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Tharayil, J.

Publications and source records attributed to Tharayil, J..

2 recordsLinked to original sources

Spike sorting biases and information loss in a detailed cortical model

Sorting action potentials (spikes) from extracellular recordings of large groups of connected neurons is essential to understanding brain function. Simulations with known spike times have driven significant advances in spike sorting, but present models do not account for neuronal heterogeneity and its effect on sorting accuracy. Here, we used a large-scale detailed cortical microcircuit model to simulate recordings, evaluate modern spike sorters, and link their performance to neuronal heterogeneity. We also exposed the network to various stimuli to investigate how sorting errors affect stimulus discrimination. Spike sorters successfully isolated about 10% of neurons within 50 {micro}m of the electrode shank. This undersampling had no impact on stimulus discrimination ability. However, sorting biases related to firing rate, spike extent, synaptic type, and layer reduced its discrimination ability by nearly half. These findings show realistic models are a complementary method to evaluate and improve spike sorting and, hence, improve our understanding of neural activity.

neuroscience↗

Multi-Niche Human Bone Marrow On-A-Chip for Studying the Interactions of Adoptive CAR-T Cell Therapies with Multiple Myeloma

Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment. Yet, it is unclear which BM niches give rise to MM pathophysiology. Here, we present a 3D microvascularized culture system, which models the endosteal and perivascular bone marrow niches, allowing us to study MM-stroma interactions in the BM niche and model responses to therapeutic CAR-T cells. We demonstrated the prolonged survival of cell line-based and patient-derived multiple myeloma cells within our in vitro system and successfully flowed in donor-matched CAR-T cells. We then measured T cell survival, differentiation, and cytotoxicity against MM cells using a variety of analysis techniques. Our MM-on-a-chip system could elucidate the role of the BM microenvironment in MM survival and therapeutic evasion and inform the rational design of next-generation therapeutics. TEASERA multiple myeloma model can study why the disease is still challenging to treat despite options that work well in other cancers.

cancer biology↗