bioRxiv Science⌕ Search

Biology subjects

Eom, M.

Publications and source records attributed to Eom, M..

5 recordsLinked to original sources

Multilevel Regulation of Skeletal Muscle Ferroptosis in Aging: Sex- and Exercise-Dependent Effects on Histological, Molecular, and Genetic Markers

BackgroundFerroptosis, an iron-dependent form of regulated cell death, is increasingly recognized as a key contributor to aging-associated skeletal muscle degeneration and dysfunction. However, the interactive effects of aging, sex, and exercise modality on ferroptosis regulatory markers at the histological, protein, and gene expression levels remain poorly understood. MethodsMale (n = 23) and female (n = 23) mice aged 7 (young) and 17 (aged) months were assigned to sedentary control, voluntary wheel running, or forced treadmill exercise. Ferroptosis in the quadriceps muscle was assessed using histological markers (e.g., fibrosis, Fe3 accumulation, 4-HNE, MDA), protein-level markers (e.g., GPX4, SLC7A11, p-AMPK, MDA, GSH/GSSG), and gene expression markers (e.g., SLC7A11, GSS, ACSL4, POR). ResultsAging significantly elevated histological indicators of ferroptosis--fibrosis, lipid peroxidation, and iron overload--regardless of sex. At the protein and gene levels, sex-dependent differences were evident: aged females exhibited lower MDA and GSSG levels and upregulation of antioxidant-related genes, compared with aged males. Both exercise interventions modulated ferroptosis markers, with forced exercise exerting more pronounced effects than voluntary exercise. Notably, aged females demonstrated the most substantial reductions in ferroptosis-related markers in response to forced exercise, indicating a significant sex-by-exercise interaction. ConclusionAging markedly increases ferroptosis-related changes in skeletal muscle, with partial sex-specific differences at the molecular level. Forced exercise provides more robust regulatory effect against ferroptosis than voluntary exercise, especially in aged females. These findings underscore the therapeutic potential of sex-specific, targeted exercise interventions for mitigating ferroptosis-mediated muscle deterioration during aging.

physiology↗

Bright and Photostable Voltage Sensors Derived from mBaoJin

Genetically encoded voltage indicators (GEVIs) are powerful tools for monitoring neuronal activity, but their application, particularly for long-term recordings in vivo, is often limited by photobleaching under the required high illumination intensities. This constraint restricts the total duration of continuous or trial-based experiments, crucial for studying processes like synaptic plasticity or circuit dynamics during behavior. Here, we introduce ElectraON and ElectraOFF, a pair of green fluorescent eFRET-based GEVIs engineered by incorporating a photostability-enhanced derivative of the bright monomeric fluorescent protein mBaoJin with Ace opsin variants. Critically, Electras demonstrate over 6-fold improved photostability compared to state-of-the-art eFRET GEVIs, pAce, and Ace-mNeon2, under one-photon illumination, while characterized by bright green fluorescence, millisecond kinetics, and good membrane localization. This enhanced stability translates to a 3-to >10-fold extension in functional recording duration, maintaining reliable spike detection in both cultured neurons in vitro and sparsely labeled neurons in the awake mouse cortex in vivo. We demonstrated sustained in vivo recordings exceeding 30 minutes, with instances surpassing one hour. Furthermore, Electras show functionality under scanless two-photon excitation in cultured cells. These highly photostable indicators significantly extend the temporal window for voltage imaging, broadening the scope of accessible biological questions.

neuroscience↗

A Sensitive Soma-localized Red Fluorescent Calcium Indicator for Multi-Modality Imaging of Neuronal Populations In Vivo

Recent advancements in genetically encoded calcium indicators, particularly those based on green fluorescent proteins, have optimized their performance for monitoring neuronal activities in a variety of model organisms. However, progress in developing red-shifted GECIs, despite their advantages over green indicators, has been slower, resulting in fewer options for end-users. In this study, we explored topological inversion and soma-targeting strategies, which are complementary to conventional mutagenesis, to re-engineer a red genetically encoded calcium indicator, FRCaMP, for enhanced in vivo performance. The resulting sensors, FRCaMPi and soma-targeted FRCaMPi (SomaFRCaMPi), exhibit up to 2-fold higher dynamic range and peak {Delta}F/F0 per single AP compared to widely used jRGECO1a in neurons in culture and in vivo. Compared to jRGECO1a and FRCaMPi, SomaFRCaMPi reduces erroneous correlation of neuronal activity in the brains of mice and zebrafish by two- to four-fold due to diminished neuropil contamination without compromising the signal-to-noise ratio. Under wide-field imaging in primary somatosensory and visual cortex in mice with high labeling density (80-90%), SomaFRCaMPi exhibits up to 40% higher SNR and decreased artifactual correlation across neurons. Altogether, SomaFRCaMPi improves the accuracy and scale of neuronal activity imaging at single-neuron resolution in densely labeled brain tissues due to a 2-3-fold enhanced automated neuronal segmentation, 50% higher fraction of responsive cells, up to 2-fold higher SNR compared to jRGECO1a. Our findings highlight the potential of SomaFRCaMPi, comparable to the most sensitive soma-targeted GCaMP, for precise spatial recording of neuronal populations using popular imaging modalities in model organisms such as zebrafish and mice.

neuroscience↗

In Vivo Optical Clearing of Mammalian Brain

Established methods for imaging the living mammalian brain have, to date, taken the brains optical properties as fixed; we here demonstrate that it is possible to modify the optical properties of the brain itself to significantly enhance at-depth imaging while preserving native physiology. Using a small amount of any of several biocompatible materials to raise the refractive index of solutions superfusing the brain prior to imaging, we could increase several-fold the signals from the deepest cells normally visible and, under both one-photon and two-photon imaging, visualize cells previously too dim to see. The enhancement was observed for both anatomical and functional fluorescent reporters across a broad range of emission wavelengths. Importantly, visual tuning properties of cortical neurons in awake mice, and electrophysiological properties of neurons assessed ex vivo, were not altered by this procedure.

bioengineering↗

Statistically unbiased prediction enables accurate denoising of voltage imaging data

Here we report SUPPORT (Statistically Unbiased Prediction utilizing sPatiOtempoRal information in imaging daTa), a self-supervised learning method for removing Poisson-Gaussian noise in voltage imaging data. SUPPORT is based on the insight that a pixel value in voltage imaging data is highly dependent on its spatially neighboring pixels in the same time frame, even when its temporally adjacent frames do not provide useful information for statistical prediction. Such spatiotemporal dependency is captured and utilized to accurately denoise voltage imaging data in which the existence of the action potential in a time frame cannot be inferred by the information in other frames. Through simulation and experiments, we show that SUPPORT enables precise denoising of voltage imaging data while preserving the underlying dynamics in the scene.

neuroscience↗