VictorJuiz/thesis huggingface dataset:
The deubiquitylase TRABID coordinates sex-specific neurodegeneration in drosophila melanogaster
Keywords: immunity
neurodegeneration
sex dimorphism
drosophila
ubiquitylation

Ubiquitin-related post translation modification (PTM) plays an important role in cellular signalling. TRABID is a deubiquitylase that preferentially hydrolyses Lys29 and 33 ubiquitin chains and is known to affect inflammation and consequently, neurodegeneration as the latter is considered functionally linked to the former. However, sex differences are widely observed in both inflammation as well as neurodegeneration phenotypes. In this study, I investigated sex dimorphism, in ubiquitination at the intersection of inflammation and neurodegeneration. I demonstrated Drosophila TRABID has similar enzymatic activity as human TRABID and generated an enzymatically inactive TRABID (trbdC518A) in Drosophila flies. I discovered that trbdC518A has a sexually dimorphic impact in the insect’s locomotor activity, sleep pattern, lifespan, cerebral cells count, brain volume and NF-κB signalling. When blocking female development in astrocytes or immunocompetent cells, sex dimorphisms in locomotor activity and NF-κB signalling are partially eliminated. Further evidence ubiquitinomics and proteomics of fly heads, provided insight into the sex-specific impact of trbdC518A.
Designing Church of England churches between the wars: process and participation
Keywords: architecture
London
church
Manchester
liturgical reform
twentieth-century
interwar
suburbs

In the Interwar period, the Church of England built a great number of churches to serve the expanding urban suburbs. Yet, despite their proliferation, this thesis is the first to explore the contribution of these stylistically eclectic buildings to the arc of twentieth century architectural history. Contradicting the post-war Liturgical Reform Movement narrative, this thesis argues that these churches form a key part of the design timeline of the century, presenting evidence of evolutionary changes previously overlooked due to the noise of many competing opinions and the lack of a generally accepted philosophy. Focussing on the Dioceses of London and Manchester, this study demonstrates that understanding the process of design, and within that the roles played by three key groups, the Church, the people, and the architects, is vital to interpreting these buildings.
The motivation, influence, and prejudices of each of these groups as design instigators are interrogated in the first four chapters. Liturgical change and experiments are identified as factors influencing design, and the important role of the newly created Parochial Church Councils as participants in the process is established. The architects’ views are investigated, in roles as commissioned designers and as gatekeepers on advisory committees. Architects seeking to maintain traditional approaches to church design and those intent on modernising through collaboration with clients and evolving a stylistic ‘middle way’ are contrasted. Chapters five and six examine the physical attributes of the buildings: externally displaying manifestations of the contradictory aspirations of suburbia and site practicalities, and internally as evolutionary experiments in accommodating new liturgical emphases. Concluding with an application of the findings to the claims of post-war polemicists, the eclecticism of these churches is re-cast - no longer an indicator of a moribund era in church design, but instead evidence of experimentation, imagination, and adaptation within prevailing norms.
Development of a model system for studying crustacean immunity
Keywords: vibrio bacteria
transcriptome
infection
innate immunity
crustacean

Our current understanding of crustacean immunity lacks sufficient scope because it mainly comes from research on insects and decapods. Little is known specifically about the immunity of amphipods, which constitutes a large proportion of crustacean species. The goal of my thesis is to develop a model system for studying crustacean immunity using the amphipod Parhyale hawaiensis, which is an emerging animal model in many research areas. P. hawaiensis was challenged with Vibrio bacteria to elicit an immune response. P. hawaiensis was resistant to Vibrio bacteria under normal conditions but injury significantly increased mortality rate due to increased bacteria entry. Whole-body transcriptomic response after 24h bacterial challenge yielded hundreds of differentially expressed genes. Additional in vivo bacteria, qPCR, and RNA-seq measurements across the infection time course provided a comprehensive overview the immune system after bacterial challenge. The expression pattern of Relish closely matched that of in vivo bacteria. Key effector genes (i.e., TEP, ALFs, and crustin) upregulation was critical in determining survival. At 4h, upregulation involved pathogen recognition receptors and Toll/IMD pathway components. At 8h, immune regulation and effector activities peaked with the aid of JAK-STAT pathway components. At 24h, peak bacterial load pushed the immune system to the limit. Immune system returned to near normal at 168h. Based on in vivo bacterial measurements and stronger transcriptomic response, females seemed to exhibit higher immunocompetence. Only some immune related genes (e.g., IMD and JAK-STAT pathway components) were differentially expressed in both sexes. Toll pathway components were only differentially expressed in females. Hemocytes imaged using imaging flow cytometry were divided into five subpopulations based on size and granularity. The size of larger hemocytes increased by 9.3% after bacterial challenge and these cells may be involved in antioxidant defense and phagocytosis bacterial clearance based on orthologs. The hemocytic transcriptome was very distinct from whole animal and hemocytic response to bacteria was much stronger with 2077 upregulated and 1599 downregulated genes. Key immune genes (e.g., scavenger B, GNBPs, and Tollip) with hemocytic pathogen recognition functions in other taxa were identified. Findings from my thesis better our understanding of the understudied amphipod immunity and provide additional insight into the immune system of the phylogenetically close decapods.
Development of computational tools for variant calling in single-cell RNAseq
Keywords: single cell rnaseq single-cell barretts mutagenesis variant calling mutations sequencing cancer bioinformatics

Single-cell sequencing technologies have unsurprisingly become a favourable choice for studying key biological questions about cell heterogeneity, rare cell types or lineages. It is only cell-level resolution that allows for an accurate analysis of internal cell processes such as mutagenesis. Eventually, single-cell RNAseq could provide an explanation of mechanisms that lead to the ultimate transformation of healthy tissues into cancerous lesions. One of the main interests of my lab is Barrett’s oesophagus. It is a highly clonal disease and a likely cancer precursor. We decided to take advantage of the single-cell RNAseq technology in order to attempt to identify the tissue of origin of the disease which, despite years of research, still remains unknown. However, the range of methods for identification of mutations in single cells is very limited. In order to address that, we developed our own single-cell RNAseq variant caller. We validated it on a publicly available breast cancer dataset by achieving a reasonable intersection of our results with the output of commonly used bulk tools. Furthermore, we showed that our caller was capable of identifying expected data characteristics such as known breast cancer signatures and mutations in breast cancer genes. We then applied our method to the Barrett’s dataset to investigate connections of Barrett’s with surrounding tissues. Contrary to the previous transcriptomic analysis conducted on the same dataset and indicating a Barrett’s-oesophagus connection, our results revealed a more likely link of Barrett’s with the stomach.
'Bloodsuckers of the Commonwealth': anti-monopoly petitioning in late Elizabethan and Jacobean England (c. 1590-1625)
Keywords: petitioning
Elizabeth I
public sphere
monopolies
livery companies
James VI and I

In the late Elizabethan and Jacobean period, monopolies emerged as a crucial tool of crown financial policy. In response, subjects petitioned crown, council, and parliament to lament the changes these grants wrought on their trades and livelihoods. This thesis will offer an analysis of anti-monopoly petitioning activity between 1590-1625. It will demonstrate the vibrancy and sophistication of petitioning in this often-overlooked period, whilst illuminating the important intersection between politics and economics at the turn of the seventeenth century. This economic issue politicised subjects, who turned to petitioning to lament the effects of this intrusive form of prerogative finance. They embraced the opportunities to approach parliament, council, monarch, and even new commissions charged with managing economic petitions. Subjects proved willing to draw on wider discourses in political culture and economic thought as bargaining strategies within petitions designed to further their own economic interests.
This thesis will adopt a case study approach, focusing on the monopolisation of leather, starch, glass, and cloth. It will draw on a range of sources, predominantly manuscript, from such archives as the State Papers and individual livery companies. The role of London’s livery and overseas trading companies both as petitioners, and as a source of concerted opposition themselves, will be explored throughout. In addition, the capacity for subjects to organise petitioning activity independently of the auspices of corporate organisation will be shown. By analysing often overlooked petitioning campaigns, the complex alliances between courtiers and artisans made possible in this era of monopolisation will also be illuminated. Through a focus on these anti-monopoly petitioning campaigns, this thesis will add to understandings of manuscript petitioning culture in the late Elizabethan and Jacobean periods, whilst demonstrating the importance of economic issues to the politics of the early modern public sphere.
Elucidating the neural correlates of cost-benefit decisions in a rat cortico-basal ganglia network

Keywords: frontal cortex
basal ganglia
motivation
single-unit electrophysiology
cost-benefit decision-making
value-guided behaviour

Adaptive value-guided decision-making often requires weighing-up of costs and benefits of pursuing an available opportunity. Several brain areas, particularly in frontal- striatal circuits, have been reported to be important for this behaviour. However, little is currently known regarding how the decision variables are represented and evolve on the single cell and population levels across these circuits within the confines of a single behavioural paradigm. We developed a novel rodent cost-benefit “accept-reject” task, in which food-restricted rats choose whether or not to run to the end of a corridor to collect sucrose pellets based on the prospective reward (4 different levels, varied trial- by-trial, signalled by auditory cues) and effort cost (3 different levels, varied over blocks of trials, implemented with barriers placed in the corridor that needed to be scaled to reach the reward magazine). Behavioural data (n=12 rats, average 1119 trials per animal) demonstrate a positive effect of reward and a negative influence of effort on the likelihood of accepting an offer, without an interaction between the two. Outcome devaluation strongly reduces acceptance of any offer. A subset of rats (n=5) were also implanted with a bespoke driveable micro-electrode array targeting, anterior cingulate cortex (ACC), medial orbitofrontal cortex (mOFC), dorsomedial striatum (DMS), ventral pallidum (VP), and subthalamic area (STA) and electrophysiological recordings were collected as they performed the task. Analysis of spiking data (n=4 rats; average 119 cells per region per animal) suggests that individual neurons in the 3 targeted basal ganglia areas (DMS, VP and STA) encode reward and/or, to a lesser extent, effort with high fidelity during cue presentation, while neurons in the two cortical areas (ACC and mOFC) display weaker tuning to reward/effort across multiple task points. By contrast, decision is progressively signalled by mOFC, DMS and VP units after action initiation. Decoding analyses using all the units from individual areas in a given session (ensembles) revealed that reward is signalled with similar spatial and temporal characteristics to single units. By contrast, effort is represented by DMS ensembles in a time-distributed manner and is dependent on diverse underlying neuronal activity profiles. These results are consistent with a parallel and distributed system for processing cost-benefit decision variables in the frontal cortical-basal ganglia network.
The ecology and ecosystem services of insectivorous bats in rice dominated landscapes
Keywords: ecosystem services
landscape ecology
rice agriculture
bat behaviour
acoustic analysis
pest control

Agriculture is a vital artery of the Indian economy, and supports more than half the population. Rice is a key crop of agriculture in the country, but sees consistent loss of yield to insect pests. Successive measures to stem this loss have not had a significant effect and with climate change threatening to further exacerbate the issue, developing biological methods to control pest insects is of prime importance.
This thesis proposes bats – top predators in the rice ecosystem – as a partial solution to the problem of insect pests. The studies detailed within describe bat behaviour in the context of the rice ecosystem from three angles. The first is how the changing conditions of a rice growing season affect the activity of bats. The second is identifying features in the landscape surrounding a rice field that influence bat activity, and the scales at which they are most influential. This would indicate the best design of an agricultural landscape to maximise pest control effect of insectivorous bats. The third is to experimentally test the value added to the rice crop by bats, and the effect that their removal or loss would have on the health and yield of the crop.
By considering one system from these three perspectives, this thesis not only assesses the value of insectivorous bats to rice, but also explores how this value may be bolstered for the benefit of bats and the agricultural industry together.
Set in rice-dominated landscapes of Assam, India, this thesis reports that bats are influenced by insect activity in rice fields, nightly temperature, and moonlight intensity. It also reports that landscape features related to tree cover, such as area of forest within 1km, distance to edge, and distance to forest, as well as urban landcover, all influence the activity levels of bats in rice fields. It also shows finally that when bats are prevented from hunting over crops, it results in a decrease in plant health.
Accompanying these results are more fundamental descriptions of bat morphology and acoustic characteristics from Assam, where such data are scarce, as well as data on the diet of bats active around rice fields. These data have not yet been analysed due to COVID complications, but in due course will add yet another dimension to the system under focus, and increase the resolution with which targeted interventions can be made.
Spin dynamics of radical pairs in magnetic fields
Keywords: magnetic field effects
spin dynamics

The remarkable ability of migratory birds to use the geomagnetic field for their navigation has been fascinating scientists for more than 50 years. Extensive studies, from experiments to theories, suggest that avian magnetoreception may arise from photo-induced radical-pair reactions in the birds’ eyes. Although the energy for the interaction of a single molecule with a magnetic field as weak as ∼50 μT is more than a million times smaller than the thermal energy, such weak fields can still significantly influence spin-selective reactions via the modulation of radical-pair spin dynamics.
A navigational cue requires the radical-pair magnetoreceptor to be sensitive to the direction of an external magnetic field. In Chapter 3, I explore the anisotropic weak magnetic field effect on the eigenstructure and the spin dynamics of a model radical pair with respect to the field direction. Then, the feasibility of the “reference-probe” model for radical-pair magnetoreception is studied.
Birds’ disorientation in a static magnetic field caused by extremely weak radiofrequency fields is considered to originate in magnetic effects on the sensory molecules, though it is not yet understood exactly in quantitative detail. A more convincing test - reorientation rather than disorientation in a radiofrequency field in the absence of a static magnetic field - is proposed in Chapter 4. Elaborate theoretical study of the resonance effect induced by a radiofrequency field is followed by spin dynamics simulations for flavin-based radical pairs to evaluate the possibility of a “radiofrequency compass”.
The “B1/2” value, a parameter that characterises the magnetic field-dependence of the reactions, was found to be larger than expected on the basis of the hyperfine interactions and to have significant time dependence. This behaviour is considered as a strong indication of spin relaxation. In Chapter 5, I present several possible candidate spin relaxation mechanisms and find the specific one, singlet-triplet dephasing (STD), that could account for the time-dependent magnetic field effect. In cryptochromes, the only candidate magnetoreceptor, STD probably originates in the electron hopping between tryptophans. Furthermore, simulation shows that STD, even quicker than chemical reactions, does not seem to destroy the directional sensitivity of the FAD-Trp radical pair to weak magnetic fields.
Chiral molecules could act as spin filters that preferentially transmit electrons with spins polarized parallel or antiparallel to their direction of motion. This chiral-induced spin selectivity (CISS), as a spin polarization effect that could be observable by electron paramagnetic resonance (EPR) experiments, is included in the radical pair mechanism in Chapter 6. CISS effects offer the possibility of evolving a more sensitive or precise compass. The associated lack of field- inversion symmetry potentially explains the observation of a polar magnetic compass response.
A world from nowhere: nineteenth-century expert politics and the technocratic international
Keywords: Suez canal
international telegraph union
world's fairs
expertise
technocracy

The long nineteenth century witnessed both the entrance of “international” into the modern political vocabulary, and the rise of expert-centred international practices and institutions. Historians of international relations have thus far not investigated the connection between these two developments. This thesis engages the topic by asking: how should we make sense of this coevolution? It conceptualises the simultaneous emergence of internationality and expert politics as a case of domain differentiation: the articulation of the distinctiveness of a sphere of political action as a mode of authorisation. Multiple such articulations coexist and potentially conflict—domain differentiation is messy, inchoate, and contested.
Yet rather than advance a causal-predictive claim about why experts emerged as central actors of international order, the thesis examines the indeterminate processes by which people with projects constructed a technocratic international with authorising effects. It adds a methodological argument for studying differentiators. Combining intellectual history with historical sociology, the thesis shows how by the mid-nineteenth century new elite actors were elevated to technical expert status to gain international authority. To do so, they articulated the international as a domain of impartiality, where scientific and technical experts should have special authority. This claim also was an attempt to shield their projects from political capture and contestation. A technocratic worldview gave them the confidence to first undertake large-scale engineering works across borders, and then worry about implications, from extraterritoriality to dispossession and informal empire, later. This double move—grasp for authority and deflection of contestation—was the chief innovation of the “world from nowhere.”
This was, as case studies based on archival research show, naturalised at the first World Fairs in London and Paris; it was used to justify the making of the Suez canal and its attendant extraterritorial ‘international zone’; and it spurred on the cable industry at the 1865 International Telegraph Conference. Saint-Simonians, industrial capitalists, and free-trade liberals all contributed to this endeavour. But this was not a triumphant history. For all their professed hopes for an expert-driven engine of peace, they ended up facilitating and providing the infrastructure for what they had sought to overcome: military-territorial power politics, aggressive nationalism, and renewed imperial expansion. Given its influence on modern international organisations, excavating this link between expert-driven impartiality and technocratic international interventions puts difficult questions about the legitimacy of international institutions into perspective.
Melanin nanoparticles as a potential iron chelation therapy for women with beta thalassemia during pregnancy
Keywords: maternal-fetal interface
melanin nanoparticles
placenta
medication in pregnancy
iron overload
perfusion
MFM
thalassemia
iron chelation

The main challenges in developing medications that are safe to use during pregnancy is to minimize foetal exposure to the drug, which has become increasingly challenging with the increased prevalence of chronic conditions among young women. In beta thalassemia, patients can now survive beyond puberty and achieve pregnancy. β-TM pregnancies, however, are at high risk of maternal morbidity due to the complication of iron overload. Current chelation medications are withheld during pregnancy as they can cross the placenta causing potential risk to the foetus. This thesis addressed this complicated challenge in which a chelation agent needs to be retained in the maternal circulation and not cross the placenta. Previous experiments in iron-overloaded mice have shown that melanin nanoparticles can effectively chelate iron. Since the interaction between nanoparticles and cells/tissues is determined by particle characteristics and functionalization that can manipulated at synthesis, it was hypothesized that a melanin nanoparticulates with appropriate characteristics could be restricted from movement across the placenta, and safely used to treat the mother. A library of melanin nanoparticles of different sizes was established, and functionalized. This was followed by particle characterization and imaging. Functional analysis confirmed that particles were able to chelate iron more effectively than the iron chelator desferroxamine at the same concentration. Haemocompatibility testing found that the particles did not cause red cell haemolysis or blood clots. Moreover, it was determined that a cut off size of 200 nm can be restricted from passing across the placental barrier in an in vitro model using a human choriocarcinoma cell line and ex vivo human placental perfusion. Finally, physiological changes during pregnancy such as the decrease in plasma albumin concentrations can alter the volume of distribution as well as the transport of drugs. Proteomics analysis was used to identify nanoparticle binding proteins in the serum from pregnant women, non-pregnant women, and women with beta thalassemia. 43 significantly different proteins between the three serum groups were identified, followed by the gene ontology analysis of cellular components that revealed the mediation of biological identity of the bio-inspired melanin in the biological system.