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Wright, C. E.

Publications and source records attributed to Wright, C. E..

2 recordsLinked to original sources

Sensing Local Field Potentials with a Directional and Scalable Depth Array: DISC

A variety of electrophysiology tools are available to the neurosurgeon for diagnosis, functional therapy, and neural prosthetics. However, no tool can currently address these three critical needs: (i) access to all cortical regions in a minimally invasive manner; (ii) recordings with microscale, mesoscale, and macroscale resolutions simultaneously; and (iii) access to spatially distant multiple brain regions that constitute distributed cognitive networks. We present a novel device for recording local field potentials (LFPs) with the form factor of a stereo-electroencephalographic electrode but combined with radially positioned microelectrodes and using the lead body to shield LFP sources, enabling directional sensitivity and scalability, referred to as the DISC array. As predicted by our electro-quasistatic models, DISC demonstrated significantly improved signal-to-noise ratio, directional sensitivity, and decoding accuracy from rat barrel cortex recordings during whisker stimulation. Critically, DISC demonstrated equivalent fidelity to conventional electrodes at the macroscale and uniquely, revealed stereoscopic information about current source density. Directional sensitivity of LFPs may significantly improve brain-computer interfaces and many diagnostic procedures, including epilepsy foci detection and deep brain targeting.

bioengineering

Autocrine Signaling by Receptor Tyrosine Kinases in Urothelial Carcinoma of the Bladder

Comprehensive characterizations of bladder cancer (BCa) have established molecular phenotype classes with distinct alterations and survival trends. Extending these studies within the tyrosine kinase (TK) family to identify disease drivers could improve our use of TK inhibitors to treat specific patient groups or individuals. We examined the expression distribution of TKs as a class (n = 89) in The Cancer Genome Atlas (TCGA) muscle invasive BCa data set (n >400). Patient profiles of potentially oncogenic alterations (overexpression and/or amplification) clustered TKs into 3 groups; alterations of group 1 and 3 TKs were associated with significantly worse patient survival relative to those without alterations. Many TK pathways induce epithelial-to-mesenchymal transition (EMT), which promotes tumor invasiveness and metastasis. Overexpression and/or amplification among 9 EMT transcriptional activators occurred in 43% of TCGA cases. Co-occurring alterations of TKs and EMT transcriptional activators involved most group 1 TKs; 24% of these events were associated with significantly worse patient survival. Co-occurring alterations of receptor TKs and their cognate ligands occurred in 16% of TCGA cases and several BCa-derived cell lines. Suppression of GAS6, MST1 or CSF1, or their respective receptors (AXL, MST1R and CSF1R), in BCa cell lines was associated with decreased receptor activation, cell migration, cell proliferation and anchorage independent cell growth. These studies reveal the patterns and prevalence of potentially oncogenic TK pathway-related alterations in BCa and identify specific alterations associated with reduced BCa patient survival. Detection of these features in BCa patients could better inform TK inhibitor use and improve clinical outcomes.

cancer biology