulation did not affect learning the task. Thirdly, I developed different online versions of the task (i.e., training tasks) to measure if this variability across training tasks affected learning and the transfer of learning to multiple transfer tasks. Results indicated that learning depended on the training task, whereas transfer of learning was independent of the training task and depended on the transfer task. Fourthly, I characterised the neural activity of learning the different levels of bimanual interaction with MEG. Results yielded movement-related beta power modulations which were different between the unimanual and bimanual condition. However, they did not differ between the bimanual conditions and did not change with learning.
Taken together, this work provides new insights into how we produce and learn bimanual skills as the task described here allows for a richer description of bimanual interaction. Testing different versions of the task highlights the complex relationship between learning and transfer of learning. Further, this work contributes to our understanding of the neural underpinnings of unimanual and bimanual movements and give directions for future research.

Keywords: transcranial alternating current stimulation
beta activity
magnetoencephalography
brain stimulation
bimanual motor learning
transfer of learning
online experiments
bihemispheric stimulation
unimanual motor learning
Advisor: Stagg, C
Zich, C
Johansen-Berg, H
Fanon's sociogenic approach to antiracist critique

I argue that Frantz Fanon’s sociogenic approach to antiracist critique provides a productive model for political theorists. Rather than treat racism as an ahistorical phenomenon, his analyses of racialization return the problem of ‘race’ to the social. In this respect, I read Fanon as a materialist thinker, one whose immanent critique combines two methodological moments. First, Fanon conducts a genealogical analysis of racial orders, thereby denaturalizing and problematizing the practices, institutions, and discourses that (re)produce them. Second, he adopts an existentialist phenomenology that uncovers the lived experience of racialized subjects. In doing so, he discloses how racial hierarchies can displace both White and Black subjects from ethical relationships to themselves and their actions. I assert that Fanon’s model of antiracist critique improves upon and corrects for the analytical pitfalls that bedevil both normative political theory and critical theory when it comes to ‘race.’ First, political theorists ought to follow Fanon in theorizing racisms as a problem for ideology critique, rather than as either epistemic mistakes or aberrations from egalitarian norms. While racisms do rely on mistaken ideas of hierarchical difference, they are both normal and normative in their contexts of use. Second, Fanon avoids falling back into a crude Manichean ontology that reifies racial categories and disconnects ‘race’ from other forms of social stratification like class or gender. Finally, Fanon provides a more nuanced conception of subject formation under racial oppression than many political and critical theorists do. He doesn’t treat individual agency as an a priori capacity, but instead thinks it as a problematic in its own right. In this respect, I point towards how Fanon’s reworked alienation critique might be productively deployed to understand how persistent exposure to anti-Black racism injures and disempowers Black people in the U.S. today.

Keywords: ideology
antiracist critique
Frantz Fanon
existential phenomenology
critical theory
genealogy
racialization
racial hierarchies
racism
Advisor: McNay, L
Autophagy’s roles in the activation and ageing of CD4+ T cells

Autophagy plays an essential role in the differentiation, homeostasis and renewal of various cell types. Though its molecular machinery has been extensively elucidated, what autophagy specifically degrades remains largely unclear. Here, we created the Lc3b-APEX2 transgenic mouse model based on the proximity biotinylation technique, which, for the first time, enables us to directly map the proteinaceous content of autophagosomes in any primary cell. Through inserting APEX2, an engineered ascorbate peroxidase, into the endogenous LC3B allele, proteins residing in the autophagosomes can be specifically labelled with biotin and easily purified. After the systemic validation of the mouse model, next, I utilised it to explore the molecular mechanism of why CD4+ T cells, which orchestrate both humoral and cytotoxic immune responses, rely on autophagy to expand when facing antigen-stimuli. We discovered the interleukin-7 receptor alpha (IL-7Rα) as one of the autophagosomal candidates in proliferating CD4+ T cells. Mechanistically, we confirmed that excessive surface IL-7R sequestrate the common gamma chain, impairing the IL-2R assembly and downstream signalling crucial for T cell proliferation. Moreover, we investigated how CD4+ T cells from aged mice, which mimic some of the phenotypes of autophagy-deficient CD4+ T cells, also show several unique changes related to cellular ageing. This study provides proof of principle that key autophagy substrates can be reliably identified with this model to help mechanistically unravel autophagy’s contribution to healthy physiology and disease.

Keywords: Cytokine
Aging
T cell
Autophagy
Advisor: Simon, AK
Jostins-Dean, L