Biology subjects

Mahdaviani, K.

Publications and source records attributed to Mahdaviani, K..

7 recordsLinked to original sources

bioRxiv2026

The tilt board task as an internally valid practice-transfer paradigm for stabilometer balance assessments

Practice-transfer paradigms are central to motor learning research, yet dynamic balance lacks standardized, internally valid practice-transfer task pairings. This study evaluated whether a mediolateral tilt board can serve as a valid transfer task for stabilometer-based balance assessment. Sixteen healthy young adults (20-35 years) completed a single session consisting of two 40-second trials on a mediolateral stabilometer and two 40-second trials on a mediolateral tilt board. Participants aimed to keep each platform horizontal during each trial. Performance outcomes were derived from platform deviation angle. Neuromuscular outcomes were derived from surface EMG of bilateral gluteus medius, vastus lateralis, and vastus medialis, including muscle synergy structure, bilateral co-activation index, RMS amplitude of muscle activation, and strategy ratios (hip-to-knee and asymmetry metrics). Between-task associations were assessed using Spearman correlations. Cross-task muscle synergy similarity was high (mean cosine similarity = 0.915 {+/-} 0.044) and close to within-task trial-to-trial similarity, indicating preserved modular coordination across devices. Performance metrics were moderately to strongly correlated between tasks (RMS deviation angle: {rho} = 0.621, p = 0.0089; time-in-balance: {rho} = 0.668, p = 0.0036). EMG-derived strategy metrics also correlated significantly across tasks, including bilateral co-activation ({rho} = 0.688, p = 0.0023), hip-to-knee ratio ({rho} = 0.765, p = 0.0003), hip asymmetry ratio ({rho} = 0.688, p=0.0023), and knee asymmetry ratio ({rho} = 0.679, p = 0.0028). In contrast, EMG RMS amplitude did not correlate across tasks ({rho} = -0.044, p = 0.873), suggesting task-specific gain of activation magnitude. Stabilometer and tilt board tasks shared a similar coordination structure and showed a high correlation in balance performance and neuromuscular strategy, supporting the tilt board as an internally valid transfer task for stabilometer-based dynamic balance paradigms. Similarity of tasks appears strongest at the level of modular control and strategy organization, with device-specific gain scaling of activation amplitude.

neuroscience↗

bioRxiv2025

Determining perception thresholds of young adults to small continuous moving platform perturbations

Detecting external disturbances is vital for maintaining balance, as corrective actions are initiated to prevent falls. Quantifying peoples ability to perceive such disturbances improves our understanding of how balance is maintained. This study aims to: 1) quantify healthy young adults ability to perceive external perturbations while balancing on a stabilometer, and 2) understand the relationship between balance performance and perturbation magnitude relative to participants perception threshold. Participants (n=22; 20-35 years) completed a multiple staircase protocol. While standing on a stabilometer mounted on a moving platform, they attempted to keep it horizontal during 10-second trials with small continuous perturbations. After each trial, participants were asked whether they perceived the platform movement. Perturbation magnitudes were adjusted for the next trial based on their response. This process continued for each staircase until the termination criteria were met, at which point participants individual perception threshold was determined. Participants then performed ten 40-second trials on the stabilometer, two trials in each condition: without perturbation, perturbation at the 100%, 80%, and 50% of the individuals perception threshold, and the pilot studys minimum threshold. Balance performance was defined as time-in-balance ratio and RMS deviation angle from horizontal. Perception thresholds varied significantly between participants individuals, with an RMS acceleration ranging from 2.67 and 12.80 cm/s2. The results showed that perturbation magnitude has a significant correlation with variability in deviation angle (R=0.24, p=0.0038). The results suggest that some participants can perceive very small perturbations during a challenging balance task. Subthreshold perturbations, although very small, can influence balance performance. NEW & NOTEWORTHYTo our knowledge, this is the first study to quantitatively measure the conscious perception threshold of platform perturbations while doing a balancing task. We found that young healthy adults with little similar prior experience in tasks close to stabilameter balancing task can detect small platform perturbations while doing such challenging task. The results also showed that platform perturbations below conscious threshold can influence the balance performance on the stabilometer.

neuroscience↗

bioRxiv2024

Plasma exosomes from individuals with type 2 diabetes drive breast cancer aggression in patient-derived organoids

Women with obesity-driven diabetes (T2D) are predisposed to more aggressive breast cancers, yet patient metabolic status does not fully inform current standards of care. We previously identified plasma exosomes as key mediators of intercellular communication and drivers of tumor progression; however, their effect on immune cells within the tumor microenvironment (TME) remains unclear. To model this exosomal signaling, we developed a novel method to generate patient-derived organoids (PDOs) from breast tumor resections, uniquely preserving native tumor-infiltrating lymphocytes (TILs) for the first time. This modifiable and reproducible system provides a robust platform for studying human tumor-immune interactions within the TME in vitro. After 3-day exosome treatment, we assessed the impact of T2D-derived exosomes on PDOs via single-cell RNA sequencing. Exosomes from T2D patient plasma triggered a 13.6-fold expansion of immunosuppressive TILs compared to non-diabetic exosome controls. This immune dysfunction may permit the survival of micrometastases and undermine immune checkpoint therapies, a known challenge for cancer patients with comorbid T2D. Tumor-intrinsic analysis revealed a 1.5-fold increase in intratumoral heterogeneity and approximately 2.3-fold upregulation of epithelial-to-mesenchymal transition, invasiveness, and cancer stemness, consistent with enhanced tumor aggressiveness and metastatic potential of these PDOs. These findings demonstrate how metabolic dysregulation in T2D disrupts tumor-immune crosstalk, profoundly impairing anti-tumor immunity and driving cancer progression through a previously underappreciated exosomal signaling pathway. These insights into the TME could inform personalized treatments for patients with this comorbidity.

cancer biology↗

bioRxiv2022

Novel plasma exosome biomarkers for prostate cancer progression in co-morbid metabolic disease

Comorbid Type 2 diabetes (T2D), a metabolic complication of obesity, associates with worse cancer outcomes for prostate, breast, head and neck, colorectal and several other solid tumors. However, the molecular mechanisms remain poorly understood. Emerging evidence shows that exosomes carry miRNAs in blood that encode the metabolic status of originating tissues and deliver their cargo to target tissues to modulate expression of critical genes. Exosomal communication potentially connects abnormal metabolism to cancer progression. Here, we hypothesized that T2D plasma exosomes induce epithelial-mesenchymal transition (EMT) and immune checkpoints in prostate cancer cells. We demonstrate that plasma exosomes from subjects with T2D induce EMT features in prostate cancer cells and upregulate the checkpoint genes CD274 and CD155. We demonstrate that specific exosomal miRNAs that are differentially abundant in plasma of T2D adults compared to nondiabetic controls (miR374a-5p, miR-93-5p and let-7b-3p) are delivered to cancer cells, thereby regulating critical target genes. We build on our previous reports showing BRD4 controls migration and dissemination of castration-resistant prostate cancer, and transcription of key EMT genes, to show that T2D exosomes require BRD4 to drive EMT and immune ligand expression. We validate our findings with gene set enrichment analysis of human prostate tumor tissue in TGCA genomic data. These results suggest novel, non-invasive approaches to evaluate and potentially block progression of prostate and other cancers in patients with comorbid T2D.

cancer biology↗

bioRxiv2020

High-Throughput Image Analysis of Lipid-Droplet-Bound Mitochondria

Changes to mitochondrial architecture are associated with various adaptive and pathogenic processes. However, quantification of changes to mitochondrial structures are limited by the yet unmet challenge of defining the borders of each individual mitochondrion within an image.. Here, we describe a novel method for segmenting Brown Adipose Tissue (BAT) images. We describe a granular approach to quantifying subcellular structures, particularly mitochondria in close proximity to lipid droplets, peri-droplet mitochondria. In addition, we lay out a novel machine-learning-based mitochondrial segmentation method that eliminates the bias of manual mitochondrial segmentation and improves object recognition compared to conventional thresholding analyses. By applying these methods, we discovered a significant difference between cytosolic and peridroplet BAT mitochondrial H2O2 production, and validated the machine learning algorithm in BAT via norepinephrine-induced mitochondrial fragmentation and comparing manual analyses to the automated analysis. This approach provides a higher-throughput analysis protocol to quantify ratiometric probes in subpopulations of mitochondria in adipocytes.

cell biology↗

bioRxiv2019

Blocking mitochondrial pyruvate import causes energy wasting via futile lipid cycling in brown fat

Futile lipid cycling is an ATP-wasting process proposed to participate in energy expenditure of mature fat-storing white adipocytes, given their inability to oxidize fat. The hallmark of activated brown adipocytes is to increase fat oxidation by uncoupling respiration from ATP synthesis. Whether ATP-consuming lipid cycling can contribute to BAT energy expenditure has been largely unexplored. Here we find that pharmacological inhibition of the mitochondrial pyruvate carrier (MPC) in brown adipocytes is sufficient to increase ATP-synthesis fueled by fatty acid oxidation, even in the absence of adrenergic stimulation. We find that elevated ATP-demand induced by MPC inhibition results from activation of futile lipid cycling. Furthermore, we identify that glutamine consumption and the Malate-Aspartate Shuttle are required for the increase in Energy Expenditure induced by MPC inhibition in Brown Adipocytes (MAShEEBA). These data demonstrate that futile energy expenditure through lipid cycling can be activated in BAT by altering fuel availability to mitochondria. Therefore, we identify a new mechanism to increase fat oxidation and energy expenditure in BAT that bypasses the need for adrenergic stimulation of mitochondrial uncoupling.

biochemistry↗

bioRxiv2017

GPS2 regulates mitochondria biogenesis via mitochondrial retrograde signaling and chromatin remodeling of nuclear-encoded mitochondrial genes

As most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-to-nucleus communication pathways are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a key transcriptional activator of nuclear-encoded mitochondrial genes in mammals. GPS2 regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of the nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and in brown adipose tissue from mice. In the nucleus, GPS2 recruitment to target gene promoters regulates histone H3K9 demethylation and RNA Polymerase II (POL2) activation through inhibition of Ubc13-mediated ubiquitination. Together, these findings reveal an unexpected layer of regulation of mitochondrial gene transcription as they uncover a novel mitochondria-nuclear communication pathway.

molecular biology↗