Biology subjects

McEwan, A.

Publications and source records attributed to McEwan, A..

4 recordsLinked to original sources

bioRxiv2026

Toward Electrical Impedance Tomography of Functional Activity in the Retina

Electrical Impedance Tomography (EIT) is a non-invasive electrical imaging technique that reconstructs spatial variations in tissue conductivity. Traditionally used for thoracic imaging, EIT has recently been extended to neural applications in the brain and peripheral nerves. This study investigates the feasibility of using EIT to image functional neural activity in the retina. We present computational modeling of EIT measurements for image reconstruction of small conductivity perturbations across different layers of the ex-vivo mouse retina with electrodes placed in epiretinal configuration. Experimentally, we describe the design of a multi-electrode array suitable for impedance measurements under these conditions and report preliminary recordings of light-evoked impedance changes in response to wide-field optical retinal stimulation. Our computational results suggest that small conductivity perturbations of 200{micro}m diameter and 5% conductivity variation are experimentally detectable by high-end biopotential recording equipment and could be localized by EIT imaging within {approx}13% of inter-electrode distance and {approx}22% of retinal thickness, respectively. In preliminary recordings, we observed slow impedance variations of 13.0{+/-}9.3 {micro}V (0.37{+/-}0.44%) in response to retina-wide light pulse trains, when performing impedance measurements with 10 {micro}A applied current at 2-8 kHz. These variations were characterized by a slow time course, distinct from the fast neural EIT signals associated with action potentials, and may reflect extracellular or metabolic processes linked to retinal activation. Our modelling and technical results support the feasibility of retinal EIT, while the experimental observations are preliminary and motivate further controlled studies. Retinal EIT could significantly advance retinal electrophysiology research and prosthetic development.

neuroscience↗

bioRxiv2026

Open-Source, High-Speed and High-Resolution Data Acquisition Platform for Biopotential Recordings and Neural EIT applications

Objective: Biopotential measurement devices, such as EEG, ECG, and EMG recorders, are available in low-cost, open-source implementations with standard specifications. However, high-end systems remain expensive and predominantly proprietary, limiting accessibility and customization by research laboratories. In addition, neurophysiology techniques such as bioimpedance-based Fast Neural Electrical Impedance Tomography (FN-EIT) also rely on these systems for data acquisition. This work aimed to develop an open-source biopotential recording system using off-the-shelf components that achieves performance comparable to high-end devices. Approach: We designed our system to provide simultaneous sampling over 32 channels, 24-bit resolution, 10 kHz bandwidth, 50 kHz sampling rate, and battery-powered operation while reducing cost by two orders of magnitude. System performance was evaluated comparatively against a reference device. Initial validation involved benchtop recordings in saline solution and standard non-invasive biopotential measurements (ECG and EMG). Further in-vivo validation was performed by recording evoked electrophysiological responses and FN-EIT traces from the sciatic nerve of a rat during tibial branch stimulation. Main results: EMG recordings showed comparable RMS peak amplitudes (814{+/-}153 V vs. 897{+/-}113V, p=0.07), while ECG-derived heart rates closely matched between systems (64.8{+/-}4.0 bpm vs. 65.1{+/-}3.1bpm, p=0.54). During in-vivo recordings, compound action potentials exhibited comparable amplitudes and morphology (129{+/-}26 mV vs 128{+/-}25 mV, P=0.15). FN-EIT recordings showed strongly correlated baseline voltages (R>0.93, P=0.11), sub-microvolt noise levels (0.83{+/-}0.36V vs. 0.42{+/-}0.25V, p<0.05), and comparable impedance variations (0.006{+/-}0.002% vs 0.005{+/-}0.003, P>0.05). FN-EIT images of functional activity recorded with the novel device closely matched reference ones, exhibiting a 98.5% overlap in activated area. Significance: The proposed open-source device has the potential to broaden research access to customizable, high-specification data acquisition hardware and facilitate wider adoption of specialized neural recording techniques such as FN-EIT.

neuroscience↗

bioRxiv2019

A genetic map of the response to DNA damage in human cells

The response to DNA damage is critical for cellular homeostasis, tumor suppression, immunity and gametogenesis. In order to provide an unbiased and global view of the DNA damage response in human cells, we undertook 28 CRISPR/Cas9 screens against 25 genotoxic agents in the retinal pigment epithelium-1 (RPE1) cell line. These screens identified 840 genes whose loss causes either sensitivity or resistance to DNA damaging agents. Mining this dataset, we uncovered that ERCC6L2, which is mutated in a bone-marrow failure syndrome, codes for a canonical non-homologous end-joining pathway factor; that the RNA polymerase II component ELOF1 modulates the response to transcription-blocking agents and that the cytotoxicity of the G-quadruplex ligand pyridostatin involves trapping topoisomerase II on DNA. This map of the DNA damage response provides a rich resource to study this fundamental cellular system and has implications for the development and use of genotoxic agents in cancer therapy.

cancer biology↗

bioRxiv2019

A consensus set of genetic vulnerabilities to ATR inhibition

The response to DNA replication stress in eukaryotes is under the control of the ataxia-telangiectasia and Rad3-related (ATR) kinase. ATR responds to single-stranded (ss) DNA to stabilize distressed DNA replication forks, modulate DNA replication firing and prevent cells with damaged DNA or incomplete DNA replication from entering into mitosis. Furthermore, inhibitors of ATR are currently in clinical development either as monotherapies or in combination with agents that perturb DNA replication. To gain a genetic view of the cellular pathways requiring ATR kinase function, we mapped genes whose mutation causes hypersensitivity to ATR inhibitors with genome-scale CRISPR/Cas9 screens. We delineate a consensus set of 117 genes enriched in DNA replication, DNA repair and cell cycle regulators that promote survival when ATR kinase activity is suppressed. We validate 14 genes from this set and report genes not previously described to modulate response to ATR inhibitors. In particular we found that the loss of the POLE3/POLE4 proteins, which are DNA polymerase e accessory subunits, results in marked hypersensitivity to ATR inhibition. We anticipate that this 117-gene set will be useful for the identification of genes involved in the regulation of genome integrity, the characterization of new biological processes involving ATR, and may reveal biomarkers of ATR inhibitor response in the clinic.

molecular biology↗