Biology subjects

Gill, S. E.

Publications and source records attributed to Gill, S. E..

3 recordsLinked to original sources

bioRxiv2026

Early sex-specific organ transcriptional divergence without physiological differences in a murine model of fecal-induced peritonitis

Sepsis is defined as a dysregulated response to infection, leading to life-threatening organ dysfunction that particularly affects parenchymal organs. Clinical studies remain inconclusive regarding the impact of biological sex on sepsis, and preclinical studies are predominantly performed in male animals. We examined early (8 h) septic responses in male and female mice using a fecal-induced peritonitis (FIP) model. Blood biochemical parameters, body temperature, and murine sepsis scores provided evidence of a septic response in animals randomized to FIP compared to controls, but showed no physiological differences between male and female mice. Transcriptomic analysis of the liver, kidney, and lung showed consistent inflammatory activation in response to sepsis as compared to controls. Notably, in the kidney and lung, female mice exhibited stronger immune activation and a heightened inflammatory response compared to males. Thus, biological sex differences in the septic response can be detected in early acute sepsis without apparent physiological differences.

pathology↗

bioRxiv2025

Artificial Intelligence-enabled Histological Analysis in Preclinical Respiratory Disease Models: A Scoping Review

Histological analysis is a cornerstone of preclinical respiratory disease research, enabling assessment of pathology, therapeutic effects, and mechanisms. However, conventional approaches rely on manual scoring, which is subjective, time-consuming, and difficult to scale due to low throughput and inter-observer variability. Artificial intelligence (AI), particularly deep learning, offers potential to automate histology workflows, but its use and evaluation in preclinical respiratory models have not been synthesized. We conducted a scoping review following Joanna Briggs Institute guidelines, searching MEDLINE and Embase (inception-January 2025) for preclinical studies using AI to analyze histology in respiratory disease models. Screening, full-text review, and data extraction were performed in duplicate. Of 6271 studies screened, 29 met inclusion criteria. Most used murine models (76%) and investigated lung cancer (28%), pulmonary fibrosis (24%), or tuberculosis (17%). Hematoxylin and eosin was the most common stain (48%), with others targeting collagen or immune markers. AI tasks included image classification (n=20), segmentation (n=10), and object detection (n=4), predominantly using convolutional neural networks (69%). Preprocessing methods (e.g., stain normalization) were common, but annotation and training practices were inconsistently reported. Performance was generally high (accuracy [≥]90%; 7 studies) though validation metrics varied, and external validation was absent. Most studies used "black box" models, with minimal application of explainability techniques. Reproducibility measures, such as sharing datasets or code were rarely reported. AI tools are poised to transform histological analysis in preclinical respiratory research. By addressing gaps in validation, transparency, and standardization, the field can harness these technologies to deliver robust, efficient, and scalable workflows. Registration: Open Science Framework https://doi.org/10.17605/OSF.IO/NM94E

cell biology↗

bioRxiv2025

The role of aging on endothelial cell-cell junctions and pulmonary microvascular permeability

Lung injury leads to pulmonary microvascular endothelial cell (PMVEC) damage, disruption of cell-cell junctions, and increased permeability. Previously, we demonstrated in a mechanical ventilation-induced model of lung injury that aging exacerbated pulmonary microvascular permeability. Based on this, we hypothesized that aging was associated with increased PMVEC barrier dysfunction due to impaired cell-cell junction integrity. PMVEC were isolated from young and aged mice and cultured to confluence in vitro. Barrier function and cell-cell junction integrity were assessed through electric cell-substrate impedance sensing, XPerT permeability assay, immunofluorescence, and western blot analysis. Further studies were conducted to examine alterations in the proteome, markers of inflammation, and actin cytoskeleton organization. To model injurious conditions, PMVEC were stimulated with inflammatory cytokines; permeability and actin cytoskeletal alterations were subsequently assessed. We observed increased basal permeability in PMVEC from aged mice, which was associated with disrupted cell-surface localization of the adherens junction protein, vascular endothelial (VE)-cadherin. Protein abundance of VE-cadherin was significantly increased with age; however, levels of the adapter protein,{gamma} -catenin, and the tight junction protein, claudin-5, were decreased. Measures of inflammation, including cytokine expression and cell surface abundance of adhesion molecules, did not differ with age. Alterations in actin cytoskeleton organization, characterized by augmented presence of actin stress fibers, were observed in aged PMVEC. Under inflammatory conditions, permeability and actin stress fiber formation were exacerbated with age. It is concluded that aging predisposes PMVEC to elevated injury, due to inherent deficiencies in cell-cell junctions and barrier function, potentially mediated through altered actin cytoskeleton organization. New and NoteworthyCompared with pulmonary microvascular endothelial cells (PMVEC) from young mice, PMVEC isolated from aged mice had higher permeability, which was directly associated with impairments in cell-cell junctions. The higher permeability in aged PMVEC was not associated with augmented inflammatory signaling but was associated with actin cytoskeletal alterations. Following an inflammatory insult, PMVEC from aged mice had further exacerbated permeability. These findings may begin to highlight why older patients exhibit higher mortality during lung injury.

cell biology↗