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Ravikumar, P.

Publications and source records attributed to Ravikumar, P..

4 recordsLinked to original sources

Electrokinetic active grooves for liposome capture, confinement, trajectory analysis and controlled release

Extracellular vesicles (EVs) are attractive candidates for minimally invasive disease monitoring. EV diagnostic signals often reside in low-abundant subpopulations, motivating single-vesicle measurements that can report distributions rather than ensemble averages. In practice, such assays rely on transient migration of a mobile vesicle through a detection region or performing cycled processing/measurement steps on vesicles permanently immobilized on surfaces via affinity-based capture. Single vesicle analysis would benefit from technologies that can combine characteristics of transient detection and surface immobilization to enable controlled capture, fixed time analysis and release of vesicles in a marker-neutral way. Here, we present electrokinetically active (RECON) grooves that provides low-voltage, programmable capture, timed retention, and release of nanoscale vesicles within microscopic grooves under continuous optical access. The platform uses a titanium embedded electrode with thin TiO2 passivation, enabling stable actuation over multi-hour experiments. Using fluorescent, size-defined liposomes as standards, we demonstrate (1) reversible, minute-long confinement at <5 V, (2) size-dependent confinement times, and (3) optical quantification of groove-guided drift velocities. Together, these results establish RECON grooves as a reusable, electrically programmable platform for controlled capture, timed retention, and release, while providing quantitative, trajectory-derived measures of confinement and transport.

biophysics↗

Flexible, task-dependent bimanual coordination along movement direction and extent

Recent work suggests that coordination of bilateral arm movements is mediated through flexible, task-dependent control policies rather than coupled motor commands that activate homologous muscle groups in the two arms. Here we examined whether such flexibility in bimanual control extends independently across movement direction and extent. We employed a bimanual reach task in which we altered the contribution of each arm to the perpendicular (direction axis) and/or parallel (extent axis) position of a single feedback cursor controlled by both arms together. We first replicated findings of Kitchen et al. (2023) showing that when one arm contributed more to perpendicular cursor motion, its lateral variability was reduced, while variability of the other arm increased. We then extended this result to perturbations affecting movement extent, observing similar asymmetric adjustments in variability in the parallel direction. Subsequent manipulations where contributions along both axes were manipulated simultaneously, revealed that irrespective of the gain combinations, the arm with the higher perpendicular contribution showed reduced lateral variability and the arm with the higher parallel contribution demonstrated restricted parallel variability, while allowing the corresponding lower contribution arms to compensate for perturbation-induced errors. These results suggest that: 1) the sensorimotor system always prioritizes corrections for deviations directly impacting task goals while tolerating higher variability in less relevant dimensions, and 2) that it is capable of adjusting coordination along movement direction and extent largely independently based on peripheral task demands. These findings add to the growing body of evidence supporting task-dependent modulation of bimanual motor coordination. SIGNIFICANCE STATEMENTBimanual actions in humans are thought to be controlled via a control policy that can be flexibly tuned to task demands. This work aimed to demonstrate that such flexibility in control extends independently to movement direction and extent. We used a shared-cursor bimanual reaching task to selectively manipulate the contribution of each arm to cursor motion along the direction and extent axes first in isolation, then simultaneously. Our results show that the sensorimotor system restricts variability in the more task-relevant arm along each axis, enabling axis-specific coordination. These findings thus provide evidence that bimanual coordination along movement direction and extent can be governed flexibly and largely independently in response to changing task demands.

neuroscience↗

Deciphering Global Patterns of Marine Microbial Community Assembly and Network Stability

Microbial community assembly processes can help us understand ecology, evolution, and climatic influences on community composition while presenting opportunities for biotechnological applications and improved marine conservation. In this study, we have investigated species richness patterns, community assembly mechanisms, and interaction patterns of marine microbial communities by analysing 16S rRNA amplicon sequencing data from 4,611 samples collected from major ocean microbiome projects. Using neutral community models, the iCAMP framework, and co-occurrence network analyses, we showed that stochastic processes drive microbial community assembly across all latitude zones. Drift was the primary driver of community assembly in polar communities. The polar microbial communities exhibited the highest modularity and network robustness, but were more vulnerable to hub removal. While previous studies have attributed higher stability of the polar communities to environmental filtering, our analyses reveal that the resilience of the community is dependent on a few central taxa. By classifying the genera as generalists and specialists, we further highlight the role played by the specialist taxa in maintaining the stability of the marine microbial community, especially under the pressures of climate change and global warming. Overall, our findings offer a latitudinal perspective on ocean microbial community stability and the effect of anthropogenic disturbances on these communities.

systems biology↗

Impaired tumor death receptor signaling drives resistance to CAR T cell therapy

Cellular immunotherapy using T cells engineered to express chimeric antigen receptors targeting CD19 (CART19) leads to long-term remission in patients with B-cell malignancies1-5. Unfortunately, a significant fraction of patients demonstrate primary resistance to CART19 or experience relapse after achieving remission. Beyond loss of target antigen, the molecular pathways governing CART19 failure are unknown. Here we demonstrate that death receptors, cell surface signaling molecules that induce target cell apoptosis, are key mediators of leukemic resistance and CART19 failure. Using a functional CRISPR/Cas9-based genome-wide knockout screen6 in B-cell acute lymphoblastic leukemia (ALL), we identified the death receptor signaling pathway as a central regulator of sensitivity to CART19-induced cell death. In the absence of the pro-apoptotic death receptor signaling molecules BID or FADD, ALL cells were resistant to CART19 cytotoxicity, resulting in rapid disease progression in mice. We found that this initial resistance to cytotoxicity led to persistence of tumor cells, which drove the development of T cell dysfunction that further compromised anti-tumor immunity and permitted tumor outgrowth. We validated these findings using clinical samples collected from patients with ALL treated with CD19-targeted CAR T cells and found that expression of pro-apoptotic death receptor pathway genes in pre-treatment tumor samples correlated with CAR T cell expansion and persistence, as well as patient response and overall survival. Our findings indicate that tumor-intrinsic death receptor signaling directly contributes to CAR T cell failure.

immunology↗