Biology subjects

Chou, C.-C.

Publications and source records attributed to Chou, C.-C..

10 recordsLinked to original sources

bioRxiv2026

Nuclear LC3 Interactome Profiling Identifies Clathrin Heavy Chain as a Mediator of Nuclear LC3 Translocation in Trabecular Meshwork Cells

Although MAP1LC3B/LC3B (LC3) is best known as a cytoplasmic marker of autophagosome biogenesis, a substantial pool of LC3 resides in the nucleus and shuttles dynamically between nuclear and cytoplasmic compartments, yet the composition and regulation of this nuclear interactome remain poorly defined. Using mass spectrometry-based proteomic profiling of nuclear GFP-LC3 immunoprecipitates from primary human trabecular meshwork (TM) cells, a mechanosensitive ocular cell type, we identified a reproducible nuclear LC3 interactome enriched for proteins containing LC3-interacting region (LIR) and expanded LIR (xLIR) motifs and reported nuclear localization. Among these, clathrin heavy chain (CLTC) emerged as a previously unrecognized nuclear LC3 partner that localizes to the nucleus and colocalizes with nuclear LC3 puncta. CLTC depletion reduced basal LC3-II levels, consistent with a role in autophagosome biogenesis, and markedly impaired nuclear LC3 accumulation induced by both nuclear export blockade with leptomycin B and cyclic mechanical stretch, without altering total CLTC abundance, indicating that CLTC actively promotes LC3 nuclear translocation rather than serving as a passive scaffold. Strikingly, mechanical stress-induced nuclear LC3 trafficking, but not its basal component, was selectively impaired in TM cells derived from glaucoma patients, despite comparable CLTC levels, pointing to a defect in coupling this trafficking pathway to mechanotransduction rather than in the core transport machinery itself. Together, these findings establish nuclear LC3 trafficking as an actively regulated, CLTC-dependent process linked to cytoskeletal and vesicular machinery, and implicate its dysregulation in mechanically stressed glaucomatous cells, providing a framework for understanding how autophagy intersects with nuclear homeostasis, mechanotransduction, and glaucoma pathogenesis.

cell biology↗

bioRxiv2026

Relating layer fMRI signals to acoustics and intracranial neuronal activity in the human auditory cortex in a naturalistic design

Naturalistic auditory perception engages feedforward and feedback dynamics across cortical depths, yet how these are organized in the human auditory cortex has been difficult to verify noninvasively. Here, we examine depth-dependent coupling between neuronal activity and fMRI during passive music listening. Depth-specific fMRI responses were modeled using neuronal oscillation envelopes elicited by the same naturalistic stimuli from a separate group of patients under intracranial EEG monitoring. From deep toward superficial depths, the relationship between oscillatory power and fMRI responses systematically changed: alpha/beta activity (8-30 Hz) was increasingly associated with negative fMRI responses, mapping top-down feedback, while gamma band (>30 Hz) oscillations showed increasingly positive associations. Relative to a purely acoustical fMRI baseline, broadband high-frequency activity (>70 Hz), a proxy for neuronal firing, showed the strongest coupling to BOLD signals at intermediate cortical depths receiving feedforward inputs from earlier auditory pathways. Our findings reveal a spectrolaminar organization of neurovascular coupling in the human auditory cortex.

neuroscience↗

bioRxiv2023

Proteostasis and lysosomal quality control deficits in Alzheimer's disease neurons

Aging is the most prominent risk factor for Alzheimers disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in AD brains remain elusive. Here, we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains aging hallmarks and exhibits AD-linked vulnerabilities. Remarkably, AD tNeurons accumulate proteotoxic deposits, including phospho-Tau and A{beta}, resembling those in AD patient and APP mouse brains. Quantitative tNeuron proteomics identify aging and AD-linked deficits in proteostasis and organelle homeostasis, most notably in endosome-lysosomal components. Lysosomal deficits in aged tNeurons, including constitutive lysosomal damage and ESCRT-mediated lysosomal repair defects, are exacerbated in AD tNeurons and linked to inflammatory cytokine secretion and cell death. Supporting lysosomal deficits centrality in AD, compounds ameliorating lysosomal function reduce A{beta} deposits and cytokine secretion. Thus, the tNeuron model system reveals impaired lysosomal homeostasis as an early event of aging and AD.

cell biology↗

bioRxiv2023

A Comprehensive Enumeration of the Human Proteostasis Network. 2. Components of the Autophagy-Lysosome Pathway

The condition of having a healthy, functional proteome is known as protein homeostasis, or proteostasis. Establishing and maintaining proteostasis is the province of the proteostasis network, approximately 2,700 components that regulate protein synthesis, folding, localization, and degradation. The proteostasis network is a fundamental entity in biology that is essential for cellular health and has direct relevance to many diseases of protein conformation. However, it is not well defined or annotated, which hinders its functional characterization in health and disease. In this series of manuscripts, we aim to operationally define the human proteostasis network by providing a comprehensive, annotated list of its components. We provided in a previous manuscript a list of chaperones and folding enzymes as well as the components that make up the machineries for protein synthesis, protein trafficking into and out of organelles, and organelle-specific degradation pathways. Here, we provide a curated list of 838 unique high-confidence components of the autophagy-lysosome pathway, one of the two major protein degradation systems in human cells.

bioinformatics↗

bioRxiv2022

Electrophysiological population dynamics reveal context dependencies during decision making in human frontal cortex

During economic choice, evidence from monkeys and humans suggest that activity in the orbitofrontal cortex (OFC) encodes the subjective values of options under consideration. Monkey data further suggests that value representations in the OFC are context dependent, representing subjective value in a way influenced by the decision makers recent experience. Using stereo electroencephalography (sEEG) in human subjects, we investigated the neural representations of both past and present subjective values in the OFC, insula, cingulate and parietal cortices, amygdala, hippocampus and striatum. Patients with epilepsy (n=20) reported their willingness to pay--a measure of subjective value--for snack food items in a Becker-DeGroot-Marschack (BDM) auction task. We found that the high frequency power (gamma and high-gamma bands) in the OFC positively correlated with the current subjective value but negatively correlated with the subjective value of the good offered on the last trial - a kind of temporal context dependency not yet observed in humans. These representations were observed at both the group level (across electrode contacts and subjects) and at the level of individual contacts. Noticeably, the majority of significant contacts represented either the present or past subjective value, but not both. A dynamic dimensionality-reduction analysis of OFC population trajectories suggested that the past trial begin to influence activity early in the current trial after the current offer was revealed, and that these two properties--current and past subjective values--dominate the electrophysiological signals. Together, these findings indicate that information about the value of the past and present rewards are simultaneously represented in the human OFC, and offer insights into the algorithmic structure of context-dependent computation during human economic choice.

neuroscience↗

bioRxiv2022

A Comprehensive Enumeration of the Human Proteostasis Network. 1. Components of Translation, Protein Folding, and Organelle-Specific Systems

The condition of having a healthy, functional proteome is known as protein homeostasis, or proteostasis. Establishing and maintaining proteostasis is the province of the proteostasis network, approximately 2,500 genes that regulate protein synthesis, folding, localization, and degradation. The proteostasis network is a fundamental entity in biology with direct relevance to many diseases of protein conformation. However, it is not well defined or annotated, which hinders its functional characterization in health and disease. In this series of manuscripts, we aim to operationally define the human proteostasis network by providing a comprehensive, annotated list of its components. Here, we provide a curated list of 959 unique genes that comprise the protein synthesis machinery, chaperones, folding enzymes, systems for trafficking proteins into and out of organelles, and organelle-specific degradation systems. In subsequent manuscripts, we will delineate the human autophagy-lysosome pathway, the ubiquitin-proteasome system, and the proteostasis networks of model organisms.

bioinformatics↗

bioRxiv2022

Visual stimuli modulate local field potentials but drive no high-frequency activity in human auditory cortex

Neuroimaging studies suggest cross-sensory visual influences in human auditory cortices. Whether these influences reflect active visual processing in human auditory cortices (ACs), which drives neuronal firing and concurrent broadband high-frequency activity (BHFA; >70 Hz), or whether they merely modulate sound processing is still debatable. Here, we presented auditory, visual, and audiovisual stimuli to 16 participants (7 women, 9 men) with stereo-EEG depth electrodes implanted near ACs for presurgical monitoring. Anatomically normalized group analyses were facilitated by inverse modeling of intracranial source currents. Analyses of intracranial event-related potentials (iERP) suggested cross-sensory responses to visual stimuli in ACs, which lagged the earliest auditory responses by several tens of milliseconds. Visual stimuli also modulated the phase of intrinsic low-frequency oscillations and triggered 15-30-Hz event-related desynchronization in ACs. However, BHFA, a putative correlate of neuronal firing, was not significantly increased in ACs after visual stimuli, not even when they coincided with auditory stimuli. Intracranial recordings demonstrate cross-sensory modulations, but no indication of active visual processing in human ACs. Significance StatementVisual information has a profound influence on auditory processing, particularly in noisy conditions. These "cross-sensory" influences start already in auditory cortices, the brain area that processes sound signals. It has, however, been unclear whether auditory cortex actively processes visual information or whether visual signals only change the way sounds are processed. We studied this question by neurophysiological recordings from 16 participants with epilepsy who had electrodes implanted in their brains due to medical reasons. Using these intracranial recordings, we show that cross-sensory visual information modulates sound processing but triggers no high-frequency activity -- a correlate of local neuronal firing -- in auditory cortex. This result provides important information on the role of sensory areas in multisensory processing in the human brain.

neuroscience↗

bioRxiv2022

Task-specific neural processes underlying conflict resolution during cognitive control

Cognitive control involves flexibly combining multiple sensory inputs with task-dependent goals during decision making. Several tasks have been proposed to examine cognitive control, including Stroop, Eriksen-Flanker, and the Multi-source interference task. Because these tasks have been studied independently, it remains unclear whether the neural signatures of cognitive control reflect abstract control mechanisms or specific combinations of sensory and behavioral aspects of each task. To address this question, here we recorded invasive neurophysiological signals from 16 subjects and directly compared the three tasks against each other. Neural activity patterns in the theta and high-gamma frequency bands differed between incongruent and congruent conditions, revealing strong modulation by conflicting task demands. These neural signals were specific to each task, generalizing within a task but not across tasks. These results highlight the complex interplay between sensory inputs, motor outputs, and task demands and argue against a universal and abstract representation of conflict.

neuroscience↗

bioRxiv2020

Distributed source modeling of intracranial stereoelectroencephalographic measurements

Intracranial stereoelectroencephalography (sEEG) provides unsurpassed sensitivity and specificity for human neurophysiology. However, sEEG group analyses are complicated because the electrode implantations differ greatly across individuals. Here, using an auditory experiment as the test case, we developed a distributed, anatomically realistic sEEG source-modeling approach for within- and between-subject analyses. In addition to intracranial event-related potentials (iERP), we also estimated the sources of high broadband gamma activity (HBBG), a putative correlate of local neural firing. The source models accounted for a significant portion of the variance of the sEEG measurements in leave-one-out cross-validation. After logarithmic transformations, the sensitivity and signal-to-noise ratio were linearly inversely related to the minimal distance between the brain location and electrode contacts (slope{approx}-3.6). The HGGB source estimates were remarkably consistent with analyses of intracranial-contact data. In conclusion, distributed sEEG source modeling provides a powerful neuroimaging tool, which facilitates anatomically-normalized group analyses of both iERP and HBBG.

neuroscience↗

bioRxiv2019

variant2literature: full text literature search for genetic variants

MotivationWhole genome sequencing (WGS) by next-generation sequencing produces millions of variants for an individual. The retrieval of biomedical literature for such a large number of genetic variants remains challenging, because in many cases the variants are only present in tables as images, or in the supplementary documents of which the file formats are diverse.\n\nResultsThe proposed tool named variant2literature from the TaiGenomics (Toolkits for AI genomics) resolves the problem by incorporating text recognition with image processing. In addition to the adoption of advanced image-based text retrieval, the recall rate of finding the literature containing the variants of interest is further improved by employing the skill of variant normalization. Different variant presentations are transformed into chromosome coordinates (standard VCF format) such that false negatives can be largely avoided. variant2literature is available in two ways. First, a web-based interface is provided to search all the literature in PMC Open Access Subset. Second, the command-line executable can be downloaded such that the users are free to search all the files in a specified directory locally.\n\nAvailabilityhttp://variant2literature.taigenomics.com/\n\nContactchienyuchen@ntu.edu.tw

genetics↗