Generative Artificial Intelligence (GenAI) is rapidly transforming the landscape of higher education, offering novel opportunities for personalised learning and innovative assessment methods. This paper explores the dual-edged nature of GenAI’s integration into educational practices, focusing on both its potential to enhance student engagement and learning outcomes and the significant challenges it poses to academic integrity and equity. Through a comprehensive review of current literature, we examine the implications of GenAI on assessment practices, highlighting the need for robust ethical frameworks to guide its use. Our analysis is framed within pedagogical theories, including social constructivism and competency-based learning, highlighting the importance of balancing human expertise and AI capabilities. We also address broader ethical concerns associated with GenAI, such as the risks of bias, the digital divide, and the environmental impact of AI technologies. This paper argues that while GenAI can provide substantial benefits in terms of automation and efficiency, its integration must be managed with care to avoid undermining the authenticity of student work and exacerbating existing inequalities. Finally, we propose a set of recommendations for educational institutions, including developing GenAI literacy programmes, revising assessment designs to incorporate critical thinking and creativity, and establishing transparent policies that ensure fairness and accountability in GenAI use. By fostering a responsible approach to GenAI, higher education can harness its potential while safeguarding the core values of academic integrity and inclusive education.

Common polymorphisms in complement alternative pathway (AP) proteins C3 (C3_R102G), factor B (fB_R32Q), and factor H (fH_V62I) are associated with age-related macular degeneration (AMD) and other pathologies. Our published work showed that fB_R32Qinfluences C3 convertase formation, whereas fH_V62Iaffects factor I cofactor activity. Here we show how C3_R102G(C3S/F) influences AP activity. In hemolysis assays, C3_102Gactivated AP more efficiently (EC₅₀C3_102G: 157 nM; C3_102R: 191 nM;P< 0.0001). fB binding kinetics and convertase stability were identical, but native and recombinant fH bound more strongly to C3b_102R(K_DC3b_102R: 1.0 μM; C3b_102G: 1.4 μM;P< 0.0001). Accelerated decay was unaltered, but fH cofactor activity was reduced for C3b_102G, favoring AP amplification. Combining disease “risk” variants (C3_102G, fB_32R, and fH_62V) in add-back assays yielded sixfold higher hemolytic activity compared with “protective” variants (C3_102R, fB_32Q, and fH_62I;P< 0.0001). These data introduce the concept of a functional complotype (combination of polymorphisms) defining complement activity in an individual, thereby influencing susceptibility to AP-driven disease.

Metabolic pathways that regulate T-cell function show promise as therapeutic targets in diverse diseases. Here, we show that at rest cultured human effector memory and central memory CD4+ T-cells have elevated levels of glycolysis and oxidative phosphorylation (OXPHOS), in comparison to naïve T-cells. Despite having low resting metabolic rates, naive T-cells respond to TCR stimulation with robust and rapid increases in glycolysis and OXPHOS. This early metabolic switch requires Akt activity to support increased rates of glycolysis and STAT5 activity for amino acid biosynthesis and TCA cycle anaplerosis. Importantly, both STAT5 inhibition and disruption of TCA cycle anaplerosis are associated with reduced IL-2 production, demonstrating the functional importance of this early metabolic program. Our results define STAT5 as a key node in modulating the early metabolic program following activation in naive CD4+ T-cells and in turn provide greater understanding of how cellular metabolism shapes T-cell responses.

Linking immunometabolic adaptation to T-cell function provides insight for the development of new therapeutic approaches in multiple disease settings. T-cell activation and downstream effector functions of CD4+ and CD8+ T-cells are controlled by the strength of interaction between the T-cell receptor (TCR) and peptides presented by human leukocyte antigens (pHLA). The role of TCR-pHLA interactions in modulating T-cell metabolism is unknown. Here for the first time we explore the relative contributions of the main metabolic pathways to functional responses in human CD4+ and CD8+ T-cells. Increased expression of hexokinase II accompanied by higher basal glycolysis is demonstrated in CD4+ T-cells; cytokine production in CD8+ T-cells is more reliant on oxidative phosphorylation. Using antigen-specific CD4+ and CD8+ T cell clones and altered peptide ligands we demonstrate that binding affinity tunes the underlying metabolic shift. Overall this study provides important new insight into how metabolic pathways are controlled during antigen-specific activation of human T-cells.

Genomic disorders affecting the genes encoding factor H (fH) and the 5 factor H related proteins have been described in association with atypical hemolytic uremic syndrome. These include deletions of CFHR3, CFHR1, and CFHR4 in association with fH autoantibodies and the formation of a hybrid CFH/CFHR1 gene. These occur through nonallelic homologous recombination secondary to the presence of large segmental duplications (macrohomology) in this region. Using multiplex ligation-dependent probe amplification to screen for such genomic disorders, we have identified a large atypical hemolytic uremic syndrome family where a deletion has occurred through microhomology-mediated end joining rather than nonallelic homologous recombination. In the 3 affected persons of this family, we have shown that the deletion results in formation of a CFH/CFHR3 gene. We have shown that the protein product of this is a 24 SCR protein that is secreted with normal fluid-phase activity but marked loss of complement regulation at cell surfaces despite increased heparin binding. In this study, we have therefore shown that microhomology in this area of chromosome 1 predisposes to disease associated genomic disorders and that the complement regulatory function of fH at the cell surface is critically dependent on the structural integrity of the whole molecule.

Objectives. Lactoferrin is an iron-binding protein that is released from activated neutrophils at sites of inflammation and has anti-microbial as well as anti-inflammatory properties. This study set out to determine whether lactoferrin can delay neutrophil apoptosis and could act as a survival factor for neutrophils in SF. Methods. Human peripheral blood and SF neutrophils were incubated with iron-free lactoferrin and apoptosis determined after 9 h. SF from patients with RA was added to isolated neutrophils, with or without immunodepletion of lactoferrin, and effects on neutrophil apoptosis determined. Levels of lactoferrin in SF were assessed and related to disease duration and markers of disease activity. Results. Iron-free lactoferrin significantly delayed apoptosis of peripheral blood neutrophils, in a concentration-dependent manner after 9 h in culture (P < 0.04). Lactoferrin could also delay apoptosis of neutrophils isolated from SF of patients with RA. SF from patients with established RA delayed apoptosis of peripheral blood neutrophils and this effect was significantly reduced by depletion of lactoferrin (P < 0.03). Lactoferrin levels in SF from patients with established RA did not correlate with disease severity, but did correlate with markers of inflammation (CRP) and with the presence of RF. SF from patients with arthritis of <12 weeks duration did not contain significant levels of lactoferrin. Conclusion. Lactoferrin contributes to extended neutrophil survival in the rheumatoid joint in the established phase of RA but not in very early arthritis.