Biology subjects

Dunham, J.

Publications and source records attributed to Dunham, J..

2 recordsLinked to original sources

bioRxiv2024

Supervised Spike Sorting Feasibility of Noisy Single-Electrode Extracellular Recordings: Systematic Study of Human C-Nociceptors recorded via Microneurography

Sorting spikes from noisy single-channel in-vivo extracellular recordings is challenging, particularly due to the lack of ground truth data. Microneurography, an electrophysiological technique for studying peripheral sensory systems, employs experimental protocols that time-lock a subset of spikes. Stable propagation speed of nerve signals enables reliable sorting of these spikes. Leveraging this property, we established ground truth labels for data collected in two European laboratories and designed a proof-of-concept open-source pipeline to process data across diverse hardware and software systems. Using the labels derived from the time-locked spikes, we employed a supervised approach instead of the unsupervised methods typically used in spike sorting. We evaluated multiple low-dimensional representations of spikes and found that raw signal features outperformed more complex approaches, which are effective in brain recordings. However, the choice of the optimal features remained dataset-specific, influenced by the similarity of average spike shapes and the number of fibers contributing to the signal. Based on our findings, we recommend tailoring lightweight algorithms to individual recordings and assessing the "sortability feasibility" based on achieved accuracy and the research question before proceeding with sorting of non-time-locked spikes in future projects.

neuroscience↗

bioRxiv2024

KF4 anti-CELA1 Antibody and Purified α1-Antitrypsin Have Similar but Not Additive Efficacy in Preventing Emphysema in Murine α1-Antitrypsin Deficiency

Alpha-1 antitrypsin (AAT) deficiency is the most common genetic cause of emphysema. Chymotrypsin-like Elastase 1 (CELA1) is a serine protease neutralized by AAT and is important in emphysema progression. Cela1-deficiency is protective in a murine models of AAT-deficient emphysema. KF4 anti-CELA1 antibody prevented emphysema in PPE and cigarette smoke models in wild type mice. We evaluated potential toxicities of KF4 and its ability to prevent emphysema in AAT deficiency. We found Cela1 protein expression in mouse lung, pancreas, small intestine, and spleen. In toxicity studies, mice treated with KF4 25 mg/kg weekly for four weeks showed an elevation in blood urea nitrogen and slower weight gain compared to lower doses or equivalent dose IgG. In histologic grading of tissue injury of the lung, kidney, liver, and heart, there was some evidence of liver injury with KF4 25 mg/kg, but in all tissues, injury was less than in control mice subjected to cecal ligation and puncture. In efficacy studies, KF4 doses as low as 0.5 mg/kg reduced the lung elastase activity of AAT-/-mice treated with 0.2 units of PPE. In this injury model, AAT-/-mice treated with KF4 1 mg/kg weekly, human purified AAT 60 mg/kg weekly, and combined KF4 and AAT treatment had less emphysema than mice treated with IgG 1 mg/kg weekly. However, the efficacy of KF4, AAT, or KF4 & AAT was similar. While KF4 might be an alternative to AAT replacement, combined KF4 and AAT replacement does not confer additional benefit.

pathology↗