Biology subjects

Matt, A.

Publications and source records attributed to Matt, A..

3 recordsLinked to original sources

bioRxiv2026

Drosophila melanogaster Nepl15 regulates lifespan, motor function, aging, heart rate, and cellular health in a sex-specific manner

Aging and obesity are characterized by comorbidities like declines in fertility, lifespan, gut barrier integrity, cardiac function, and motor activity, and an increase in oxidative stress due to altered nutrient and energy homeostasis. A study on Drosophila Neprilysin-like 15 (Nepl15) demonstrated that loss of Nepl15 gene significantly reduced glycogen and glycerolipid reserves in adult males and increased glycogen storage in adult females despite similar food consumption as controls. Therefore, we investigated the sex- and age-specific consequences of Nepl15 loss on cellular and physiological parameters associated with aging and obesity. We observed that egg production, rate of pupariation, and rate of adult fly eclosion were slightly better in the mutant flies. Interestingly, mutant females, but not males, exhibited significantly extended lifespan. Both sexes demonstrated improved locomotor performance, exercise endurance, gut barrier integrity, and preserved heart rate during progressive aging. At the cellular level, female mutants displayed reduced oxidative stress, elevated Sod2 expression, and increased ATP levels, all indicative of enhanced cellular health. Mutant males exhibited an increased mitochondrial membrane potential, indicating an enhanced capacity for rapid ATP production in response to enforced activity. Consistently, the energy-sensing kinase AMPK expression was reduced in the mutants. The lifespan extension of mutant females was supported by downregulation of mTOR and upregulation of Sirt6 expression. However, in mutant males, both mTOR and Sirt6 were downregulated, potentially contributing to improved physiological health without changing their lifespan. Collectively, our findings establish Nepl15 knockout mutation promotes anti-aging and anti-obesity health benefits, with stronger effects in female flies.

cell biology↗

bioRxiv2025

Drosophila melanogaster model of RVCL-S demonstrates age dependent disease progression

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a disease that causes deterioration of small vessels, affecting various organs: eyes, brain, liver, and others. The RVCL-S carriers have lower life expectancy. There is no cure available to date. The disease has been linked to mutations in TREX1 gene disrupting its cytoplasmic localization. To facilitate the disease mechanism investigation, we employed model organism D. melanogaster, identified human TREX1 ortholog cg3165, and confirmed its vital significance to flies. Then, we expressed human TREX1 and its mutant form TREX1 V235Gfs in flies and used optical coherence microscopy (OCM) to monitor the dynamics of flies vascular system. We detected the relapse of fly dorsal vessel, movement impairment, and reduced longevity in TREX1 V235Gfs-expressing transgenic animals. Vascular deterioration and shorter life span recapitulate the RVCL-S manifestations in humans. We have established a robust quantitative Drosophila RVCL-S phenotypic system that can potentially serve as a screening platform for drug discovery and drug targets identification.

genetics↗

bioRxiv2025

Application of Spectral Domain Optical Coherence Tomography To Guide Cochlear Implant Electrode Array

HypothesisA custom spectral domain optical coherence tomography (SD-OCT) platform can be used for real-time guidance of a cochlear implant electrode array (EA). BackgroundWith current cochlear implant surgical techniques, placement of the EA is a blind maneuver in which the surgeon relies on tactile feedback as the EA advances through the cochlear lumen. Cochlear implant trauma is a leading factor for poor speech performance outcomes and loss of residual hearing following surgery. Optical coherence tomography (OCT) is a non-invasive imaging modality that provides real-time visualization of tissue microstructure at higher spatial resolutions compared to clinical CT and MRI. Already adopted as standard of care in ophthalmology, OCT has the potential to assist the surgeon in real-time visualization of the EA trajectory. Unlike commercial systems, our custom OCT system allows tailored wavelength, scanning geometry, and real-time processing, which are critical factors for navigating the compact anatomy of the facial recess to image the cochlea. MethodsA custom-built SD-OCT system was used to image cochlear microanatomy in mice and human cadaveric temporal bones. The OCT system was then used to guide a mock EA in human cadaveric temporal bones in real-time using individual B scans that were reviewed sequentially as the EA was being advanced through the round window. ResultsUsing our OCT system, high-resolution (< 5.0 m) images of cochlear microanatomy were obtained in both mice and cadaveric human temporal bones with an image sensitivity of [~]104 dB. Following cochleostomy in cadaveric temporal bones, real-time sequential OCT B-scans were used to reliably guide placement of the EA through the scala tympani. ConclusionOur custom-built SD-OCT platform can generate high-resolution real-time visualization and orientation of mammalian cochlear microanatomy that can be used to assist with real time guidance of a CI EA. This technology has the potential to serve as a real-time surgical image guidance tool to minimize EA trauma and further our understanding of human cochlear pathophysiology.

bioengineering↗