Biology subjects

Oakes, J. M.

Publications and source records attributed to Oakes, J. M..

5 recordsLinked to original sources

bioRxiv2026

Structural Lung Remodeling Precedes Functional Decline After Chronic Smoldering Douglas Fir Smoke Exposure in Apoe-/- Mice

Wildland firefighters experience repeated exposure to wildfire smoke, yet the pathophysiological mechanisms underlying chronic inhalation injury remain poorly understood. Although prior studies report parenchymal destruction following prolonged woodsmoke exposure, the temporal relationship between molecular, structural, and functional decline following inhalation of smoke from needles/leaves remains unclear. To address this gap, we characterized coordinated changes in lung structure, function, and underlying molecular disruptions using a dosimetry-based murine model approximating 7-14 years of firefighter service. Male apolipoprotein E-deficient mice were exposed to smoldering Douglas fir needle smoke (40 mg/m3, 2 h/day, 5 days/week) for 8 or 16 weeks. Immunofluorescence analyses revealed an early elastolytic response at 8 weeks, with increased neutrophil elastases and matrix metalloproteinases-9 and -12, accompanied by elevated surfactant protein-D, compared to air controls. These changes were resolved by 16 weeks despite progressive tissue injury. Airspace enlargement was evident at 8 weeks, progressed by 16 weeks, and included increased alveolar blunting and septal wall thickening at the later time point. Cleaved caspase-3 was elevated at 16 weeks, indicative of advanced parenchymal damage and apoptosis. Epithelial tight-junction protein ZO-1 intensity was reduced at both evaluation points, whereas the epithelial-to-mesenchymal marker N-cadherin remained undetectable in the alveolar epithelium. Functional impairment as evident by increased static compliance and upward shifts in pressure-volume curves was only significant after 16 weeks of exposure. Findings indicate that molecular and structural injury of tissue destruction preceded measurable functional decline, underscoring the need for early biomarkers to identify smoke-induced lung injury in wildland firefighters before function loss occurs.

physiology↗

bioRxiv2025

Adaptive-like NK cell responses to influenza correlate with humoral immunity and are influenced by age and sex

Influenza remains a global health threat, infecting approximately one billion people annually and causing significant mortality, particularly among older adults. While hemagglutination inhibition (HAI) antibody titers are a standard correlate of immunity against influenza, they do not reliably predict protection in high-risk populations. Using multiomic single-cell profiling, we identified a distinct subset of adaptive-like NK cells that respond to influenza antigen, predominantly in younger females. These TNFSF10+LGALS9+ NK cells exhibit features of adaptive NK cells but lack classical cytomegalovirus-driven markers observed in previous studies. Notably, their increased frequency correlates with high pre-existing HAI titers, suggesting a link between adaptive-like NK responses and humoral immunity. Together, our findings identify an NK subset influenced by age and sex that may contribute to influenza protection, expanding the known diversity of adaptive-like NK cells. These insights could inform future vaccine strategies, particularly for aging populations, by integrating NK responses into assessments of vaccine efficacy.

immunology↗

bioRxiv2025

Antiviral CD4+ T and myeloid cell responses to influenza vaccines are attenuated in older adults

Recent influenza vaccine formulations have improved the magnitude of B-cell antibody responses in older adults; however, older adults remain significantly at risk for severe influenza-related illness. Although antibodies are an important metric of vaccine effectiveness, they only represent one aspect of the immune response. In this study, we combined in vitro and ex vivo assays with human samples to investigate B, CD4+ T, and myeloid cell responses to influenza vaccine antigens. We found that older adults mounted equivalent antibody titers to younger adults but had fewer influenza-specific CD4+ T cells and reduced antiviral-associated T helper cell populations. Single-cell transcriptomics revealed that older adults had attenuated interferon transcriptional signatures in T helper and myeloid cell subsets. These data suggest that with aging, transcriptional programming alterations in myeloid cells contribute to reduced antiviral T cell responses, and formulating vaccines tailored to myeloid responses is necessary to improve outcomes in older adults.

immunology↗

bioRxiv2024

Co-Therapy with S1P and Heparan Sulfate Derivatives to Restore Endothelial Glycocalyx and Combat Pro-Atherosclerotic Endothelial Dysfunction

Endothelial cell (EC) glycocalyx (GCX) shedding due to disturbed blood flow and chemical factors leads to low-density lipoprotein infiltration and reduced nitric oxide synthesis, causing vascular dysfunction and atherosclerosis. This study evaluates a novel therapy combining sphingosine-1-phosphate (S1P) and heparin (heparan sulfate derivative). We hypothesized that heparin/S1P would repair mechanically damaged EC GCX in disturbed flow (DF) regions and restore anti-atherosclerotic mechanotransduction function, addressing cardiovascular disease. We used a parallel-plate flow chamber to simulate flow conditions in vitro and a partial carotid ligation mouse model to mimic DF in vivo. Heparin and albumin-bound S1P were administered to assess their reparative effects on the endothelial GCX. Immunocytochemistry, fluorescent staining, confocal microscopy, cellular alignment studies, and ultrasound were performed to evaluate EC function and endothelial-dependent vascular function. Barrier functionality was assessed via macrophage uptake. Heparin/S1P mechanism-of-action insights were gained through fluid dynamics simulations and staining of GCX synthesis enzyme as well as S1P receptor. Statistical analyses validated results. In vitro data showed that heparin/S1P therapy improves the function of DF-conditioned ECs by restoring EC GCX and promoting EC alignment and elevated vasodilator eNOS (endothelial-type nitric oxide synthase) expression. The in vivo studies confirmed GCX degradation, increased vessel inflammation and hyperpermeability, and vessel wall thickening in the partially ligated left carotid artery. Heparin/S1P treatment restored GCX in the left carotid artery, enhancing GCX thickness and coverage of the blood vessel wall. This work advances a new approach to regenerating the EC GCX and restoring its function in ECs under DF conditions.

bioengineering↗

bioRxiv2023

Hot spots drive uptake and short-term processing of organic and inorganic carbon and nitrogen in intertidal sediments

This study uses dual-labelled (13C and 15N) stable isotope applications to examine uptake and short-term processing of carbon (C) and nitrogen (N) by microbial communities in intertidal sediment from three subtropical estuarine sites. We examine differences in microbial uptake and retention that arise due to domination of microbial processing by either microphytobenthos or heterotrophic bacteria. We compare amino acids and algal dissolved organic matter (Algal DOM) and glucose and NH4+ versus newly fixed microphytobenthos C (MPB-C) and NH4+ using in situ applications across 24 h to identify uptake into the microbial community and sediment OM. Algal DOM had preferential C uptake and more retention across 24 h indicating precursors incorporated into biosynthetic pathways for biomass. Conversely, amino acid C was not incorporated or rapidly respired to DIC but displayed clear preferential uptake and retention of 15N. Short-term (24 h) retention of glucose was higher than MPB-C, while uptake of 15N from NH4+ was similar between treatments, potentially indicating glucose-stimulated export of 15N via coupled nitrification-dentrification. Despite careful selection of similar sites and sediment types, we found substantial variability between replicates and sites in the uptake and processing of labeled substrate that challenged traditional statistical analysis due to non-homogenous variance. Uptake variability across orders of magnitude is likely due to disproportionate processing of substrates occurring in hotspots of microbial processing within sediment. Development of analytical techniques to provide robust strategies to handle variability caused by abiotic and biotic factors will allow greater clarity surrounding in situ biogeochemical processing in intertidal environments.

ecology↗