VictorJuiz/thesis huggingface dataset:
Investigating bacteroidetes gliding motility

Bacteroidetes gliding motility is a type of surface motility in which rod-shaped bacteria move up to 2 µm s in a corkscrewing motion. Flavobacterium johnsoniae is the primary model organism for the study of Bacteroidetes gliding. SprB is the main adhesin in this organism and moves in a helix along the cell surface. This movement is guided by an underlying track that is anchored to the inner leaflet of the outer membrane. The essential gliding lipoprotein GldJ, which is helically arranged when visualised in fixed cells, is suggested to form this track. However, direct in vivo imaging of GldJ is yet to be achieved. Two currently outstanding questions about Bacteroidetes gliding motility are 1) how adhesion of SprB to the substratum is controlled so that binding only occurs when moving from the leading to the lagging cell pole and 2) how/if the cell discriminate between the poles. In this thesis, a fusion of the HaloTag domain to SprB enabled labelling of SprB with stable and bright dyes. The movement of SprB could then be visualised using single-particle tracking to reveal the underlying track topology. These tracking data suggest that the underlying track is not a single closed loop currently proposed, but rather a complex and potentially dynamic structure that can form multiple loops and cover most of the cell surface.
SprB is encoded by the sprB operon that further encodes RemFG, Fjoh_0982, and SprCDF. In this thesis I show that all these components, except fjoh_0982, are required for gliding motility but only sprF are required for SprB helical movement. All the sprB operon components required for gliding are also required for SprB-mediated attachment to glass, indicating that they regulate adhesion of SprB. RemG and SprCD move in a helix reminiscent of the SprB movement pattern. The helical movement does not depend on SprF or SprB, but rather on the SprFhomologous N-terminal domain of SprD. Observations of gliding cells with fluorescently labelled SprC revealed accumulation of SprC near the leading cell pole.
This polar accumulation correlated with the direction of movement and was not observed in cells that did not move. Furthermore, a mutant lacking the C-terminal 50 residues of SprD was unable to accumulate SprC at the leading pole. SprB did not show a similar asymmetric distribution in gliding cells. Fluorescence microscopy shows that helically moving sprB operon proteins accumulate at midcell in dividing cells in a GldJ dependent manner. Cross-linking mass spectrometry indicates that GldJ interacts with the sprB operon proteins as well as GldKNO, essential outer membrane components of the type 9 secretion system which is a pre-requisite for Bacteroidetes gliding motility.

Advisor: Berks, B
Online tactical innovation and stagnation: Insights from the aftermath of the Arab spring in Syria and Tunisia 

Digital media has shaped our world in the past decade, empowering people around the globe to express their voices and share ideas. The massive pace of digitisation has also transformed social movements across geo-political boundaries, such as the 2011 Arab Spring, the #MeToo, Hong Kong’s Pro-Democracy, and #BlackLivesMatter movements. Social movements have deployed several innovative online tactics to express their voices; I call these strategies online tactical innovations. In response, counter-movements employed methods of digital repression to target and dismantle social movements. This chess-like game between movements and counter-movements comes with consequences. However, it is hard to find a consensus in social movement scholarship on the precise impact of repression on tactical innovations offline. Thus, the overarching question guiding my research asks: when do social movements innovate online?
I zoom in on the Arab world by examining Syria and Tunisia to understand this action-reaction puzzle. In this thesis, I theorise and contextualise the conditions under which social movements innovate online tactics using a mixed-method approach. Hence, I interviewed 60 digital media experts, bloggers, and activists from Syria and Tunisia from 2019 to 2020. I selected these two case studies because both countries have experienced very different outcomes in their 2011 uprisings. Having generated the original theory of online tactical stagnation, I tested this theory quantitatively using an original dataset pulled out from Google Trends. I was able to conduct a cross-national panel study to examine the structural determinants of online tactical innovations in the Arab world.
By analysing the Syrian and Tunisian cases, I demonstrate that the movements’ ability to introduce online tactical innovations depends on the magnitude of digital repression. On the one hand, I argue that movements adopt new online tactics to overcome digital repression only when digital repression is moderate and bearable. When digital repression is very low or extremely severe, movements are more likely to abandon their new online tactics, a process I refer to as online tactical stagnation. On the other hand, Internet users are more likely to keep employing online tactics on a daily basis despite the changing level of digital repression.
My findings contribute to the larger field of social movement studies in the digital age. By providing a theoretical and practical framework for the study of online tactical innovations, my research advances our understanding of how and when movements employ digital media practices.

Keywords: Social Movements
Tunisia
Arab Spring
Digital Media
Online tactical innovation
Syria
Digital Repression
Advisor: Howard, PN
Authors and aquafortistes: the Goncourt brothers and the nineteenth-century etching revival

This thesis examines the etchings made by Jules and Edmond de Goncourt alongside their writing, placing the Goncourt brothers’ engagement with etching within the historical context of the nineteenth-century etching revival. The brothers made ninety-three etchings from 1859-70, a period that coincides with their major co-written works, including L’Art du XVIIIe siècle, Gavarni, l’homme et l’œuvre and their six novels. The 1860s also marked the height of the etching revival, a movement that forged close connections between artists and writers in order to promote etching as a printmaking medium. Within the revival, the Goncourt brothers provide a unique example of authors who were also etchers, or aquafortistes, and I argue that the brothers’ firsthand experience with etching had an important impact on their writing. Whether as a form of connoisseurship and research for their art-historical work, as a source of thematic and stylistic inspiration for their novels, or as a means for Edmond to mourn and commemorate Jules after his tragic early death, I identify a variety of intersections between writing and etching in the brothers’ œuvre. As a whole, the aims of this thesis are threefold. First, it seeks to reclaim the importance of etching as a source of artistic inspiration for the Goncourt brothers’ writing, building on and extending prior readings of the relationship between literature and art in the Goncourts’ work which have primarily focused on painting. Secondly, it demonstrates how the brothers’ firsthand experience as aquafortistes during the nineteenth-century revival offers a different perspective on etching from the conventional ideas promoted by other writers and critics during the revival. Finally, it aims to expand discussions of the links between literature and art in nineteenth-century France, moving beyond the sphere of painting to reveal important connections between printmaking and writing.

Keywords: prints
French literature
19th century
etching
Advisor: Yee, J
The development of novel artificial intelligence tools for the early detection of cardiovascular disease using computerised tomography

The use of big data approaches in medicine promises to fill technology gaps in the translation of basic biological science into clinically actionable tools for the benefit of patient care. This thesis is focused on the development of necessary clinical cohorts and tools to facilitate the translation of our mechanistic understanding of the role of epicardial adipose tissue (EAT) and the atrial myopathy in adverse cardiovascular disease events. This thesis creates novel risk assessment tools that could facilitate timelier implementation of care for those found to benefit.
Visceral obesity is a driver of cardiovascular disease and has been implicated in multiple leading causes of morbidity and mortality including coronary artery disease, atrial fibrillation (AF) and heart failure. EAT is becoming recognised as a critical regulator of myocardial and vascular biology and serves as a surrogate measure of visceral obesity beyond its anatomical relationship with the heart. The atrial myopathy is closely related to EAT but is the specific disease process that drives the risk of AF and stroke through both myocardial and EAT dysfunction.
This thesis first outlines the development of the largest clinical coronary computed tomography angiography (CCTA) cohort study – The ORFAN Arm 4 Study. This study has now enrolled some 90,000 patients from across eight NHS Trusts to provide the necessary baseline clinical data, CCTA scans, and outcomes data to develop novel automated risk technologies. This thesis conceptualised, developed, and externally validated artificial intelligence powered technologies. These include the automated segmentation and radiomic feature extraction of both the whole heart EAT volume, and the tissues surrounding the left atrium of the heart for the detection of the atrial myopathy. In the largest cohort to date, I show that EAT volume is predictive of key cardiovascular outcomes including myocardial infarction and stroke, but also all-cause and non-cardiac mortality, suggesting that dysfunctional EAT may have far reaching effects beyond the heart. Finally, I demonstrate the successful development and validation of a pilot radiomic risk score for the prediction of ischaemic stroke, laying the foundation for personalised assessment of AF and stroke risk via non-invasive detection of the atrial myopathy.

Keywords: Cardiovascular disease
Artificial intelligence
Computed tomography
Deep Learning
Adipose tissue
Imaging
Advisor: Antoniades, C
Channon, KM
Taste and olfactory representations in the human brain

The aim of this Thesis is to investigate the functional neuroanatomy of taste and olfactory processing in the human brain, including where taste-olfactory convergence is represented and which areas respond to these stimuli as a function of their value as reinforcers. Taste and olfactory representations in the human brain were investigated in five functional Magnetic Resonance Imaging studies. First, we have shown that umami tastants activate similar cortical regions of the human taste system to those activated by a prototypical taste stimulus (glucose) and that the psychophysical enhacement produced by combinations of umami tastants is represented in the orbitofrontal cortex. Second, we found that three pleasant (but not unpleasant) odours activated a medial part of the rostral orbitofrontal cortex and that a correlation was found between the subjective pleasantness ratings of the six odours with activation in this medial region of the orbitofrontal cortex. In contrast, the primary olfactory (but not orbital) cortex was correlated with the intensity ratings. Third, unimodal taste and (both retronasal and orthonasal) olfactory inputs were found to converge into a region of the far anterior, agranular insula, where it adjoins the caudal part of the orbitofrontal cortex. Moreover, the pleasantness of flavour is represented in a medial part of the rostral orbitofrontal cortex. Fourth, the medial orbitofrontal cortex was also activated by intra-venous administration of amphetamine, implying that this region is generally involved in reward processing. Fifth, we have shown that water in the mouth activates the same general areas involved in taste processing including the primary taste cortex, and that the medial orbitofrontal cortex and a part of the mid insula respond to water in the mouth as a function of thirst levels whereas the anterior parts of the insular cortex including taste cortex respond to water independently of thirst levels. These new findings imply that the medial part of the human orbitofrontal cortex is a reward-related area involved in particular in the representation of the reinforcing properties of taste and olfactory stimuli (including water in the mouth) whereas a part of the far anterior, agranular insula and adjoining caudal orbitofrontal cortex encode for the sensory properties of these stimuli, in particular taste-olfactory convergence.

Keywords: smell
tste
orbital cortex
interoception
insular cortex
Advisor: Rolls, E
Electrospun scaffolds to promote tendon tissue regeneration in rotator cuff tears

Improving rotator cuff repair outcomes is an important unmet healthcare need. Rotator cuff tear surgical outcomes have not improved despite the development of advanced biomaterials and surgical techniques in the last few decades. Biomaterials used in repair have generally been adopted from use in other tissues, not tested and developed for the specific needs of human rotator cuff disease.
The aim of this thesis was to investigate biomimetic, synthetic, polydiaxanone electrospun scaffolds specifically in the context of rotator cuff disease. The thesis hypothesises that electrospun scaffolds replicating native fibrous tendon ECM structures will promote tendon fibroblast attachment, proliferation and result in increased matrix deposition. It also hypothesises that biomimicry will induce immune cell responses conducive to tendon healing.
This study reveals important results for the future design and evaluation of biomaterials for tendon and other tissues.
Firstly, polymer and electrospinning parameters were investigated to ensure repeatable, homogenous fibre production. Polydiaxanone supplier, batch and resin storage conditions had significant effects on electrospun fibres. Whilst fibre diameter and alignment could be rescued through electrospinning parameter modification, the different polymer chemistry and altered parameters required to produce scaffolds from degraded resin potentially creates scaffolds with differential biological effects.
Secondly, diseased tendon fibroblasts exhibit significant differences in attachment, proliferation and gene expression when cultured on electrospun fibres compared to healthy tendon fibroblasts. Biomaterial evaluation using fibroblasts from diseased tendon will lead to more applicable results and development of more appropriate treatments.
Thirdly, although the response of tendon fibroblasts to different scaffold configurations was relatively blunted for both healthy and diseased phenotypes, in contrast biomimetic fibre diameters resulted in significant differences in immune cell attachment, which may be advantageous for tissue regeneration.
Finally, adsorbed protein coronas on the scaffold surface can be functionalised to further direct immune cell and to a lesser extent, tendon fibroblast responses.
In conclusion, the relative sensitivity of immune cell populations to biomimetic materials opens a novel immunomodulation strategy for biomaterial augmentation of rotator tendon cuff repair. Future work should explore the relationship between immune cell populations and tendon fibroblasts as a strategy to promote endogenous healing and improved patient outcomes.

Keywords: cell-material interaction
biomaterials
electrospinning
Advisor: Carr, A
Dakin, S
Snelling, S
The role of interferon-gamma-mediated T cell collectivity on CD8+ T cell responses

Immune responses towards intracellular pathogens and tumours rely on CD8+ T lymphocytes, whose function it is to kill infected or cancer cells, while sparing healthy tissue. CD8+ T cell immune responses are characterized by a remarkable degree of poly-clonality and poly-functionality. However, their overall population response is consistent and robust. Much research has focused on individual T cell activation, but how individual, heterogenous T cell responses are integrated at the population-level remains incompletely understood. Upon encountering their cognate antigen in secondary lymphoid organs, CD8+ T cells arrest for prolonged period of times around antigen-presenting cells forming dense cell clusters, which can function as communication hubs enabling T cells to directly communicate with each other and therefore directly modulate each other’s behaviour.
Here we investigated how CD8+ T cells regulate their response through direct T cell-T cell (T-T) communication, with a particular focus on the cytokine interferon-gamma (IFN-γ) and its effect on T cell responses. We found that specific deletion of the IFN-γ receptor on CD8+ T cells results in augmented expansion of antigen-specific effector T cells and in a skewing of the average functional avidity of the T cell repertoire, thus modulating multiple aspects of the response. In addition, we discovered that activating CD8+ T cells preferentially receive IFN-γ from other CD8+ T cells and furthermore that this IFN-γ-mediated communication between T cells is restricted to a specific time window during the activation phase of the response. Finally, we identified a specific CD8+ T cell subpopulation, so-called virtual-memory T cells, to function as the primary source of this early wave of IFN-γ. Altogether, this study highlights an underappreciated facet of the regulatory role of IFN-γ and virtual memory T cells on CD8+ T cell responses against infection.

Keywords: T cell
interferon-gamma
Advisor: Gerard, A
Dustin, M
Host-microbe interactions in inflammation-driven cancer

Colorectal cancer (CRC) is a heterogenous disease of the intestinal epithelium that is characterised by the accumulation of mutations and a dysregulated immune response. A growing body of literature now also illustrates that this is accompanied by an “oncogenic” CRC-associated microbiota, but whether this dysbiosis is a functional hallmark of CRC or merely a bystander effect of disease is unclear. Therefore, the aim of this DPhil project was to identify changes within the microbiome during cancer progression and the functional consequences. To achieve this, we induced dysbiosis in genetically susceptible mice by colonisation with the pathobiont Helicobacter hepaticus (Hh) followed by the treatment with the carcinogen azoxymethane (HhAOM).
Using a range of unbiased longitudinal approaches, we found a distal colon-specific neutrophil signature during tumorigenesis and identified 118 genes that were differentially expressed in HhAOM versus control mice, indicative of putative tumour-promoting properties. Amongst these, the enzyme peptidyl arginine deaminase 4 (PAD4) was upregulated in epithelial cells of early and late tumorigenesis. PAD4 was verified to play a functional role in cancer progression because therapeutic in vivo inhibition reduced tumour area. Alongside this observation, we discovered that Hh resides within established tumours but lacks the capability to drive CAC in gnotobiotic settings.
Collectively, our findings suggest that Hh-driven colitis triggers an early neutrophil influx into the distal colon which fosters a microenvironment that promotes tumour progression characterised by the expression of PAD4. These observations open new potential avenues to explore tumour-promoting function of neutrophil subsets in more detail and the role of the citrullination enzymes like PAD4 in CRC progression.

Keywords: neutrophils
immune system
microbiome
helicobacter hepaticus
inflammation
colorectal cancer
pepetidyl arginine deaminase
Advisor: Powrie, F
Mann, E
Constitutions

This collection consists of a series of texts and documentation of artworks that attend to modes of constituting social bodies. A constitution might allude to a map, a garment, a code, cosmogony, a body, a people, an agreement, or an enfolding process. These texts and works move the social through bodies—biological, political, infrastructural, and digital—and relate such bodies’ knowledge in various states of digest: partiality, fluidity, congelation, breakdown. They are reflections on consuming, ingesting, and metabolizing, or in other words, processes of incorporating and embodying. They are reflections on ways of moving through time and space. Somatic metaphors can include physical movement as well as how other entities move between bodies, like pathogens, or knowledge. Circulations lead us from inside out, modeling larger phenomena and technologies on bodily networks. Such networks might be reassimilated into bodies, as codes might likewise be embodied.
To be a body amongst others is a process of forming via transmission, to acknowledge that a body is an unstable assembly-in-process, a series of constitutions.

Keywords: social forms
technology
infrastructure
body
art
Advisor: Martin, D
Bull, M
Design of multivalent DNA nanomaterials for use in cancer diagnostics and therapeutics

Cancer is one of the major causes of mortality nowadays, owing to the lack of accurate diagnostic and therapeutic techniques. DNA-based nanomaterials show extraordinary performance in cancer diagnosis and have applications in therapy, owing to their predictable secondary structures, small sizes, excellent biocompatibility, and programmability.
Rolling circle amplification (RCA) has been identified as a promising technique to make DNA nanomaterials, including DNA hydrogels, origami, nanoribbons, nano scaffolds and DNA nanoflowers (DNFs). These DNA nanomaterials have potential in a wide variety of applications, involving drug delivery, in vivo imaging, electronic circuit fabrication and therapeutics. However, there was a lack of chemistry to expand their functionality, which greatly limited their applications. To address this, we developed a strategy involving commercially available modified nucleoside triphosphates in RCA, resulting in densely modified products. The modified RCA products can then be functionalised by targeting moieties such as aptamer and peptide, which enhance their binding ability towards specific cancer cells.
The size of the RCA generated particles can be tuned through reaction time, Mg2+ concentration and the addition of polymers such as PLL and PEG. The PEGylated products can be labelled using the abovementioned method, leading to condensed fluorescent particles with better cellular uptake.
Additionally, a nanocarrier system based on cyclic DNA was designed and evaluated for mRNA detection in cells. The untemplated cyclisation of DNA through CuAAC chemistry was efficient, and the multivalent system showed an improved binding towards target cancer cells. However, the internalisation of the system by cells needs to be improved. Entrapment of the system in subcellular compartments was observed, which significantly increased the background signal.

Keywords: DNA aptamer
cancer diagnostics
mRNA detection
DNA nanostructure
DNA nanoflowers
Advisor: Brown, T