Biology subjects

Doshi, R.

Publications and source records attributed to Doshi, R..

3 recordsLinked to original sources

bioRxiv2026

Engineered 3D hydrogel model reveals divergence of adhesion-migration balance in Glioblastoma under simulated microgravity

Glioblastoma is an aggressive brain cancer whose cells can switch between different modes of invasion in response to their surroundings, making the disease difficult to predict and treat. How physical forces influence this adaptability remains poorly understood. Here, we used simulated microgravity together with engineered hydrogels that independently control adhesion, degradability, and mechanical properties to test how gravity affects glioblastoma invasion. Microgravity strongly reduced invasion and shifted cells from elongated, protrusive behavior to a more cohesive state. Proteomic analysis showed reduced invasive signaling together with increased cell-matrix and cell-cell adhesion, consistent with a redistribution of contractile forces toward the cell edge. Under normal gravity, blocking CD44, integrin {beta}1, or N-cadherin reduced matrix-dependent invasion. In contrast, under microgravity, inhibiting these same adhesion pathways restored invasion, indicating that microgravity traps cells in an overly adhesive, cohesive state that limits movement rather than motility itself. These findings show that gravity is an important regulator of cancer cell plasticity and reveal a mechanically induced vulnerability in glioblastoma invasion. More broadly, combining defined biomaterials with gravitational modulation provides a new way to study how physical forces shape tumor behavior.

cancer biology↗

bioRxiv2025

Corticospinal excitability during timed interception depends on the speed of the moving target

Successfully intercepting a moving object requires precisely timing the optimal moment to act by integrating information about the targets visual motion properties. Neurophysiological evidence indicates that activity in the primary motor cortex (M1) during interception preparation is sensitive to both the targets kinematic features and motor planning. However, how visual motion signals are integrated within M1 to guide interception timing is unclear. In the present study, we applied single-pulse transcranial magnetic stimulation (TMS) over M1 to examine how a targets kinematics influence corticospinal excitability during interception preparation. Participants were instructed to abduct their right index finger to intercept a target moving horizontally at a constant speed toward a fixed interception zone. Target speed (Fast or Slow) and travel distance (Far or Close) were manipulated while controlling motion duration across conditions. Motor-evoked potentials (MEPs) were elicited at five latencies before target arrival at the interception zone. Consistent with previous behavioral findings, movement initiation occurred earlier for faster targets and was delayed when TMS was applied closer to the targets arrival. Though MEPs were generally suppressed relative to baseline at earlier timepoints and facilitated closer to movement initiation, we observed that target speed--but not distance--influenced the time course of MEP modulation. When adjusting for movement initiation times, there was an overall reduced suppression and increased facilitation for faster-moving targets, possibly reflecting a heightened urgency to move. These results suggest M1 activity during interception preparation integrates internal estimates of target motion, which may serve to optimize interception timing and performance. New & NoteworthyWhen intercepting a moving object, like catching a ball, we need to continuously combine visual motion signals to predict the objects future location and enable accurate movement. Here, we show that preparatory suppression and facilitation of corticospinal excitability depends on the speed, but not the distance, of the moving target. These findings reveal that differences in interception timing are closely linked to changes in motor system excitability.

neuroscience↗

bioRxiv2017

Functional characterization and discovery of modulators of SbMATE, the agronomically important aluminium tolerance transporter from Sorghum bicolor

About 50% of the worlds arable land is strongly acidic (soil pH < 5). The low pH of these soils solubilizes root-toxic ionic aluminium (Al3+) species from clay minerals, driving the evolution of various counteractive adaptations in cultivated crops. The food crop Sorghum bicolor, for example, upregulates the membrane-embedded transporter protein SbMATE in its roots. SbMATE mediates efflux of the anionic form of the organic acid, citrate, into the soil rhizosphere, chelating Al3+ ions and thereby imparting Al-resistance based on excluding Al+3 from the growing root tip. Here, we use electrophysiological, radiolabeled, and fluorescence-based transport assays in two heterologous expression systems to establish a broad substrate recognition profile of SbMATE, showing the transport of 14C- citrate anion, as well as the organic monovalent cation, ethidium, but not the divalent ethidium-derivative, propidium. The transport cycle is proton and/or sodium-driven, and shares certain molecular mechanisms with bacterial MATE-family transporters. We further complement our transport assays by directly measuring substrate binding to detergent-purified SbMATE protein. Finally, we use the functionally-folded, purified membrane protein as an antigen to discover high-affinity, native conformation-binding and transport function-altering nanobodies using an animal-free, mRNA/cDNA display technology. Our results demonstrate the utility of using Pichia pastoris as an efficient eukaryotic host to express large quantities of functional plant transporter proteins for in vitro characterization. The nanobody discovery approach is applicable to other low immunogenic plant proteins.

plant biology↗