Jayachandran, C. | bioRxiv Science

bioRxiv2025

Upper Airway Gene Expression in Hospitalized Children with Rhinovirus-induced Respiratory Illnesses

BackgroundThe precise mechanisms underlying rhinovirus (RV)-induced respiratory illnesses are not completely known. ObjectiveWe sought to obtain nasal transcriptomic data from hospitalized children with respiratory viral infections. MethodsWe obtained nasal swabs from 46 children with RV (16 RV-A, 30 RV-C). For comparison, we examined swabs from 12 children with RSV and six controls. Subjects ranged in age from 1 month to 18 years. Viral detection, genotyping and copy number were determined by PCR. RNA transcripts were measured by next generation sequencing and differences in gene expression calculated using DESeq2. ResultsCompared to controls, 1232 transcripts were upregulated (adjusted p<0.05, fold change >1.5) by all three viruses, including genes regulating granulocyte chemotaxis, cysteinyl leukotriene production, epithelial remodeling and antiviral responses. Cilium-related genes were downregulated. Compared to RSV, RV induced greater expression of 207 genes including those regulating eosinophilic inflammation, mucus secretion and mast cell function.RSV induced greater upregulation of 674 genes including those regulating neutrophilic inflammation and type 1 IFN response. Computational deconvolution of RNA-seq profiles revealed that viral infection decreased ciliated cells while increasing neutrophils, natural killer cells, monocytes (all viral species) and goblet cells (RV only). RV-C infections increased mast cells and IFN-{lambda} mRNA expression. RV copy number correlated with the expression of mast cell proteases and numerous pro-inflammatory and IFN-stimulated genes. ConclusionChildren hospitalized with RV and RSV infections mount robust inflammatory responses, but virus-specific differences exist. Clinical ImplicationThese data provide insight into mechanisms by which RV, and in particular, RV-C, trigger respiratory illnesses. Capsule summaryNasal transcriptomics demonstrate that RV infections in hospitalized children induce expression of genes regulating eosinophilic inflammation, mucus secretion and mast cell function, with RV-C in particular increasing IFN-{lambda} expression.

immunology↗

bioRxiv2021

A DNA-based optical force sensor for live-cell applications

Mechanical forces are relevant for many biological processes, from wound healing or tumour formation to cell migration and differentiation. Cytoskeletal actin is largely responsible for responding to forces and transmitting them in cells, while also maintaining cell shape and integrity. Here, we describe a novel approach to employ a FRET-based DNA force sensor in vitro and in cellulo for non-invasive optical monitoring of intracellular mechanical forces. We use fluorescence lifetime imaging to determine the FRET efficiency of the sensor, which makes the measurement robust against intensity variations. We demonstrate the applicability of the sensor by monitoring cross-linking activity in in vitro actin networks by bulk rheology and confocal microscopy. We further demonstrate that the sensor readily attaches to stress fibers in living cells which opens up the possibility of live-cell force measurements.

biophysics↗