Biology subjects

Sudhakar, T.

Publications and source records attributed to Sudhakar, T..

3 recordsLinked to original sources

bioRxiv2021

Single Unit Analysis and Wide-Field Imaging Reveal Alterations in Excitatory andInhibitory Neurons in Glioma

Several studies have attributed the development of tumor-associated seizures to an excitatory-inhibitory imbalance, highlighting the importance of resolving the spatiotemporal interplay of different neuronal populations within the peritumoral microenvironment. We combined methods for microelectrode array recordings and single unit analysis during ictal events with wide-field optical mapping of pyramidal neurons in an ex vivo acute slice model of diffusely infiltrating glioma in Thy1-GCaMP6f mice. This approach allowed for characterization of excitatory and inhibitory populations across an extended peritumoral cortical region. As expected, measures of excitability were increased in tumor-bearing slices compared to control. This was accompanied by marked functional alterations in single units classified as fast-spiking interneurons, including reduced firing, altered timing with respect to excitatory firing, and deficits in surround inhibition. Inhibiting mTOR with AZD8055 reversed these glioma-induced changes to excitatory and inhibitory neuronal populations, suggesting a prominent role for functional mechanisms linked to mTOR activation.

cancer biology↗

bioRxiv2020

Variability in the diet diversity of catfish highlighted through DNA barcoding

Identification and quantification of fish diet diversity was the first step in understanding the food web dynamics and ecosystem energetics, where the contribution of DNA barcoding technique has been important. We used DNA barcoding to identify the stomach contents of a euryhaline, benthophagous catfish Ariius maculatus. From 40 catfish stomach items sampled in two different seasons, we barcoded 67 piscine and macro-invertebrates prey items, identified as belonging to 13 species in 4 major phyla (viz., Chordate, Arthropod, Annelida and Mollusca). It is important to note that the mollusc taxa (Meritrix meritrix and Perna viridis) and a species of fish (Stolephorus indicus) could not be found among the gut contents of A. maculatus sampled during the pre- and post-monsoon season, respectively. Among the piscine diets of A. maculatus, Eubleekeria splendens (23.5%) and Stolephorus indicus (23.5%) were the major prey taxa during pre-monsoon season. The hermit crabs forms the major constituents of both pre- and post-monsoon seasons, among invertebrate taxa. Polychaete, Capitella capitata (25.92%) was abundantly consumed invertebrates next to hermit crabs. We noticed that in pre-monsoon A. maculatus was more piscivorous than post-monsoon. As revealed through Kimura-2 parametric pair{-}wise distance analysis, the diet diversity was relatively higher in post-monsoon. The accumulation curve estimated 57 haplotypes within 14 barcoded species (including the host A. maculatus). Majority of haplotypes were found among fishes (47.36%) followed by Arthropods (28.07%), Annelids (14.03%) and Mollusca (10.52%), respectively. This study also highlights that there is a growing concern about A. maculatuss aggressive predation on commercially important stocks of fish and invertebrates. We will continue to expand the coverage of species barcoded in the reference database, which will become more significant as meta- and environmental DNA barcoding techniques become cheaper and prevalent.

zoology↗

bioRxiv2020

Deconvolution of Cell Type-Specific Drug Responses in Human Tumor Tissue with Single-Cell RNA-seq

Precision oncology requires the timely selection of effective drugs for individual patients. An ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity. Here we combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses. We applied this approach to glioblastoma (GBM) and demonstrated that acute slice cultures from individual patients recapitulate the cellular and molecular features of the originating tumor tissue. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients, including unexpected effects on the immune microenvironment. We anticipate that this approach will facilitate rapid, personalized drug screening to identify effective therapies for solid tumors.

cancer biology↗