Biology subjects

Taha, H. B.

Publications and source records attributed to Taha, H. B..

5 recordsLinked to original sources

bioRxiv2025

Transcriptomic analysis of 40 human and rodent skeletal muscle exerkines

Animal and human studies show that exercise induces organism wide molecular adaptations, many of which are mediated by exerkines which are secreted factors that enable communication between tissues such as skeletal muscle, adipose tissue, liver and the brain. However, the tissue specific responsiveness of individual exerkines and how these responses differ across species, exercise conditions and sexes remain poorly understood. To address this gap, we systematically analyzed skeletal muscle transcriptomic responses of 40 exerkines using three publicly available datasets which include MetaMEx, Extrameta and the MoTrPAC rat training study. We analyzed exerkine specific regulation in humans, mice and rats across acute and chronic exercise as well as inactivity, and determined which responses were conserved, species specific, sex dependent or dependent on exercise duration. Our analysis reveals substantial heterogeneity in skeletal muscle exerkine regulation with only a small subset showing conserved changes across species, while many exerkines exhibited human exclusive, rodent exclusive, acute specific or chronic specific patterns. These results provide a ranked overview of the most exercise responsive skeletal muscle exerkines and highlight the need for multi species and multi condition approaches when selecting exerkines as biomarkers or therapeutic targets.

physiology↗

bioRxiv2025

NANOME: A Nextflow pipeline for haplotype-aware allele-specific consensus DNA methylation detection by nanopore long-read sequencing

Nanopore long-read sequencing has expanded the capacity of long-range, single-base, and single-molecule DNA-methylation (DNAme) detection and haplotype-aware allele-specific epigenetic phasing. Previously, we benchmarked and ranked the robustness of seven computational tools for DNAme detection using nanopore sequencing. The top performers were Megalodon, Nanopolish, DeepSignal and Guppy. However, these algorithms exhibit lower performance at regions with discordant non-singleton DNAme patterns compared to genome-wide regions. Furthermore, long-read sequencing analysis of mammalian genomes requires higher computational resources than next-generation sequencing. To address these issues, we developed a NANOpore Methylation (NANOME) a consensus DNAme predictive model using XGBoost, which integrates the output of Megalodon, Nanopolish, and Deepsignal for analyzing data obtained using Oxford Nanopore Technologies (ONT). NANOME enhanced DNAme detection precision (mean square error) at single-base resolution by 11% and improved accuracy (F1-score) at single-molecule resolution by 2.4% for human B-lymphocyte European cell lines (NA12878). The consensus model also detected [~]200,000 more CpGs than all three tools. Combing variant calling and long-read phasing, NANOME can detect haplotype-aware allele-specific DNAme in known imprinting controls in resolved and previously unresolved regions. We conducted haplotype-aware methylation detection on the T2T genome for dataset NA12878, revealing significant variations in differentially methylated region (DMR) density between gap and non-gap regions. Overall, NANOME represents a significant step forward in DNAme detection and long-range epigenetic phasing, offering a robust and accessible tool for researchers studying the epigenome.

bioinformatics↗

bioRxiv2024

Global multi-omics analysis of exerkines in progressive treadmill-exercised rodents

Exercise is widely recognized for its comprehensive physiological benefits, attributed largely to the secretion of signaling molecules known as exerkines. These molecules, originating from various tissues like muscles, brain, and liver, facilitate inter-organ communication and enhance metabolic health, immune function, and tissue repair. However, the responsiveness of multiple tissues and exerkines to the same exercise regimen remains poorly understood. To address this issue and elucidate patterns of time-dependent, intensity-related and sex-dimorphic tissue and exerkine responsiveness, we leveraged the publicly available Molecular Transducers of Physical Activity Consortium (MoTrPAC) dataset. Male and female Fischer 344 rats aged 6 months underwent a progressive treadmill training protocol designed to emulate human endurance exercise. Blood (cells and plasma) and 18 solid tissues such as adipose, skeletal muscle and brain were collected and multi-omics analyses, including proteomics and transcriptomics were performed on them. We examined the distribution of 26 known and 2 speculative exerkines across 2 biofluids and 18 solid tissues. Our analysis reveals that brown adipose tissue (BAT), the adrenal gland, and white adipose tissue (WAT) are the most responsive to exercise-induced changes. Fractalkine was the most responsive exerkine, followed by prosaposin (speculative), cathepsin B, and FNDC5/irisin, platelet factor 4, Clusterin and SPARC. Additionally, we found distinct patterns in the responsiveness of tissues and exerkines based on the duration and intensity of exercise, with notable differences between male and female rodents. Future research should investigate whether our findings on tissue exerkine responsiveness vary with age and disease status, and determine if these findings can be extrapolated to human populations.

physiology↗

bioRxiv2024

Activation of the muscle-to-brain axis ameliorates neurocognitive deficits in an Alzheimer disease mouse model via enhancing neurotrophic and synaptic signaling

INTRODUCTIONSkeletal muscle regulates central nervous system (CNS) function and health, activating the muscle-to-brain axis through the secretion of skeletal muscle originating factors ( myokines) with neuroprotective properties. However, the precise mechanisms underlying these benefits in the context of Alzheimers disease (AD) remain poorly understood. METHODSTo investigate muscle-to-brain axis signaling in response to amyloid {beta} (A{beta})- induced toxicity, we generated 5xFAD transgenic female mice with enhanced skeletal muscle function (5xFAD;cTFEB;HSACre) at prodromal (4-months old) and late (8-months old) symptomatic stages. RESULTSSkeletal muscle TFEB overexpression reduced A{beta} plaque accumulation in the cortex and hippocampus at both ages and rescued behavioral neurocognitive deficits in 8- months-old 5xFAD mice. These changes were associated with transcriptional and protein remodeling of neurotrophic signaling and synaptic integrity, partially due to the CNS-targeting myokine prosaposin (PSAP). DISCUSSIONOur findings implicate the muscle-to-brain axis as a novel neuroprotective pathway against amyloid pathogenesis in AD.

neuroscience↗

bioRxiv2024

Validating an Immunoassay to Measure Fecal Glucocorticoid Metabolites in Yellow-Bellied Marmots

The yellow-bellied marmot (Marmota flaviventer) study at the Rocky Mountain Biological Laboratory near Crested Butte, Colorado, USA is the worlds second longest study of free-living mammals. Quantifying physiological stress is essential for understanding their health, reproductive success, and survival in a variable environment. Historically, we used a validated radioimmunoassay (RIA) to measure fecal glucocorticoid metabolites (FGMs). Given the costs and risks of working with radioisotopes, we have shifted to a more sustainable method. Here we evaluate the suitability of two competitive enzyme-linked immunosorbent assays (ELISA) from Cayman Chemical Company (CCC) and Arbor Assays (AA) to measure corticosterone levels in FGMs. The findings revealed that the AA ELISA, unlike the CCC ELISA, consistently matched the RIA in terms of accuracy across high and low corticosterone concentrations, demonstrated superior assay parameters, showed the highest correlations with RIA results and effectively captured the annual variations in FGM concentrations, indicative of its reliability for use in longitudinal studies. We further analytically validated the usage of the AA ELISA for FGMs, confirming its efficacy without matrix effects, thus establishing its suitability for ongoing and future studies of FGMs in marmots. The transition to the AA ELISA from the RIA ensures continued data integrity while enhancing safety and environmental sustainability.

physiology↗