Biology subjects

Stewart, A. J.

Publications and source records attributed to Stewart, A. J..

5 recordsLinked to original sources

bioRxiv2026

Perceived Risk and Barriers to Open and Responsible Research Across Fifteen UK Universities

Open research practices are increasingly promoted to improve research transparency, reproducibility, accessibility, and societal impact. Despite growing support from research funders, institutions, and policy initiatives, adoption remains uneven across disciplines and research communities. This study examined perceived risks and barriers associated with 14 FORRT Guideline areas using qualitative responses from the UK Reproducibility Network Open and Transparent Research Practices Survey (N = 2,567), conducted across 15 UK higher education institutions. Free-text responses describing risks and barriers were analysed using inductive thematic analysis. A total of 3,951 relevant comments generated 3,433 coded references to barriers and risks. Three interconnected clusters emerged. Individual concerns included lack of motivation, fear of losing intellectual credit, and concerns about exposing mistakes and criticism. Systemic and institutional barriers included lack of time and resources, inadequate infrastructure, insufficient training and support, lack of incentives and recognition, unclear guidance, disciplinary and methodological challenges, and tensions between open practices and intellectual property requirements. Ethical and quality-related concerns included risks to participant confidentiality and privacy, challenges associated with sensitive data, concerns about inappropriate application of open research practices across different research traditions, perceived impacts on research quality and innovation, and potential effects on public trust in research. Lack of time and resources was the most frequently reported barrier. Across responses, barriers were commonly described as interdependent, with shortcomings in funding, infrastructure, institutional support, incentives, and training reinforcing one another. Respondents largely supported the principles underpinning open research but highlighted substantial practical, professional, and ethical challenges to implementation. These findings suggest that increasing open research adoption requires more than policy mandates or awareness-raising activities. Sustainable uptake will depend on aligned incentives, adequate infrastructure and support, recognition of methodological diversity, and approaches that enable openness to be implemented responsibly across different research contexts.

scientific communication and education↗

bioRxiv2026

L-pentahomoserine correlates with therapy outcome in esophageal cancer and promotes metabolic adaptations that support cell survival under nutrient-deprived conditions

Esophageal adenocarcinoma (EAC) is the sixth-leading cause of cancer-related death. Although pyrimidine analogue-based neoadjuvant and adjuvant therapies are widely used, patient responses remain variable. Emerging evidence indicates that bacteria-derived metabolites influence tumor biology and therapy outcomes. To identify non-canonical plasma metabolites linked to cancer biology, we performed correlation analyses between untargeted metabolomics profiles and overall survival. This approach revealed a bacterial metabolite called L-pentahomoserine, or L-2-amino-5-hydroxypentanoic acid (L-2A5HPA), to be positively associated with overall survival. Notably, L-2A5HPA promoted cell survival under nutrient limitation by redirecting glucose metabolism towards aspartate and pyrimidine biosynthesis. In vitro, L-2A5HPA uptake varied among cell lines and was controlled by stereospecific transporters. Furthermore, metabolic profiling in mouse models of liver cancer showed different levels of L-2A5HPA and a strong correlation with pyrimidine intermediates, dihydroorotate and orotate. The link between L-2A5HPA, pyrimidine nucleotide metabolism, and cell survival provides mechanistic insight into its association with patient outcome. Our findings position L-2A5HPA as a metabolite with potential to become a prognostic biomarker for EAC and underscores its role in metabolic adaptation under nutrient-deprived conditions.

cancer biology↗

bioRxiv2022

Uncertainty favors an induced immune response to infection

Organisms use constitutive or induced defenses against pathogens, parasites, and herbivores. Constitutive defenses are constantly on, whereas induced defenses are activated upon exposure to an enemy. Constitutive and induced defenses each have costs and benefits, which can affect the type of defense that evolves in response to pathogens. Previous models that compared the two lacked mechanistic details about host defense, did not consider pathogen proliferation rates, or lacked both features. To address this gap, we developed a detailed mechanistic model of the well-characterized Drosophila melanogaster immune signaling network. We evaluated the factors favoring the evolution of constitutive and induced defenses by comparing the fitness of each strategy under stochastic fly-bacteria interactions. We show that an induced defense is favored when bacteria are at low density, heterogeneously distributed, or have fluctuating distributions in ways that depend on the bacterial proliferation rate. Our model also predicts that the specific negative regulators that optimize the induced response depend on the bacterial proliferation rate. We therefore conclude that an induced immune defense is favored in environments where bacterial encounters are uncertain--because of heterogeneity in spatial or temporal distributions--but that benefit depends on the mechanism of induction and pathogen properties.

evolutionary biology↗

bioRxiv2020

Differential Gene Expression Analysis and Cytological Evidence Reveal a Sexual Stage of an Amoeba with Multiparental Cellular and Nuclear Fusion

Sex is a hallmark of eukaryotes but its evolution in microbial eukaryotes is poorly elucidated. Recent genomic studies revealed microbial eukaryotes possess genetic toolkit necessary for sexual reproduction. However, the mechanism of sexual development in a majority of microbial eukaryotes including amoebozoans is poorly characterized. The major hurdle in studying sex in microbial eukaryotes is lack of observational evidence, primarily due to its cryptic nature. In this study, we used a tractable fusing amoeba, Cochliopodium, to investigate sexual development using stage specific Differential Gene Expression (DGE) and cytological analyses. Both DGE and cytological results showed that most of the meiosis and sex-related genes are upregulated in Cochliopodium undergoing fusion in laboratory culture. Relative gene ontology (GO) category representations in unfused (single) and fused cells revealed functional skew of the fused transcriptome toward DNA metabolism, nucleus and ligases that are suggestive of a commitment to sexual development. While single cells GO categories were dominated by metabolic pathways and other processes indicative of vegetative phase. Our study provides strong evidence that the fused cells represent a sexual stage in Cochliopodium. Our findings have further implications in understanding the evolution and mechanism of inheritance involving multiparents in other eukaryotes with similar reproductive strategy.View Full Text

developmental biology↗

bioRxiv2019

Plasma non-esterified fatty acids contribute to increased coagulability in type-2 diabetes through altered plasma zinc speciation

Zn2+ is an essential regulator of coagulation and its availability in plasma is fine-tuned through buffering by human serum albumin (HSA). Non-esterified fatty acids (NEFAs) transported by HSA reduce its ability to bind/buffer Zn2+. This is important as plasma NEFA levels are elevated in type-2 diabetes mellitus (T2DM) and other diseases with an increased risk of developing thrombotic complications. The presence of 5 mol. eq. of myristate, palmitate, stearate, palmitoleate and palmitelaidate reduced Zn2+ binding to HSA. Addition of myristate and Zn2+ increased thrombin-induced platelet aggregation in platelet-rich plasma and increased fibrin clot density and clot time in a purified protein system. The concentrations of key saturated (myristate, palmitate, stearate) and monounsaturated (oleate, vaccinate) NEFAs positively correlated with clot density in subjects with T2DM (and controls). Collectively, these data strongly support the concept that elevated NEFA levels contribute to an increased thrombotic risk in T2DM through dysregulation of plasma zinc speciation.

biochemistry↗