Biology subjects

Fraser, E.

Publications and source records attributed to Fraser, E..

6 recordsLinked to original sources

bioRxiv2026

Breathlessness catastrophising after COVID-19 involves both interoceptive and visceromotor connectivity

Persistent breathlessness is common after COVID-19, yet its severity typically correlates weakly with objective clinical measures. This discordance is often attributed to perceptual inference amplified by anxiety. Because breathing involves a closed perception-action loop, breathlessness may also reflect alterations in interoceptive and visceromotor pathways. We acquired 7-tesla resting-state functional MRI in 53 post-COVID patients with varying breathlessness and estimated functional connectivity across 18 pre-defined interoceptive and visceromotor regions. Linear regression identified two connections associated with breathlessness catastrophising: reduced dorsal periaqueductal grey-posterior insula (dPAG-PoI1) and increased basolateral amygdala-dorsal anterior cingulate (BLA-dACC) connectivity. The dPAG-PoI1 association was stronger in patients who had required mechanical ventilation, whereas the BLA-dACC association was attenuated at higher generalised anxiety. These findings are consistent with two potentially separable contributions to symptom burden: weakened interoceptive signalling between brainstem and sensory cortex, and heightened visceromotor influence of threat processing on autonomic control, rather than anxiety-driven misperception alone.

neuroscience↗

bioRxiv2026

Capillary-based Subcellular Sampling Uncovers the Stress Granule Proteome in Single Cells

Many diseases arise from dysfunction within specific organelles or biomolecular condensates, highlighting the value of analysing proteins at subcellular resolution to uncover new biological mechanisms. We report a novel capillary-based subcellular sampling workflow coupled with liquid chromatography-mass spectrometry (LC-MS) for proteomic analysis of defined subcellular regions of individual cells. We applied this methodology to stress granules (SGs), membrane-less biomolecular condensates that form in response to cellular stress (including viral infection), and are implicated in infection, neuropathology and cancer. Comprehensive characterisation of SG protein composition remains limited by technical challenges associated with bulk purification, including loss of spatial context, dynamic behaviour and contamination from cytosolic material. Using our novel method, we identified a high-confidence set of 405 SG-associated proteins, including 46 established SG residents alongside numerous previously unreported candidates. Functional enrichment analysis revealed pathways consistent with known SG biology, while comparison with an independent cytosolic proteome dataset demonstrated minimal overlap, supporting the specificity of the sampling strategy. Selected novel SG protein candidates (AHNAK2, DDX39B, NUDT1 and FKBP2) were validated using immunofluorescence microscopy. These findings establish capillary-based subcellular sampling as a viable approach for proteomic analysis of SGs with preserved spatial context and provide a framework for analysing other subcellular compartments. Table of contentsWe report an LC-MS-based capillary sampling workflow for proteomic analysis of subcellular structures within single cells. This methodology identified 405 high-confidence stress granule-associated proteins, including 46 previously established and numerous novel candidates. The approach demonstrated high specificity and preserved spatial context, expanding the capabilities of subcellular proteomics. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=55 SRC="FIGDIR/small/724230v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1fa0bb0org.highwire.dtl.DTLVardef@1158524org.highwire.dtl.DTLVardef@1d82812org.highwire.dtl.DTLVardef@2ee4d9_HPS_FORMAT_FIGEXP M_FIG C_FIG Figure made in Biorender.com.

cell biology↗

bioRxiv2025

Efficacy and safety evaluation of artificial intelligence-identified antimicrobial peptides for use against avian pathogenic Escherichia coli in the poultry industry

The overuse of antibiotics in both veterinary and human medicine has resulted in the emergence of antibiotic-resistant bacteria, prompting a search for effective alternatives. Antimicrobial peptides (AMP) are short, often cationic, peptide-based molecules with antimicrobial and immunomodulatory activity, which makes them promising alternatives to conventional antibiotics in poultry production. From a prior machine-learning-guided screen of 875 candidate AMPs, 62 exhibited activity against avian pathogenic Escherichia coli (APEC) and low in vitro hemolytic and cytotoxic activity. We selected three lead AMPs from this list (named TeRu4, TeBi1, and PeNi4), and evaluated their in vitro and in vivo efficacy, safety, and immunomodulatory potential for use in poultry farming. In animal experiments, AMPs were administered via in ovo injection on day 18 of embryonic development. In APEC challenge trials, yolk sacs were inoculated with APEC post-hatch to assess early chick mortality, while in pen trials, birds were raised in a commercial production setting for 35 days. For challenged birds, TeBi1 (10 g/egg) significantly reduced bacterial detection in the air sac and pericardium, increased body weight by 50% and reduced cytokine transcript levels by 10-30% on day 7 post hatch. In HD11 chicken macrophage-like cultured cells, TeRu4 (16 g/mL) suppressed lipopolysaccharide (LPS)-induced pro-inflammatory cytokine transcript levels. In pen trials, TeRu4 (20 g/egg) increased the survival probability of female birds by 4.9%, while TeBi1 (20 g/egg) increased the survival probability of all birds by 4.4%, by day 35. Gene expression analysis revealed AMP- and sex-specific cytokine responses. In pen trials, no significant differences were observed in mean weights, feed conversion ratio (FCR), and flock uniformity on day 35. These findings demonstrate that the three selected AMPs are safe antibiotic alternatives that improve survival, modulate immune responses, and maintain normal growth performance in broiler chickens.

microbiology↗

bioRxiv2024

Unusual migratory strategy a key factor driving interactions at wind energy facilities in at-risk bats

Seasonal movement strategies are poorly understood for most animals, impeding broader understanding of processes underlying migration and limiting practical conservation needs. Here we develop and implement a framework for integrating multiple sources of endogenous markers, in particular stable hydrogen isotope data, that capture and scale dynamics from the movements of individuals to that of continental migration. We assembled and integrated thousands of new isotopic measurements from bat fur with existing datasets and applied this framework to reveal migratory patterns of three broadly distributed bat species most at risk for fatalities at wind energy facilities. Our findings show that the species comprising the lowest proportion of wind turbine fatalities (silver-haired bats) exhibits expected movements to lower latitudes in autumn and higher latitudes in spring. Surprisingly, the two species with higher wind turbine fatality rates (hoary and eastern red bats) have more complex movements, including significant movement to higher latitudes during autumn. We term this unique strategy "pell-mell" migration, during which some individuals are as likely to move to higher latitudes as lower latitudes, relative to their individual summering grounds, in early autumn, after which they move to similar or lower latitudes to overwinter. The pell-mell migratory period corresponds with peak fatalities at wind energy facilities, and bats moving northward during autumn are associated with mortality at those facilities. Our results provide direct support for the hypothesis that bat fatalities at wind energy facilities are related to migration and highlight the importance of migratory distance as an ultimate driver of increased interactions with wind energy facilities, which appears significantly greater for species that travel widely across latitudes in the autumn.

ecology↗

bioRxiv2022

Case Study of Single-cell Protein Activity Based Drug Prediction for Precision Treatment of Cholangiocarcinoma

Cholangiocarcinoma is a rare, aggressive malignancy with limited treatment options, due to a paucity of actionable mutations and low response to immune checkpoint inhibitors. Furthermore, its extreme heterogeneity prevents identification of actionable dependencies from bulk-tissue profiles. To address these challenges, we introduce a highly generalizable, single-cell framework for the mechanism-based prioritization of drugs to treat rare, highly heterogeneous tumors. Analysis of transformed cells, accounting for only 10% of a cholangiocarcinoma patient biopsy revealed three molecularly-distinct subpopulations, predicted to be sensitive to four drugs by regulatory network-based analysis. Validation in a low-passage, patient-derived xenograft (PDX) from the same patient confirmed tumor growth rate control by two of these drugs (plicamycin and dacinostat) and further validated predicted subpopulation-specific effects, suggesting they may represent promising candidates for follow-up clinical trials, either alone or in combination with current standard-of-care chemotherapies. The proposed approach can be generalized to elucidate complementary dependencies of rare, heterogeneous tumors, at the single cell level.

cancer biology↗

bioRxiv2020

Type-1 IFN primed monocytes in pathogenesis of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most severe form of lung fibrosis. It is progressive, and has an extremely poor outcome and limited treatment options. The disease exclusively affects the lungs, and thus less attention has been focused on blood-borne immune cells. which could be a more effective therapeutic target than lung-based cells. Here, we questioned if circulating monocytes, which has been shown to be increased in IPF, bore abnormalities that might contribute to its pathogenesis. We found that levels of circulating monocytes correlated directly with the extent of fibrosis in the lungs, and increased further during acute clinical deterioration. Monocytes in IPF were phenotypically distinct, displaying increased expression of CD64, a type 1 IFN gene expression signature and a greater magnitude of type 1 IFN response when stimulated. These abnormalities were accompanied by markedly raised CSF-1 levels in the serum, prolonged survival of monocytes ex vivo, and increased numbers of monocytes in lung tissue. Our study defines the key monocytic abnormalities in IPF, proposing type 1 IFN-primed monocytes as a potential driver of an aberrant repair response and fibrosis. It provides a rationale for targeting monocytes and identifies monocytic CD64 as a potential specific therapeutic target for IPF.

immunology↗