Search bioRxiv⌕ Search

Biology subjects

Lopez, K. L.

Publications and source records attributed to Lopez, K. L..

3 recordsLinked to original sources

HAPPILEE: The Harvard Automated Processing Pipeline In Low Electrode Electroencephalography, a standardized software for low density EEG and ERP data

Low-density Electroencephalography (EEG) recordings (e.g. fewer than 32 electrodes) are widely-used in research and clinical practice and enable scalable brain function measurement across a variety of settings and populations. Though a number of automated pipelines have recently been proposed to standardize and optimize EEG preprocessing for high-density systems with state-of-the-art methods, few solutions have emerged that are compatible with low-density systems. However, low-density data often include long recording times and/or large sample sizes that would benefit from similar standardization and automation with contemporary methods. To address this need, we propose the HAPPE In Low Electrode Electroencephalography (HAPPILEE) pipeline as a standardized, automated pipeline optimized for EEG recordings with low density channel layouts of any size. HAPPILEE processes task-free (e.g. resting-state) and task-related EEG, and event-related potential (ERP) data, from raw files through a series of processing steps including filtering, line noise reduction, bad channel detection, artifact rejection from continuous data, segmentation, and bad segment rejection that have all been optimized for low density data. HAPPILEE also includes post-processing reports of data and pipeline quality metrics to facilitate the evaluation and reporting of data quality and processing-related changes to the data in a standardized manner. We describe multiple approaches with both recorded and simulated EEG data to optimize and validate pipeline performance. The HAPPILEE pipeline is freely available as part of HAPPE 2.0 software under the terms of the GNU General Public License at: https://github.com/PINE-Lab/HAPPE.

neuroscience↗

The HAPPE plus Event-Related (HAPPE+ER) Software: A Standardized Processing Pipeline for Event-Related Potential Analyses

Event-Related Potential (ERP) designs are a common method for interrogating neurocognitive function with electroencephalography (EEG). However, the gold standard of preprocessing ERP data is manual-editing - a subjective, time-consuming processes. A number of automated pipelines have recently been created to address the need for standardization, automation, and quantification of EEG data processing; however, few are optimized for ERP analyses (especially in developmental or clinical populations). To fill this need, we propose and validate the HAPPE plus Event-Related (HAPPE+ER) software, a standardized and automated processing pipeline optimized for ERP analyses in EEG data. HAPPE+ER processes event- related potential data from raw files through a series of filtering, line noise reduction, bad channel detection, artifact rejection from continuous data, segmentation, and bad segment rejection methods. HAPPE+ER also includes post-processing reports of both data quality and pipeline quality metrics to facilitate the evaluation and reporting of data processing in a standardized manner. Finally, HAPPE+ER includes a post-processing script to facilitate generating ERP figures and measures for statistical analysis. We describe multiple approaches with both adult and developmental data to optimize and validate pipeline performance. HAPPE+ER software is freely available under the terms of GNU General Public License at https://github.com/PINE-Lab/HAPPE.

neuroscience↗

Galectin-8 senses phagosomal damage and recruits selective autophagy adapter TAX1BP1 to control Mycobacterium tuberculosis infection in macrophages

Mycobacterium tuberculosis (Mtb) infects a quarter of the world and causes the deadliest infectious disease worldwide. Upon infection, Mtb is phagocytosed by macrophages and uses its virulence-associated ESX-1 secretion system to modulate the host cell and establish a replicative niche. We have previously shown the ESX-1 secretion system permeabilizes the Mtb-containing phagosome and that a population (~30%) of intracellular Mtb are recognized within the cytosol, tagged with ubiquitin, and targeted to the selective autophagy pathway. Despite the importance of selective autophagy in controlling infection, the mechanisms through which macrophages sense and respond to damaged Mtb-containing phagosomes remains unclear. Here, we demonstrate that several cytosolic glycan-binding proteins, known as galectins, recognize Mtb-containing phagosomes. We found that galectins-3, -8, and -9 are all recruited to the same Mtb population that colocalizes with selective autophagy markers like ubiquitin, p62, and LC3, which indicates Mtb damages its phagosomal membrane such that cytosolic host sensors can recognize danger signals in the lumen. To determine which galectins are required for controlling Mtb replication in macrophages, we generated CRISPR/Cas9 knockout macrophages lacking individual or multiple galectins and found that galectin-8-/- and galectin-3/8/9-/- knockout macrophages were similarly defective in targeting Mtb to selective autophagy and controlling replication, suggesting galectin-8 plays a privileged role in anti-Mtb autophagy. In investigating this specificity, we identified a novel and specific interaction between galectin-8 and TAX1BP1, one of several autophagy adaptors that bridges cargo and LC3 during the course of autophagosome formation, and this galectin-8/TAX1BP1 interaction was necessary to efficiently target Mtb to selective autophagy. Remarkably, overexpressing individual galectins increased targeting of Mtb to antibacterial autophagy and limited Mtb replication. Taken together, these data imply that galectins recognize damaged Mtb-containing phagosomes, recruit downstream autophagy machinery, and may represent promising targets for host-directed therapeutics to treat Mtb.

microbiology↗