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The Molecular Biomarkers of Sperm Fitness
Get PDFSperm are among the most specialised and variable cell types in the animal body, differing not only across species but also between and within individuals. This molecular and phenotypic diversity has important implications for fertility, yet the mechanisms generating variation among sperm and their evolutionary and clinical consequences remain poorly understood. This thesis combines quantitative proteomics, bioinformatics, and single-cell analysis to investigate how environmental and physiological stress shape sperm phenotype and to test whether molecular heterogeneity within ejaculates provides a substrate for haploid selection. In Chapter 1, tandem mass tag proteomics revealed that acute heat stress in zebrafish (Danio rerio) testes induces a coordinated shift in the proteome, with depletion of proteins linked to spermatogenesis and motility and enrichment of chaperones and stress-response factors, demonstrating dynamic germline remodelling under environmental challenge. Chapter 2 presents a comprehensive zebrafish sperm proteome that establishes a baseline for functional and comparative work and shows that stress-induced testicular changes translate into altered sperm protein composition. In Chapter 3, fractionation of human ejaculates by swim-up and methyl-cellulose migration revealed consistent proteomic differences between higher- and lower-fitness sperm subpopulations, identifying candidate surface biomarkers of sperm quality. Chapter 4 validated two of these candidates, OLFM4 and CTNG, as accessible on the sperm surface and inversely associated with sperm longevity using spectral imaging flow cytometry. Together, these studies demonstrate that sperm phenotypes reflect underlying molecular differences that can be detected, quantified, and linked to fitness-related traits. They provide molecular evidence for haploid selection acting within ejaculates and establish a translational foundation for biomarker-based sperm assessment in assisted reproduction
Assessing the impact of Active and Assisted Living technologies on older adults’ psychosocial well-being: there is room for improvement
No full textPopulation aging is a global phenomenon. In developed countries, active and assisted living (AAL) technologies have shown potential to enable older people to lead healthy and independent lives. However, the literature lacks an integrated assessment of AAL technologies that also takes into account their effects on subjective psychosocial well-being. As part of the RAISE project (Robotics and AI for Socio-economic Empowerment, PNRR, Mission 4 Education and Research, Innovation Ecosystem for the Liguria Region), a systematic review of the evidence on the effect of AAL technologies on the psychosocial well-being of older people is under way, and has selected eleven articles. This paper intends to discuss the critical methodological aspects of these articles in order to provide recommendations for conducting more robust research in this area
Harnessing the Gut Commensal Bifidobacterium spp. to Modulate Anti-Tumour Immune Responses
No full textThe gut microbiome plays a critical role in shaping host immunity, and specific commensal bacteria, including Bifidobacterium, have been implicated in modulating anti-tumour immune responses. However, the immunoregulatory properties of bacteria are highly strain-specific, and systematic methods for identifying therapeutic strains are lacking. This thesis aimed to develop a functional screening pipeline to characterise immunomodulatory activity across diverse Bifidobacterium isolates and to evaluate selected strains in murine cancer models.
A multi-tiered in vitro and ex vivo screening platform was established, incorporating THP-1 monocyte NF-κB activation assays, dendritic cell cytokine profiling, DCCD8+ T cell cocultures, and human PBMC immune phenotyping. Screening of >150 Bifidobacterium isolates from both human and animal gastrointestinal sources revealed substantial heterogeneity in their ability to stimulate innate and adaptive immune populations, enabling prioritisation of candidate strains for in vivo study.
In a luminal A-like breast cancer model, selected B. bifidum strains significantly reduced tumour growth and were associated with enrichment of cDC1 in tumour-draining lymph nodes, increased costimulatory molecule expression on dendritic cells, and enhanced CD8+ T cell effector responses. In an orthotopic pancreatic ductal adenocarcinoma model, distinct strains exerted divergent effects on tumour progression, with several strains markedly reducing hepatic metastatic burden in the absence of consistent primary tumour control, consistent with systemic immune modulation.
Collectively, these findings demonstrate that Bifidobacterium strains exhibit distinct, strain-dependent immunomodulatory profiles with divergent effects on tumour immunity. By integrating high-throughput functional screening with in vivo validation across multiple cancer models, this thesis establishes a coherent framework for linking strain-level immunomodulatory heterogeneity to anti-tumour immune outcomes, underscoring the importance of strain-level resolution in microbiome-based cancer research
POS0704 Lipidomics and inflammation following disease onset in newly diagnosed rheumatoid arthritis: insights from the DESIGNA (Dietary Signatures in Arthritis) study.
No full textBackground: Rheumatoid arthritis (RA) is the most common autoimmune inflammatory arthritis, with a UK prevalence of 0.8% in 2022/23 estimates. RA causes chronic systemic inflammation of synovial joints, and can result in joint destruction and significant disability. Metabolomics facilitates the profiling and understanding of metabolites (an intermediate or end-product of metabolism) and provides insights into disease mechanisms and potential therapeutic targets. Objectives: This study aimed to investigate the association of serum free fatty acid (FFA) metabolites with inflammation, measured by the disease activity score (DAS28) in a cohort of newly diagnosed patients followed over 7 years after their disease onset. Methods: A total of 94 RA patients from the NOAR and Norfolk EPIC cohorts were included in the Dietary Signatures in Arthritis (DESIGNA) study. All patients had stored blood samples analysed for fatty acid metabolites in serum from their baseline (newly diagnosed) sample and one follow-up time (2, 3, 5 or 7 years post diagnosis). Eleven long-chain free fatty acids (FFAs) and eight short-chain fatty acids (SCFAs) were isolated from serum samples using well established liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques which resulted in absolute concentrations (uM) of metabolite being measured. Multilevel modelling was employed to assess the relationship between fatty acid concentrations and DAS28, adjusting for age at RA onset, gender, BMI, and time since diagnosis. A multiple testing correction was applied, with significance defined as p < 0.05. Results: Eighty-four patients were analysed after excluding 10 with missing DAS28 scores. A summary of the output from the multilevel models is shown in Figure 1. Higher levels of the SCFAs propionic acid and butyric acid were significantly associated with lower DAS28 scores (p < 0.005) indicating a possible anti-inflammatory role. Conversely, higher levels of the long-chain FFA arachidonic acid (ARA) were associated with higher DAS28 scores (p < 0.01), consistent with the known pro-inflammatory role of ARA. Age at onset, gender and BMI were not significantly associated with DAS28 scores. DAS28 decreased significantly over time (P<0.05)
Developing an Understanding-Oriented Epistemology for the Environment
Get PDFAn understanding of the natural environment and present environmental challenges involves a vast amount of complex information. This produces significant epistemic difficulties that epistemology should have something to say about. This thesis makes three important points about an adequate epistemology for the environment. First, a focus on propositional knowledge is not sufficient to make progress on the epistemological questions that arise from our relationship to the environment, so we should shift our attention to the epistemic state of understanding. Second, we should take interest in what character traits make a person a virtuous environmental thinker. I argue for understanding-oriented accounts of some environmental-epistemic virtues: ‘big picture thinking’ virtues, like outward-lookingness, and the virtue of honesty. Third, I contend that epistemologists should refer to empirical research and engage in interdisciplinary approaches to explore how epistemic difficulties are experienced in relation to actual environmental interventions. I carry out a case study on the Nearshore Trawling Byelaw (conservation management in Sussex that bans harmful fishing practice) to illustrate the point. I review relevant documents and use semi-structured interviews to understand how epistemic successes and difficulties were experienced in practice
Olfactory implants: international opinion paper on emerging technologies and clinical applications
No full textWriting the Detectives:Character and the Series Form
No full textCrime fiction first emerged in the Victorian era and its series form continues to dominate the genre. Despite the prevalence of crime series, very little research has been done on how character is conceived. The Element’s focus is contemporary, from the 1970s onward, and it determines the literary theory and conventions behind writing the detectives in these modern meganarratives. Exemplary series and a range of subgenres are analysed, thriller to cosy crime, professional investigator to amateur sleuth, embracing diversity and different gender identities. Previous examinations have tended to interpret the detective figure as either mythic or realist, but the author argues that both modes are combined in the contemporary crime series, generating a mythorealist protagonist. This creative-critical Element celebrates the vibrancy of the form and its capacity to investigate the human condition. It also considers future trends and concludes with the author’s own guide to writing a crime fiction series
Essays on Inequality, Fairness and Cooperation
Get PDFThis thesis explores how individuals perceive inequality, fairness and coordination in strategic and non-strategic environments using experimental economics. Across three studies, it examines whether redistribution preferences depend on procedural fairness and the source of inequality, and how individuals coordinate in environments where outcomes hinge on shared expectations.
The first study investigates the role of procedural fairness by testing whether redistribution preferences differ when inequalities arise from unequal opportunities. Using a novel experimental framework inspired by Sugden and Wang (2020), participants engaged in a card game with equal or unequal opportunities before making redistribution decisions. Results indicate that redistribution choices were largely unaffected by equality of opportunity, suggesting that participants prioritise outcomes over processes when evaluating fairness.
The second study extends this inquiry by examining the effects of strategic choice and strategic luck on redistribution. Unlike prior work that focuses on non-strategic settings and random lotteries, this experiment situates inequality within a strategic coordination game, where incomes depend on both individual and others’ decisions. Comparing redistribution under strategic and non-strategic conditions, the findings reveal that initial income distributions exert stronger influence than (strategic and non-strategic) choice versus luck as the source of inequality itself.
The third study shifts focus to coordination behaviour in pure coordination games, addressing why players successfully align choices when labels are present. In a 30-round experiment using labels from diverse categories, participants achieved coordination rates above chance. While online frequency measures (website rankings and Google search rankings) did not predict success, label frequency in books significantly enhanced coordination, highlighting the role of cultural salience in shaping focal points.
Together, these studies contribute to the literature on inequality, fairness and coordination by showing that individuals often emphasise distributive outcomes over procedural considerations, that the initial distributions of incomes outweighs luck versus choice as the origins of inequality, and that cultural salience underpins coordination success
Characterizing semi-directed phylogenetic networks and their multi-rootable variants
No full textIn evolutionary biology, phylogenetic networks are graphs that provide a flexible framework for representing complex evolutionary histories that involve reticulate evolutionary events. Recently phylogenetic studies have started to focus on a special class of such networks called {\em semi-directed networks}. These graphs are defined as mixed graphs that can be obtained by de-orienting some of the arcs in some {\em rooted phylogenetic network}, that is, a directed acyclic graph whose leaves correspond to a collection of species and that has a single source or root vertex. However, this definition of semi-directed networks is implicit in nature since it is not clear when a mixed-graph enjoys this property or not. In this paper, we introduce novel, explicit mathematical characterizations of semi-directed networks, and also multi-semi-directed networks, that is mixed graphs that can be obtained from directed phylogenetic networks that may have more than one root. In addition, through extending foundational tools from the theory of rooted networks into the semi-directed setting — such as cherry picking sequences, omnians, and path partitions — we characterize when a (multi-)semi-directed network can be obtained by de-orienting some rooted network that is contained in one of the well-known classes of tree-child, orchard, tree-based or forest-based networks. These results address structural aspects of (multi-)semi-directed networks and pave the way to improved theoretical and computational analyses of such networks, for example, within the development of algebraic evolutionary models that are based on such networks
Teachers’ Perceptions of Video-based Peer Coaching as a Mechanism for Professional Development Within Secondary Education
Get PDFEducation relies on the development and maintenance of teacher skills and classroom practice to develop student learning. Professional development is utilised within many UK schools and aims to develop learning within classrooms through the development of teachers’ pedagogical skills. However, significant challenges are found within current professional development cycles, such as the considerable time investment required for implementation and the common reluctance of teachers to engage with traditional professional development practices. This study investigates teachers’ perception of a peer coaching programme as a mechanism for professional development.
The coaching programme utilised a qualitative case study design to investigate the efficacy of peer coaching, incorporating video analysis to enhance reflective practices and professional development among teachers. Participants were placed into coaching partnerships (“Dyads”) and engaged in lesson observations and coaching sessions/conversations, which formed part of the peer coaching programme used in this thesis. The peer coaching programme employed Korthagen’s “Onion” Model of Reflective Practice (2017), involving layers of reflection to allow for deeper self-reflection of past experiences. Coaching sessions between the coaching dyads were used to foster a holistic approach to teacher development, utilising pre-existing expertise, emphasising trust, communication, and the integration of theory and practice. Data collection was completed across one academic year through semi-structured interviews with teachers pre-, during and post-peer coaching programme. The findings suggest that peer coaching can foster robust trust and communication among coaching partnerships, areas where traditional professional development methods often have been seen to fall short. Moreover, the video recordings were seen to facilitate a more precise examination of instructional practices, alleviating privacy concerns and encouraging open discussion among teachers. The results found that the coaching model could provide a reflective framework for professional development and illustrated four key themes: self-realisation and deeper thinking, questioning and challenging practice, sharing effective practices, and collaborative sense-making. Despite the increasing interest in peer coaching as a professional development intervention, the study emphasises the necessity for further research to optimise its effectiveness. Critical factors identified for successful peer coaching include the establishment of trust, effective communication, and reflective discourse, with video analysis serving as a vital tool to enhance the clarity of real-world teaching practices.
Key Words: Peer Coaching, Teacher Professional Development, Reflective Practice, Video Analysis, Collaborative Learning, Trust-Building, Pedagogical Discussion, Continuous Professional Development (CPD