Biology subjects

Asgari, M.

Publications and source records attributed to Asgari, M..

5 recordsLinked to original sources

bioRxiv2026

Subclonal IDH1/2 Mutations as a Targetable Vulnerability in Vascular Tumors

Despite extensive sequencing, the genetic etiology of sporadic angiosarcoma remains poorly defined (1-3). Maffucci syndrome, characterized by vascular tumors and elevated cancer risk, is driven by mosaic gain-of-function mutations in IDH1/2 (4,5), though these have not been reported in sporadic angiosarcoma. We identify recurrent, low-variant allele frequency hotspot mutations in IDH1/2 in over half of sporadic angiosarcomas. Mutations were validated by Sanger sequencing and immunohistochemistry. Mutant IDH1 endothelial cells promote tumorigenesis through non-cell-autonomous mechanisms, secreting 2-hydroxyglutarate (2-HG) to increase growth factor and endothelial-to-mesenchymal transition gene expression, activate pAkt/pERK signaling, induce DNA methylation changes, and promote anchorage-independent growth, which are reversed by the mutant IDH1 inhibitor ivosidenib. Patients with mosaic IDH1 mutations show reduced serum 2-HG and marked tumor regression following ivosidenib treatment. The clinical efficacy of ivosidenib in vascular tumors with subclonal IDH1 mutations suggests that low VAF IDH1/2 mutations may be a targetable vulnerability in sporadic angiosarcoma. (6,7) Statement of SignificanceWe identify recurrent, low-VAF IDH1/2 mutations in angiosarcoma and provide evidence that these subclonal mutations promote tumorigenesis through non-cell-autonomous mechanisms. Vascular tumors driven by subclonal IDH1 mutations responded dramatically to ivosidenib, thus revealing a novel treatment for a subset of vascular tumors.

cancer biology↗

bioRxiv2025

AFM characterization of early P. aeruginosa aggregates highlights emergent mechanical properties

Pseudomonas aeruginosa (Pa) is a leading cause of chronic lung infections in people with cystic fibrosis (pwCF), where its ability to form resilient, multicellular communities contributes to antibiotic tolerance and long-term persistence. While much of our understanding of Pa biofilms comes from surface-attached models, recent studies have emphasized the clinical relevance of suspended bacterial aggregates - dense, three-dimensional clusters that form early during infection and exhibit key biofilm-like properties. However, the physical characteristics of these aggregates remain poorly defined. Here, we apply atomic force microscopy (AFM) to visualize and quantify the structural and mechanical properties of Pa aggregates formed in synthetic cystic fibrosis sputum medium (SCFM2). Compared to planktonic cultures grown without mucin, aggregates formed in SCFM2 exhibited complex architecture and increased resistance to deformation, as measured by force spectroscopy. These differences emerged despite the absence of mature extracellular matrix components, suggesting that environmental cues and spatial organization alone may be sufficient to enhance aggregate mechanical resilience. Our results demonstrate that AFM provides a powerful, high-resolution approach for studying early-stage bacterial aggregates under physiologically relevant conditions. By resolving structural features and quantifying localized mechanical strength, this method offers new insight into how aggregate architecture contributes to persistence during chronic infection. These findings lay the groundwork for future studies targeting the physical robustness of bacterial communities as an early vulnerability in the pathogenesis of Pa both in CF and in other infection settings.

microbiology↗

bioRxiv2024

Ultrastructural viscoelastic behavior of collagen identified by AFM nano-dynamic mechanical analysis

Soft tissues exhibit predominantly time-dependent mechanical behavior critical for their biological function in organs like the lungs and aorta, as they can deform and stretch at varying rates depending on their function. Collagen type I serves as the primary structural component in these tissues. The viscoelastic characteristics of such tissues, stemming from diverse energy dissipation mechanisms across various length scales, remains poorly characterized at the nanoscale. Prior experimental investigations have predominantly centered on analyzing tissue responses largely attributed to interactions between cells and fibers. Despite many studies on tissue viscoelasticity from scaffolds to single collagen fibrils, the time-dependent mechanics of collagen fibrils at the sub-fibrillar level remain poorly understood. This pioneering study employs atomic force microscopy (AFM) nano-rheometry and indentation testing to examine the viscoelastic characteristics of individual collagen type I fibrils at the ultrastructural level within distinct topographical zones, specifically focusing on gap and overlap regions. Our investigation has unveiled that collagen fibrils display a viscoelastic response that replicates the mechanical behavior of the tissue at the macroscale. Further, our findings suggest a distinct viscoelastic behavior between the gap and overlap regions, likely stemming from variances in molecular organization and cross-linking modalities within these specific sites. The results of our investigation provide unequivocal proof of the temporal dependence of mechanical properties and provides unique data to be compared to atomistic models, laying a foundation for refining the precision of macroscale models that strive to capture tissue viscoelasticity across varying length scales.

biophysics↗

bioRxiv2024

Identifying an optimal anti-gravity assistance level for select functional shoulder movements: A simulation study

The level of assistance torque is one key design parameter for passive shoulder exoskeletons. High assistance levels may perturb arm movements, while low assistance may not provide functional benefits. This study aimed to use computational tools to identify an optimal anti-gravity assistance level for passive shoulder exoskeletons. We used the task space framework to perform biomechanical simulations of arm movements in OpenSim (Stanford, CA, USA). The simulated movements included shoulder elevation and lowering movements in frontal and scapular planes, as well as forward and lateral reaching movements. These movements were simulated across a range of assistance torque levels from 0% (no-assistance) to 100% of the maximum shoulder gravity torque, in increments of 10%. The optimal assistance level was identified based on analysis of hand kinematics, muscular response efficiency, and glenohumeral joint stability. As the assistance level increased from 10% to 40%, the variability of hand movements nearly doubled, and this trend continued for higher assistance levels. The total muscle effort rate was minimized at an assistance level ranging from 20% to 30%. While the stability of the glenohumeral joint was mostly maintained across assistance levels, it decreased slightly at higher assistance levels. The results of this study indicated that, for the simulated movements, an optimal assistance level lies within the range of 20-30% of the maximum gravity torque at the shoulder joint. Assistance levels above 40% could cause undesired effects such as greater variability of end-limb kinematics, reduced muscular efficiency, and compromised glenohumeral joint stability.

bioengineering↗

bioRxiv2020

Design and Performance Evaluation of a Wearable Passive Cable-driven Shoulder Exoskeleton

The mechanical assistance provided by exoskeletons could potentially replace, assist, or rehabilitate upper extremity function in patients with mild to moderate shoulder disability to perform activities of daily living. While many exoskeletons are "active" (e.g. motorized), mechanically passive exoskeletons may be a more practical and affordable solution to meet a growing clinical need for continuous, home-based movement assistance. In the current study, we designed, fabricated, and evaluated the performance of a wearable, passive, cable-driven shoulder exoskeleton (WPCSE) prototype. An innovative feature of the WPCSE is a modular spring-cam-wheel system that can be custom designed to compensate for any proportion of the shoulder elevation moment due to gravity over a large range of shoulder motion. The force produced by the spring-cam-wheel system is transmitted over the superior aspect of the shoulder to an arm cuff through a Bowden cable. The results from mechanical evaluation revealed that the modular spring-cam-wheel system could successfully produce an assistive positive shoulder elevation moment that matched the desired, theoretical moment. However, when measured from the physical WPCSE prototype, the moment was lower (up to 30%) during positive shoulder elevation and higher (up to 120%) during negative shoulder elevation due primarily to friction. Even so, our biomechanical evaluation showed that the WPCSE prototype reduced the root mean square (up to 35%) and peak (up to 33%) muscular activity, as measured by electromyography, of several muscles crossing the shoulder during shoulder elevation and horizontal adduction/abduction movements. These preliminary results suggest that our WPCSE may be suitable for providing movement assistance to people with shoulder disability.

bioengineering↗