Biology subjects

Venosa, A.

Publications and source records attributed to Venosa, A..

4 recordsLinked to original sources

bioRxiv2026

Convergent Mitochondrial and Oxidative Stress Signatures in Spaceflight and Tauopathy: A Comparative Multi-Omics Reanalysis in Drosophila melanogaster

Mitochondrial dysfunction is a shared biological thread between terrestrial Alzheimer's disease (AD) and in the unique stress environment of spaceflight, making mitochondrial pathophysiology a compelling target for comparative investigation. In AD, mitochondrial impairment is closely linked to defective oxidative phosphorylation, reactive oxygen species accumulation, calcium dysregulation, and neuronal injury, while spaceflight stressors such as microgravity and radiation disrupt mitochondrial homeostasis and increase oxidative stress. Understanding how the extreme stressors of spacelight affect mitochondrial function may provide insights into conserved mitochondrial stress responses and their implications for neurodegenerative diseases, including AD. Our study compares datasets from ground control Drosophila melanogaster RNA-seq with isolated radiation and microgravity exposure to discern conserved mitochondrial pathways and molecular signatures that may provide insights into AD mechanisms.

cell biology↗

bioRxiv2024

Tenascin-C in the early lung cancer tumor microenvironment promotes progression through integrin activation and FAK

Pre-cancerous lung lesions are commonly initiated by activating mutations in the RAS pathway, but do not transition to lung adenocarcinomas (LUAD) without additional oncogenic signals. Here, we show that expression of the extracellular matrix protein Tenascin-C (TNC) is increased in and promotes the earliest stages of LUAD development in oncogenic KRAS-driven lung cancer mouse models and in human LUAD. TNC is initially expressed by fibroblasts and its expression extends to tumor cells as the tumor becomes invasive. Genetic deletion of TNC in the mouse models reduces early tumor burden and high-grade pathology and diminishes tumor cell proliferation, invasion, and focal adhesion kinase (FAK) activity. TNC stimulates cultured LUAD tumor cell proliferation and migration through engagement of v-containing integrins and subsequent FAK activation. Intringuingly, lung injury causes sustained TNC accumulation in mouse lungs, suggesting injury can induce additional TNC signaling for early tumor cell transition to invasive LUAD. Biospecimens from patients with stage I/II LUAD show TNC in regions of FAK activation and an association of TNC with tumor recurrence after primary tumor resection. These results suggest that exogenous insults that elevate TNC in the lung parenchyma interact with tumor-initiating mutations to drive early LUAD progression and local recurrence.

cancer biology↗

bioRxiv2022

Breathing dysfunction and alveolar damage in a mouse model of Dravet syndrome

ObjectiveThe incidence of Sudden Unexpected Death in Epilepsy (SUDEP) is especially high in those with Dravet syndrome (DS). Risk factors have been identified, but the mechanism(s) by which death occurs is not fully understood. Evidence supports ventilatory dysfunction in the pathophysiology of SUDEP. Understanding specific respiratory patterns present at baseline and after seizures at different ages, as well as the health of lung tissue, will allow us to better understand how sudden death occurs in this population. MethodsWhole body plethysmography (WBP) was used to monitor respiration before and after electrically induced seizure in the Scn1aA1783V/WT mouse model of DS weekly for a period of four weeks. Following the four-week WBP study, lungs from surviving animals were collected and stained with hematoxylin and eosin and Weigerts elastin and the density of tissue and elastin were analyzed. ResultsBreathing was diminished in the DS mouse at baseline and following evoked seizures in younger aged mice (P18-P24), consistent with prolonged post-ictal inspiratory time and low respiratory drive compared to the response seen in older animals. In older DS mice, consisting of those that have survived a critical period for mortality, the response to seizure was more robust and included higher respiratory drive, peak inspiratory and expiratory flow rates, tidal and expiratory volumes, and breathing frequency compared to wild-type and relative to baseline. Alveolar damage was also observed in P46-P52 DS mice. SignificanceDifferences in specific respiratory parameters in younger DS animals, during the time when mortality is greatest, compared to older DS animals (i.e. those that have survived the critical period) may allow us to better understand respiratory differences contributing to SUDEP. Lung tissue damage in DS may also contribute to respiratory dysfunction in SUDEP. KEY POINTSO_LIBaseline respiration is diminished in DS mice compared to wild type. C_LIO_LIElectrically induced seizure produced a different respiratory response in younger DS mouse compared to older DS animals. C_LIO_LIAlveolar septal damage is present in DS mice. C_LIO_LIBaseline and post-ictal breathing dysfunction and inefficient oxygenation and CO2 clearance likely potentiated by lung damage may serve as a potential mechanism by which SUDEP occurs in DS. C_LI

physiology↗

bioRxiv2021

Red Blood Cells Function as DNA Sensors

Erythrocytes have long been mistaken as exclusively inert oxygen carriers lacking immune function. Here we show that red blood cells (RBCs) serve as immune sensors through surface expression of the nucleic acid-sensing toll-like receptor 9 (TLR9), a classically endosomal receptor that initiates immune responses following the detection of unmethylated CpG motifs present in pathogen and mitochondrial DNA. Mammalian RBCs express TLR9 on their surface and bind CpG-containing bacterial, malarial, and mitochondrial DNA. Erythrocyte-bound CpG DNA increases during infection, and CpG-carrying RBCs trigger accelerated erythrophagocytosis and innate immune activation characterized by RBC-TLR9 dependent local and systemic cytokine production. Thus, RBC nucleic acid detection and capture regulates red cell clearance and immune responses and provides evidence for RBCs as innate immune sentinels during pathologic states. One Sentence SummaryThe ability of RBCs to detect and bind cell-free nucleic acids contributes to immunity during acute inflammatory states.

immunology↗