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Kidney tumoroid characterisation by spatial mass spectrometry with same-section multiplex immunofluorescence uncovers tumour microenvironment lipid signatures associated with aggressive tumour phenotypes
Get PDFFunding: The work was supported by the KATY project (D.J.H.) that received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 101017453. G.M.Z. was supported by a Melville Trust PhD Scholarship and H.A. by a University of St Andrews Sanctuary Scholarship. We are grateful to NHS Lothian Biorepository for facilitating tissue collection.Renal cell carcinoma (RCC) incidence is rising, and treatment remains challenging unless surgery is curative. Tumour heterogeneity contributes to resistance against both chemotherapy and immune checkpoint inhibitors, underscoring the need to better understand the complex tumour microenvironment (TME). While tumour models derived from cancer tissue from patients have advanced cancer research, they often fail to capture functional RCC heterogeneity and key TME components. We developed a 3D model system with a high success rate from resected tumour, retaining cancer, stromal, and immune cell populations. This system is fully compatible with advanced imaging technologies, including mass spectrometry imaging (MSI) and live-cell multiplex imaging. By integrating static spatial analysis with dynamic live-cell visualisation, our system provides unique insights into tumour heterogeneity, microenvironment metabolic crosstalk, and real-time cellular responses. Phenotypic characterization of the tumoroids showed strong histological resemblance to the original resected tissue, indicating that the tumoroids are reflective of the tumour in vivo and suitable as a representative model system. Additionally, DESI-MSI revealed distinct lipidomic profiles within patient-derived ccRCC tumoroids, capturing spatial metabolic heterogeneity reflective of the primary tissue. Lipid signatures varied across tumour regions, with phospholipid subclasses distinguishing epithelial, endothelial, and highly proliferative cell populations. Notably, non-clear cell regions exhibited reduced lipid droplet and fatty acid content, aligning with aggressive tumour phenotypes.Peer reviewe
Form and content : a defence of aesthetic values in science
Get PDFThose who wish to defend the role of aesthetic values in science face a dilemma: aesthetic language is either used metaphorically for what are ultimately epistemic features, or it is used literally, but the importance of such values for science is unclear. This article introduces a new account that gets around this problem by considering an overlooked source of aesthetic value in science: the relation between form and content. A fit between the content of a thought experiment and the way in which that content is formulated can have important epistemic payoffs by contributing to scientific understanding.Peer reviewe
Developing Scotland’s first green health prescription pathway : a one-stop shop for nature-based intervention referrals
Get PDFIntroduction: Lifestyle modifications are part of comprehensive treatment plans to help manage the symptoms of pre-existing chronic conditions. However, behavior change is notoriously difficult as patients often lack the necessary support. The present manuscript outlines the development of a Green Health Prescription pathway that was designed to link patients with appropriate lifestyle interventions (i.e., nature-based interventions) and to support attendance. Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis was undertaken in three focus groups (i.e., National Health Service healthcare professionals, service-users, and nature-based intervention delivery partners) to highlight areas of strength and weakness within the proposed pathway prior to delivery. The SWOT analyses revealed that the pathway was supported by all three focus groups. Weaknesses and threats were identified including sustainability of nature based interventions in terms of funding, the need to connect patients with appropriate interventions based on their physical and mental health needs, and the requirement to have a “one-stop shop” for information to ensure that the pathway was accessible for all service-users and healthcare professionals. Results were addressed and considered throughout the development of the pathway. Discussion: The Green Health Prescription pathway was launched in 2019 and gave patients the ability to receive a prescription from a healthcare professional, community service, or to self-refer. The pathway allows patients to contact a consultant, via a telephone service, who is trained to match them with a programme that the patient believes will be enjoyable and that fits thePeer reviewe
The value of surprise in science
Get PDFScientific results are often presented as ‘surprising’ as if that is a good thing. Is it? And if so, why? What is the value of surprise in science? Discussions of surprise in science have been limited, but surprise has been used as a way of defending the epistemic privilege of experiments over simulations. The argument is that while experiments can ‘confound’, simulations can merely surprise (Morgan, 2005). Our aim in this paper is to show that the discussion of surprise can be usefully extended to thought experiments and theoretical derivations. We argue that in focusing on these features of scientific practice, we can see that the surprise-confoundment distinction does not fully capture surprise in science. We set out how thought experiments and theoretical derivations can bring about surprises that can be disruptive in a productive way, and we end by exploring how this links with their future fertility.Peer reviewe
Vacancy ordering and polytypism in B-site deficient halide perovskites
No full textB-site deficient halide perovskites show promising optoelectronic properties as potential candidates for the replacement for conventional lead-based halide perovskites. To further understand the relationship between crystal structure and properties, it would be of great interest to explore B-site deficient halide perovskites with various vacancy distributions. This work focuses on the preparation and characterisation of novel B-site deficient halide perovskites with unusual vacancy ordering.
The successful preparation of Cs₄CuSb₂Cl₁₂ in 2017 provided insight into the study of cubic closed packed B-site deficient halide perovskites. Theoretical screening and experimental work were carried out in this study to explore other potential A₄B’²⁺B³⁺₂X₁₂ halide perovskites. One novel compound Cs₄MnBi₂Cl₁₂ was synthesised and analysed, with typical d-d transition induced photoluminescence (PL) at 602 nm activated by octahedral coordinated 3d⁵ Mn²⁺.
By manipulating the fraction of B-site vacancies, another novel B-site deficient halide perovskite Cs₁₀MnSb₆Cl₃₀ with unusual one-dimensional 10H (hcccc)₂ structure was synthesised and studied. A similar d-d transition induced PL was observed at 620 nm. However, an enhancement of the quantum yield in comparison with previously reported Cs₄MnSb₂Cl₁₂ suggested that this is due to the different vacancy ordering and reduced dimensionality of octahedral connectivity. Preliminary DFT calculations of the electronic structure of Cs₁₀MnSb₆Cl₃₀ suggested an indirect band gap of 2.69 eV for this compound.
By using azetidinium (Az⁺) as the A-site cation, one novel B-site deficient perovskite polytype with a 6H (hcc)₂ layered structure was observed in Az₃Sb₂Cl₉ and Az₃Sb₂Br₉. The unique vacancy distribution formed an intrinsically polar structure, which was further confirmed by the converse piezoelectric effect. Variable temperature structural analysis and property measurements revealed several phase transitions from the hexagonal prototypical structure to an orthorhombic superstructure between 300 K and 20 K for both compounds. A tuneable band gap and preferential site occupation of chlorine and bromine anions were also observed in the solid-solution Az₃Sb₂Cl₉₋ₓBrₓ.
The other azetidinium based halides were preliminarily investigated. Az₃Sb₂l₉, Az₃Bi₂Br₉ and Az₃Bi₂I₉ showed typical zero-dimensional 6H (hcc)₂ perovskite structure with isolated octahedral dimers; whereas Az₂BiCl₅ and Az₂BiBr₅ were found to adopt non-perovskite cis-connected chain structures
Designing a virtual museum ecosystem for the Cloud
Get PDFFunding: This project is funded by the European Union under the Horizon EU research and innovation programme HORIZON-CL2-2023-HERITAGE-ECCCH-01 (A European Collaborative Cloud for Cultural Heritage - 2023) under grant agreement No. 1011580811 HERITALISE).Digital exhibits are often commissioned from specialist organisations for a premium price and only available to prestigious national and international organisations that have the budget to match. Yet developments in underlying technologies, such as commodity computers, mobiles and networks, are increasingly capable of delivering rich heritage experiences. Consequently, the possibility of immersive and mobile technologies becoming part of the normal offering of community museums is in reach. A virtual museum ecosystem, which empowers community-based museums to embrace technologies to digitally enhance the capacities of a museum supporting the research, collection, curation and communication of heritage, has the potential both to contribute to sustainable development as well as mitigate against the threats to heritage
Individual pluralism : a theory of persistence
Get PDFThis thesis introduces and develops a theory of persistence termed ‘individual pluralism’. According to individual pluralism, individuals persist through time as pluralities of instantaneous entities connected by genidentity relation and are subject to certain criteria of individuation. The theory rejects the existence of temporally extended entities and holds that all entities are instantaneous. Initially, the thesis clarifies the concept of individuality by differentiating it from related terms such as ‘entity’ and ‘object’. Drawing on the ideas of Kurt Lewin and E.J. Lowe, it characterizes individuals as pluralities of instantaneous entities collectively instantiating sorts, thereby resolving tensions inherent in traditional singular conceptions of individuality. The thesis then explores the characteristics of genidentity and focuses on the question of whether genidentity is an ontological dependence relation or grounding relation. The conclusion is that it depends on whether we think that ontological dependence or grounding has priority against the other, and genidentity is the relation that has priority. Additionally, the thesis investigates criteria of individuation, particularly emphasizing their application to artifactual sorts. It argues that individuation for artifacts significantly depends on the creators’ intentions and the artifacts’ sort-related functions, explicitly excluding non-sort-related or idiosyncratic functions. Finally, the practical applications of individual pluralism are demonstrated through its solutions to classic metaphysical problems of persistence, including the problem of change, the problem of diachronic identity, and the problem of coincidence. Individual pluralism resolves these issues by redefining identity and change within a plural logic framework, focusing on collective actions and dynamic processes rather than static property changes
Mid-Devonian ocean oxygenation enabled the expansion of animals into deeper-water habitats
Get PDFFunding: M.A.K. was supported by an NSF Graduate Research Fellowship, an Agouron Institute Postdoctoral Fellowship, and NSF grant MGG-2054892 (to F.L.H.T.). Additional support was provided by the NASA Astrobiology Institute Virtual Planetary Laboratory Grant 80NSSC19K0829.The oxygenation history of Earth’s surface environments has had a profound influence on the ecology and evolution of metazoan life. It was traditionally thought that the Neoproterozoic Oxygenation Event enabled the origin of animals in marine environments, followed by their persistence in aerobic marine habitats ever since. However, recent studies of redox proxies (e.g., Fe, Mo, Ce, I) have suggested that low dissolved oxygen levels persisted in the deep ocean until the Late Devonian, when the first heavily wooded ligniophyte forests raised atmospheric O2 to modern levels. Here, we present a Paleozoic redox proxy record based on selenium enrichments and isotope ratios in fine-grained siliciclastic sediments. Our data reveal transient oxygenation of bottom waters around the Ediacaran–Cambrian boundary, followed by predominantly anoxic deep-water conditions through the Early Devonian (419 to 393 Ma). In the Middle Devonian (393 to 382 Ma), our data document the onset of permanent deep-ocean oxygenation, coincident with the spread of woody biomass across terrestrial landscapes. This episode is concurrent with the ecological occupation and evolutionary radiation of large active invertebrate and vertebrate organisms in deeper oceanic infaunal and epifaunal habitats, suggesting that the burial of recalcitrant wood from the first forests sequestered organic carbon, increased deep marine oxygen levels, and was ultimately responsible for the “mid-Paleozoic marine revolution.”Peer reviewe
Quantifying national burdens of foodborne disease-Four imperatives for global impact
Get PDFEstimates of national burdens of the foodborne disease (FBD) inform country-level food safety policies, ranking infectious and non-infectious FBD hazards in terms of health and socioeconomic impact to mitigate FBD burdens. Using relevant publications on FBD burdens from scientific literature, this review contends that four major imperatives (health, economic, planetary boundaries, governance) argue for a sustainable programme to quantify national FBD burdens. FBD disproportionately affects children under five years of age, and low- and middle-income countries. The economic costs are significant and include medical care, child development, lost productivity and international trade losses. Climatic changes and environmental contamination cause socio-ecological disruptions, increasing risk factors for FBD. Good governance promotes food safety initiatives, addressing in part under-diagnosis and underreporting. Strengthening national policies on FBD surveillance and burden estimation can promote food safety policies and address the global and national imperatives for FBD control. Evidence-based educational and regulatory interventions for FBD can promote improvements in the health and socioeconomic circumstances of the most vulnerable.Peer reviewe
Detections of rare species lead citizen scientists to initiate data recording
Get PDFFunding: Louis Backstrom and Rachel Drake received PhD scholarship funding from CREEM, the Centre for Research into Ecological and Environmental Modelling.Aim: Citizen science data are increasingly used to monitor biodiversity but come with several challenges that can impair accurate ecological conclusions. We explore how observers' preferences for certain species over others bias the initiation of survey efforts and assess the extent of this sampling bias in semi-structured citizen science datasets. We investigate the effects of this bias on occupancy model-based species distribution models and offer suggestions for mitigating this when analysing citizen science data. Location: Great Britain, with methods applicable to citizen science datasets worldwide. Methods: We assess observer species preferences in list initiation via two methods: (1) indirectly through exploration of the relationship between species rarity and survey duration and (2) directly through analysis of the first-recorded species on surveys. We use these results to assess the impact of list-initiation sampling bias on occupancy models of 132 common breeding birds across Britain. Results: We find evidence for list-initiation sampling bias in British eBird and BirdTrack data. This bias is driven by observer preferences for certain species over others, with species preferences correlated with species rarity. This bias was stronger in short-duration surveys, and removing short surveys to remove these biased lists had limited impacts on occupancy models. Conclusions: Citizen science schemes projects that allow observers freedom in how they observe and record biodiversity consequently have more heterogeneous datasets. Observer species preferences lead to biased initiation of surveys and consequent overreporting of some species. Although we find limited effects of this bias on occupancy models in our study, we nevertheless suggest analysts consider its possible effects when exploring and analysing citizen science data.Peer reviewe
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