Biology subjects

Davies, E.

Publications and source records attributed to Davies, E..

6 recordsLinked to original sources

bioRxiv2026

Optimised haemoglobin depletion improves clinical proteomics from dried blood spots

Equitable access to large sample cohorts for robust, high-throughput proteomics for biomarker discovery is a major barrier to widescale clinical implementation. Dried blood spots (DBS) offer a minimally invasive alternative to venous blood draws, enabling at-home microsampling (<50 {micro}L) for centralised analysis, thus enhancing research participation. This approach is particularly relevant for under-represented groups, including children, the elderly, minority backgrounds and those with long-term health conditions such as chronic kidney disease (CKD), where disease fluctuations may occur outside the clinic, and vein preservation is critical. Proteomic analysis has demonstrated great utility in monitoring disease progression, and for biomarker/therapeutic target discovery. However, liquid chromatography-tandem mass spectrometry (LC-MS/MS) of whole blood is hindered by the wide dynamic range and the relatively high abundance of proteins such as haemoglobin, compromising biomarker discovery. Here, we establish an optimised workflow for protein extraction and haemoglobin depletion from microsamples obtained using DBS, enabling sensitive and high-throughput proteomic analysis. We demonstrate that haemoglobin depletion increases protein identifications by [~]50%, mitigating ion suppression and dynamic range effects, enabling the identification of putative biomarkers from patients with stage 5 CKD on dialysis. We also evaluated a commercial cell-free DBS device which yielded a sample more representative of plasma compared to traditional DBS and enabled greater depletion of haemoglobin compared to traditional DBS with haemoglobin depletion methods. Our findings offer a scalable approach for biomarker discovery, facilitating remote, longitudinal clinical studies.

biochemistry↗

bioRxiv2026

First Usutu virus detections in wild birds in Scotland, 2025

In summer 2025, several Eurasian Blackbird (Turdus merula) deaths were reported on the Isle of Arran in Scotland. Initial investigation included post-mortem examination, where no diagnosis was achieved. Following Orthoflavivirus and avian paramyxovirus testing, Usutu virus RNA was detected in two Blackbirds by reverse transcription-PCR. Phylogenetic analysis identified Usutu virus Africa 3.2 lineage which clustered closely with existing UK detections, indicating geographic expansion rather than a new incursion. Subsequent surveillance confirmed the presence of several potential mosquito vector species.

microbiology↗

bioRxiv2025

The reproductive microbiome inhibits pollen germination in milkweed

We know very little about the reproductive microbiomes of plants. Microbes may play important roles in shaping pollination, fertilization, and seed production - processes which are important evolutionarily, ecologically, and agriculturally. Through a series of field and laboratory experiments, we show that the stigmatic microbiome in milkweeds influences the success of pollination. Isolation of individual bacterial and fungal taxa from stigmatic secretions allowed us to experimentally test their effects on pollen germination. These experiments demonstrate that individual taxa impact pollen differently, with many microbial taxa being neutral, but some being deleterious. Through isolation of microbes from the legs of pollinator insects we found that pollinators are a likely source for pollen-harmful bacterial taxa. Next, by utilizing a natural hybrid zone, we demonstrate species-specific responses to the stigmatic microbiome that be driving asymmetric patterns of gene-flow between species - with Asclepias exaltata being a better pollen host than A. syriaca. This study demonstrates that the reproductive microbiome is an underappreciated player in sexual reproduction of plants. Significance StatementThe results presented here demonstrate an important but previously unappreciated role of stigmatic microbes in plant sexual reproduction. This study demonstrates that the microbial taxa living in stigmatic secretions in milkweed impact pollen germination. We found that filtering out the microbes from stigmatic secretions of milkweed flowers dramatically increases pollen germination. Through isolating microbial taxa from both stigmatic secretions, and pollinator legs, we found that individual microbial taxa impact pollen differently, with many taxa being neutral, but some being deleterious. Finally, by utilizing a naturally occurring milkweed hybrid zone we demonstrated that microbial taxa in stigmatic secretions may be acting as asymmetric prezygotic barrier.

plant biology↗

bioRxiv2021

Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis

Extracellular matrix (ECM) stiffening with downstream activation of mechanosensitive pathways is strongly implicated in fibrosis. We previously reported that altered collagen nanoarchitecture is a key determinant of pathogenetic ECM structure-function in human fibrosis (Jones et al., 2018). Here, through human tissue, bioinformatic and ex vivo studies we show that hypoxia-inducible factor (HIF) pathway activation is a critical pathway for this process regardless of oxygen status (pseudohypoxia). Whilst TGF{beta} increased rate of fibrillar collagen synthesis, HIF pathway activation was required to dysregulate post-translational modification of fibrillar collagen, promoting bone-type cross-linking, altering collagen nanostructure, and increasing tissue stiffness. In vitro, knock down of Factor Inhibiting HIF (FIH) or oxidative stress caused pseudohypoxic HIF activation in normal fibroblasts. In contrast, endogenous FIH activity was reduced in fibroblasts from patients with lung fibrosis in association with significantly increased normoxic HIF pathway activation. In human lung fibrosis tissue, HIF mediated signalling was increased at sites of active fibrogenesis whilst subpopulations of IPF lung mesenchymal cells had increases in both HIF and oxidative stress scores. Our data demonstrate that oxidative stress can drive pseudohypoxic HIF pathway activation which is a critical regulator of pathogenetic collagen structure-function in fibrosis.

cell biology↗

bioRxiv2020

The Planarian Anatomy Ontology: A resource to connect data within and across experimental platforms

As the planarian Schmidtea mediterranea (Smed) gains popularity as a research organism, the need for standard anatomical nomenclature is increasingly apparent. A controlled vocabulary streamlines data annotation, improves data organization, and enhances cross-platform and cross-species searchability. We created the Planarian Anatomy Ontology (PLANA), an extendable framework of defined Smed anatomical terms organized using relationships. The most current version contains over 800 terms that describe Smed anatomy from subcellular to system-level across all life cycle stages, in intact animals, and regenerating body fragments. Terms from other anatomy ontologies were imported into PLANA to promote ontology interoperability and comparative anatomy studies. To demonstrate the utility of PLANA for data curation, we created web-based resources for planarian embryogenesis, including a staging series and molecular fate mapping atlas, as well as a searchable Planarian Anatomy Gene Expression database, which integrates a variety of published gene expression data and allows retrieval of information of all published sequences associated with specific planarian anatomical regions. Finally, we report methods for continued curation of PLANA, providing a path for expansion and evolution of this community resource. Summary StatementWe report construction of an anatomy ontology for an emerging research organism and show its use to curate and mine data across multiple experimental platforms.

developmental biology↗

bioRxiv2019

Associations of ‘Relative corticosterone deficiency’ with genetic variation in CYP17A1 and metabolic syndrome features

Context and objectiveCommon genetic variants in CYP17A1 associate with higher blood pressure, putatively from impaired 17-hydroxylase activity and mineralocorticoid excess. However, the same variants protect against obesity and insulin resistance. We tested whether CYP17A1 variants that enhance 17-hydroxylase activity cause relative corticosterone deficiency. Since corticosterone is thought to contribute disproportionately to negative feedback in the hypothalamic-pituitary-adrenal axis, we also tested whether lower corticosterone associates with higher cortisol and hence with metabolic syndrome.\n\nDesignCross-sectional studies within the population-based Orkney Complex Disease Study (ORCADES; n=2018), VIKING Health Study Shetland (VIKING; n=2098), East Hertfordshire study (EHERTS; n=279), Edinburgh Type 2 Diabetes Study (ET2DS; n=903), and the Swiss Kidney Project on Genes in Hypertension (SKIPOGH; n=888).\n\nOutcome measuresCortisol and corticosterone in morning plasma samples in ORCADES, VIKING and ET2DS, and in EHERTS in plasma following overnight dexamethasone suppression (0.25mg) and 30 mins after ACTH1-24 (1{micro}g); cortisol and corticosterone metabolites in day and night urine samples in SKIPOGH. Features of the metabolic syndrome including body mass index, systolic blood pressure, lipid profile, fasting glucose, fasting insulin and HOMA-IR.\n\nResultsIn ORCADES, ET2DS and SKIPOGH, CYP17A1 variants were associated with corticosterone:cortisol ratio. In ORCADES, VIKING and ET2DS there were consistent associations of morning plasma cortisol and corticosterone with BMI, blood pressure, lipid profile, fasting glucose and HOMA-IR. In EHERTS, however, after dexamethasone suppression and ACTH1-24 stimulation, impaired glucose tolerance and insulin sensitivity were associated with higher cortisol but lower corticosterone. Similarly, in SKIPOGH, low corticosterone:cortisol metabolite ratios were associated with high BMI and dyslipidemia.\n\nConclusions Relative corticosterone deficiency, due to a primary alteration in adrenal steroidogenesis favouring cortisol over corticosterone, may mediate the associations of genetic variation in CYP17A1 with metabolic syndrome. However, additional determinants of variation in plasma corticosterone are likely to explain its generally positive associations with features of metabolic syndrome.

epidemiology↗