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Karmacharya, S.

Publications and source records attributed to Karmacharya, S..

2 recordsLinked to original sources

Functional organizational principle evaluated by microstimulation in the cortical facial motor areas

Facial gestures are crucial for social interactions among all primates. Since these actions are performed in the absence of direct visual feedback, their effectiveness relies on their stereotypical, almost reflexive patterns. One efficient mechanism for controlling ethological actions could involve motor cortical action maps (Graziano et al., 2002; 2016). Here, we studied whether stereotypical socio-communicative facial expressions are organized into discrete cortical zones by applying long-duration, supra-threshold microstimulation to fMRI-identified cortical areas of the facial motor system. Our findings revealed that these stimulation parameters produced complex facial responses by engaging multiple facial regions but did not elicit social-communicative facial behavior. The effects of long-duration stimulation appeared to be an amplified (both spatially and temporally) version of the responses seen with short-duration stimulation. The stimulation-evoked neural activity extended across the facial motor system, suggesting that these cortical regions function as part of a large-scale network designed to generate coherent, context-specific, and socially relevant motor outputs.

neuroscience↗

Amino Acid and Glucose Fermentation Maintain ATP Content in Mouse and Human Malignant Glioma Cells

Energy is necessary for tumor cell viability and growth. Aerobic glucose-driven lactic acid fermentation is a common metabolic phenotype seen in most cancers including malignant gliomas. This metabolic phenotype is linked to abnormalities in mitochondrial structure and function. A luciferin-luciferase bioluminescence ATP assay was used to measure the influence of amino acids, glucose, and oxygen on ATP content and viability in mouse (VM-M3 and CT-2A) and human (U-87MG) glioma cells that differed in cell biology, genetic background, and species origin. Oxygen consumption was measured using the Resipher system. Extracellular lactate and succinate were measured as end products of the glycolysis and glutaminolysis pathways, respectively. The results showed that: 1) glutamine was a source of ATP content irrespective of oxygen. No other amino acid could replace glutamine in sustaining ATP content and viability; 2) ATP content persisted in the absence of glucose and under hypoxia, ruling out substantial contribution through either glycolysis or oxidative phosphorylation (OxPhos) under these conditions; 3) Mitochondrial complex IV inhibition showed that oxygen consumption was not an accurate measure for ATP production through OxPhos. The glutaminase inhibitor, 6-diazo-5-oxo-L-norleucine (DON), reduced ATP content and succinate export in cells grown in glutamine. The data suggests that mitochondrial substrate level phosphorylation in the glutamine-driven glutaminolysis pathway contributes to ATP content in these glioma cells. A new model is presented highlighting the synergistic interaction between the high-throughput glycolysis and glutaminolysis pathways that drive malignant glioma growth and maintain ATP content through the aerobic fermentation of both glucose and glutamine. Summary statementMalignant gliomas, regardless of cell of origin or species, rely on fermentation mechanisms for ATP production due to OxPhos insufficiency. Glucose and glutamine together are necessary and sufficient for dysregulated tumor cell growth, whereas OxPhos is neither necessary nor sufficient.

cancer biology↗