Curras-Tuala, M. J. | Search bioRxiv

bioRxiv2026

A prospective multi-cohort study identifies reproducible molecular responses to musical stimulation in the human tear proteome

Music elicits complex emotional, cognitive, and physiological responses, yet the molecular mechanisms underlying these effects remain poorly understood. Tear fluid is an accessible biofluid that reflects both systemic and local physiology, providing a unique opportunity to investigate the biological effects of musical stimulation. Quantitative mass spectrometry-based proteomics was performed on paired tear samples (n = 336) collected before and after exposure to a standardized musical stimulus in two independent cohorts of healthy participants, including both music-stimulated and music-unstimulated individuals. Integrative analyses, including differential expression, functional enrichment, co-expression network, correlation, and machine-learning approaches, identified reproducible molecular responses across cohorts. Fourteen proteins, including PRTN3, LEG3, CATD, IGHG2, and ZA2G, remained significant after multiple-testing correction and showed concordant regulation in the stimulated cohorts but not in controls. Functional enrichment converged on innate immune, inflammatory, host-defense, and extracellular signaling pathways, and consensus network analysis identified reproducible immune-related modules. The 14-protein signature robustly discriminated pre- and post-stimulation samples, with no effect detected in the unstimulated control groups. These findings support tear proteomics as a promising non-invasive approach for investigating the molecular basis of auditory and emotional experiences.

molecular biology↗

bioRxiv2021

A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity

BackgroundCOVID-19 symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. Methods and findingsWe carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. We then used a differential expression approach and pathways analysis to detect tissue specific immune severity signals in COVID-19 patients. Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were shown in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis. ConclusionsWe found severity-related signatures in patient tissues mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy.

genomics↗