The early evolution of small terrestrial bodies: a palaeomagnetic and geochemical study of meteorites

Meteorites act as windows into the early solar system, providing a wealth of information on the composition, formation, and evolution of planetary bodies. After their formation, planetary bodies are reworked by several secondary processes which modify their original chemical and physical properties. In this thesis, I study two such processes (aqueous alteration and impacts), using magnetic and geochemical techniques on stony-iron, iron, and chondritic meteorites. The formation of stony-iron meteorites is a topic of intense research and both mesosiderites and pallasites are hypothesised to have formed through impact mixing of metal and silicates. I use palaeomagnetic and microscopy techniques on the mesosiderite Estherville and show that Estherville does not record a high-coercivity natural remanence. However, Estherville has the ability to record strong (>150 μT) fields. The slow cooling rates recorded by mesosiderites (<1 K/Myr) imply a formation close to the core-mantle boundary, suggesting that they would have been exposed to strong fields if a dynamo was active. However, they do not carry a high coercivity remanence, which may indicate that the mesosiderite-forming impact shut off the dynamo. To investigate the formation of pallasites, I use in situ chemical analysis and find that all metal in Seymchan has the same origin. Based on this result and textural observations, I propose a pallasite formation model involving two or more impacts, and provide additional evidence for the previously proposed link between Main Group pallasites and IIIAB meteorites. Finally, I study aqueous alteration using quantum diamond microscope magnetic mapping to spatially resolve the magnetic signals of the CM chondrite MCY 05231. I suggest that magnetite forms via different reaction pathways in this sample, and that magnetite formed via pseudomorphic replacement of metal leads to the inheritance of magnetic remanence from the precursor grain. I use these results to suggest a magnetic history for MCY 05231, and to discuss implications for bulk magnetic studies of chondrites

Genomic epidemiology and longitudinal sampling of ward wastewater environments and patients reveals complexity of the transmission dynamics of bla KPC -carbapenemase-producing Enterobacterales in a hospital setting

Background: Healthcare-associated wastewater and asymptomatic patient reservoirs colonized by carbapenemase-producing Enterobacterales (CPE) contribute to nosocomial CPE dissemination, but the characteristics and dynamics of this remain unclear. Methods: We systematically sampled wastewater sites (n = 4488 samples; 349 sites) and patients (n = 1247) across six wards over 6–12 months to understand blaKPC-associated CPE (KPC-E) diversity within these reservoirs and transmission in a healthcare setting. Up to five KPC-E-positive isolates per sample were sequenced (Illumina). Recombination-adjusted phylogenies were used to define genetically related strains; assembly and mapping-based approaches were used to characterize antimicrobial resistance genes, insertion sequences (ISs) and Tn4401 types/target site sequences. The accessory genome was evaluated in some of the largest clusters, and those crossing reservoirs. Results: Wastewater site KPC-E-positivity was substantial [101/349 sites (28.9%); 228/5601 (4.1%) patients cultured]. Thirteen KPC-E species and 109 strains were identified using genomics, and 24% of wastewater and 26% of patient KPC-E-positive samples harboured one or more strains. Most diversity was explained by the individual niche, suggesting localized factors are important in selection and spread. Tn4401 + flanking target site sequence diversity was greater in wastewater sites (P < 0.001), which might favour Tn4401-associated transposition/evolution. Shower/bath- and sluice/mop-associated sites were more likely to be KPC-E-positive (adjusted OR = 2.69; 95% CI: 1.44–5.01; P = 0.0019; and adjusted OR = 2.60; 95% CI: 1.04–6.52; P = 0.0410, respectively). Different strains had different blaKPC dissemination dynamics. Conclusions: We identified substantial and diverse KPC-E colonization of wastewater sites and patients in this hospital setting. Reservoir and niche-specific factors (e.g. microbial interactions, selection pressures), and different strains and mobile genetic elements likely affect transmission dynamics. This should be considered in surveillance and control strategies

Causal relevance of different blood pressure traits on risk of cardiovascular diseases: GWAS and Mendelian randomisation in 100,000 Chinese adults

Elevated blood pressure (BP) is major risk factor for cardiovascular diseases (CVD). Genome-wide association studies (GWAS) conducted predominantly in populations of European ancestry have identified >2,000 BP-associated loci, but other ancestries have been less well-studied. We conducted GWAS of systolic, diastolic, pulse, and mean arterial BP in 100,453 Chinese adults. We identified 128 non-overlapping loci associated with one or more BP traits, including 74 newly-reported associations. Despite strong genetic correlations between populations, we identified appreciably higher heritability and larger variant effect sizes in Chinese compared with European or Japanese ancestry populations. Using instruments derived from these GWAS, multivariable Mendelian randomisation demonstrated that BP traits contribute differently to the causal associations of BP with CVD. In particular, only pulse pressure was independently causally associated with carotid plaque. These findings reinforce the need for studies in diverse populations to understand the genetic determinants of BP traits and their roles in disease risk

HtrA-Dependent E-Cadherin Shedding Impairs the Epithelial Barrier Function in Primary Gastric Epithelial Cells and Gastric Organoids

Impaired E-cadherin (Cdh1) functions are closely associated with cellular dedifferentiation, infiltrative tumor growth and metastasis, particularly in gastric cancer. The class-I carcinogen Helicobacter pylori (H. pylori) colonizes gastric epithelial cells and induces Cdh1 shedding, which is primarily mediated by the secreted bacterial protease high temperature requirement A (HtrA). In this study, we used human primary epithelial cell lines derived from gastroids and mucosoids from different healthy donors to investigate HtrA-mediated Cdh1 cleavage and the subsequent impact on bacterial pathogenesis in a non-neoplastic context. We found a severe impairment of Cdh1 functions by HtrA-induced ectodomain cleavage in 2D primary cells and mucosoids. Since mucosoids exhibit an intact apico-basal polarity, we investigated bacterial transmigration across the monolayer, which was partially depolarized by HtrA, as indicated by microscopy, the analyses of the transepithelial electrical resistance (TEER) and colony forming unit (cfu) assays. Finally, we investigated CagA injection and observed efficient CagA translocation and tyrosine phosphorylation in 2D primary cells and, to a lesser extent, similar effects in mucosoids. In summary, HtrA is a crucially important factor promoting the multistep pathogenesis of H. pylori in non-transformed primary gastric epithelial cells and organoid-based epithelial models

A collaborative hackathon to investigate climate change and extreme weather impacts in justice and insurance settings

By bringing together a large group of participants with diverse skillsets, hackathons aim to make good headway into a particular research topic over a short period of time. This collaborative approach supports relationship building, cross team working and the development of technical skills across different areas

The role of morphology in learning to read written words

This thesis investigates morphological processing in reading, examining morphology’s role in linking print to meaning within alphabetic systems. It suggests that developing readers’ systems become increasingly attuned to morphological regularities through accumulated reading experience. The findings underscore that the automatic activation of these structures is crucial in transitioning from novice to expert reader. Additionally, the efficacy of remote online testing for psycholinguistic research is evaluated, a vital aspect given the shifts towards online methodologies. A systematic review (Chapter 2) of 90 studies across Indo-European languages reveals the complexities of morphological processing, influenced by item-specific and reader-specific factors such as structure, frequency, age, grade, and reading ability. This overview sets the stage for the empirical studies that follow. Experiment 1 (Chapter 3) tests the replication of morphological and pseudomorphological priming effects online, confirming that morphological effects are replicable remotely, while pseudomorphological effects are not, likely due to variabilities in online data collection. This outcome highlights the need to select appropriate paradigms for remote testing. Experiments 2 and 3 (Chapter 4) investigate the morpheme interference effect in both adults and adolescents, demonstrating that increased reading skills and greater suffix familiarity significantly enhance the morpheme interference effect, indicating that reading experience facilitates morpho-orthographic decomposition. Experiment 4 (Chapter 5) explores whether induced suffix familiarity can enhance morphological interference, attempting to establish a causal link between suffix experience and morpho-orthographic processing. The findings suggest that one-session exposure is not as effective in enhancing suffix learning as prolonged reading experiences are. Overall, this thesis expands our understanding of morphological processing and its developmental progression during an underexplored period, adolescence. It also offers insights into the methodological considerations of conducting psycholinguistic research remotely

Considerations of growth factor and material use in bone tissue engineering using biodegradable scaffolds in vitro and in vivo

Bone tissue engineering aims to harness materials to develop functional bone tissue to heal ‘critical-sized’ bone defects. This study examined a robust, coated poly(caprolactone) trimethacrylate (PCL-TMA) 3D-printable scaffold designed to augment bone formation. Following optimisation of the coatings, three bioactive coatings were examined, i) elastin-like polypeptide (ELP), ii) poly(ethyl acrylate) (PEA), fibronectin (FN) and bone morphogenetic protein-2 (BMP-2) applied sequentially (PEA/FN/BMP-2) and iii) both ELP and PEA/FN/BMP-2 coatings applied concurrently. The scaffold material was robust and showed biodegradability. The coatings demonstrated a significant (p < 0.05) osteogenic response in vitro in alkaline phosphatase gene upregulation and alkaline phosphatase production. The PCL-TMA scaffold and coatings supported angiogenesis and displayed excellent biocompatibility following evaluation on the chorioallantoic membrane assay. No significant (p < 0.05) heterotopic bone formed on the scaffolds within a murine subcutaneous implantation model, compared to the positive control of BMP-2 loaded collagen sponge following examination by micro-computed tomography or histology. The current studies demonstrate a range of innovative coated scaffold constructs with in vitro efficacy and clearly illustrate the importance of an appropriate in vivo environment to validate in vitro functionality prior to scale up and preclinical application

Human prolyl hydroxylase domain 2 reacts with O 2 and 2-oxoglutarate to enable formation of inactive Fe(III).2OG.hypoxia-inducible-factor α complexes

Hypoxia inducible transcription factors (HIFs) mediate the hypoxic response in metazoans. When sufficient O2 is present, Fe(II)/2-oxoglutarate (2OG)-dependent oxygenases (human PHD1-3) promote HIFα degradation via prolyl-hydroxylation. We report crystallographic, spectroscopic, and biochemical characterization of stable and inactive PHD2.Fe(III).2OG complexes. Aerobic incubation of PHD2 with Fe(II) and 2OG enables formation of PHD2.Fe(III).2OG complexes which bind HIF1-2α to give inactive PHD2.Fe(III).2OG.HIF1-2α complexes. The Fe(III) oxidation state in the inactive complexes was shown by EPR spectroscopy. L-Ascorbate hinders formation of the PHD2.Fe(III).2OG.(+/-HIFα) complexes and slowly regenerates them to give the catalytically active PHD2.Fe(II).2OG complex. Crystallographic comparison of the PHD2.Fe(III).2OG.HIF2α complex with the analogous anaerobic Fe(II) complex reveals near identical structures. Exposure of the anaerobic PHD2.Fe(II).2OG.HIF2α crystals to O2 enables in crystallo hydroxylation. The resulting PHD2.product structure, manifests conformational changes compared to the substrate structures. The results have implications for the role of the PHDs in hypoxia sensing and open new opportunities for inhibition of the PHDs and other 2OG dependent oxygenases by promoting formation of stable Fe(III) complexes

‘Liege lady’: Queen Victoria’s political medievalism

This chapter explores the reception and reader responses to medievalism by women who were engaged in political discussion in the long nineteenth century. From her very accession, Queen Victoria used the nineteenth-century cultural fascination with medieval and chivalric revival to her own political advantage, to manipulate public opinion in favour of her monarchy and her consort, and to explore the social complexities of her own position. Commentators, poets, and artists similarly used medieval settings and imagery to interrogate the anomalies and impossibilities of her role, with the use of the historical figures of King Alfred and Joan of Arc, and the legendary King Arthur, central to these discussions. This chapter will consider women’s reception and political application of medievalism and Anglo-Saxonism in the nineteenth century, from Victoria’s accession to the widespread use of Joan of Arc as an icon for the suffragettes and suffragists in the late nineteenth century. It will explore the political implications of this consistent use of the language, settings, conventions and constrictions of nineteenth-century medievalism throughout Victoria’s reign: from the powerful impotence of the girl-queen’s accession speech, as explored in Elizabeth Barrett Browning’s contemporary poetry; the matron-queen’s casting of her consort as the ideal English knight in portraiture and sculpture, and most obviously in elegiac work after his death. By contrast, suffragists and suffragettes at the end of the century had recourse to medievalism to articulate their struggle for political rights, from the pervasive use of Joan of Arc as the militant woman’s ideal, to the complex historicism of Cicely Hamilton’s A Pageant of Great Women> (1910)