Biology subjects

Cheong, J. H.

Publications and source records attributed to Cheong, J. H..

7 recordsLinked to original sources

bioRxiv2025

Direct Optical Quantification of Chain Collapse, Reduced Dielectric, and Water Release Driving Protein Phase Separation

Biomolecular condensates represent unique microenvironments that organize intracellular biology and promote biochemical reactions. However, the biomolecular interactions driving condensate phase separation are often weak, transient, and heterogeneous. Investigating the structural biology and chemical properties of condensate interiors has therefore proven experimentally challenging, often requiring the use of perturbative probes. To overcome this challenge, we combine label-free optical scattering and vibrational spectroscopy approaches spanning ultraviolet, visible, mid-infrared, and terahertz wavelengths with deep-learning-based ensemble prediction of intrinsically disordered protein conformations. Our experimental and computational results reveal that the intrinsically disordered N-terminal domain of the RNA Deadbox helicase 4 (DDX4) deviates from random coil behavior and undergoes chain collapse that correlates with phase separation, which leads to lower dielectric and reduced water content inside condensates. Our data support a model of DDX4 phase separation whereby chain collapse, reduced dielectric, and water release enhance the strength of multivalent protein-protein interactions within condensates, driving condensate growth and phase separation through positive feedback. Our study addresses the critical driving forces of biomolecular phase separation across a range of length scales, providing quantitative insights into protein-protein/protein-solvent interactions and the chemical properties of condensate interiors.

biophysics↗

bioRxiv2021

Minimal functional alignment of ventromedial prefrontal cortex intracranial EEG signals during naturalistic viewing

The ventromedial prefrontal cortex (vmPFC) has been thought to play an important role in processing endogenous information such as generating subjective affective meaning. Unlike sensory cortex, which processes exogenous information about the external world similarly across individuals, prior work has posited that vmPFC activity may be idiosyncratic to each individual, even when exposed to the same external stimulus. In this study, we recorded local field potentials (LFPs) from intracranial stereotactic electrodes implanted in patients with intractable epilepsy while they watched an emotionally engaging television show episode and evaluated temporal synchronization of these signals across participants in auditory cortex and vmPFC. Overall, we observed markedly lower intersubject synchronization of signals recorded from electrodes implanted in vmPFC compared to auditory cortex. A subset of patients, however, appeared to share similar vmPFC states during the more emotionally salient scenes. This work suggests that the vmPFC is involved in processing affective responses to ongoing experience in a state-like manner, but the specific states and temporal sequences are idiosyncratic to each individual, even when viewing the same television episode.

neuroscience↗

bioRxiv2020

Long-chain polyphosphates impair SARS-CoV-2 infection and replication: a route for therapy in man

Anti-viral activities of long-chain inorganic polyphosphates (PolyPs) against severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection were investigated. In molecular docking analyses, PolyPs interacted with several conserved angiotensin-converting enzyme (ACE)2 and RNA-dependent RNA polymerase (RdRp) amino acids. We thus tested PolyPs for functional interactions in vitro in SARS-CoV-2-infected Vero E6, Caco2 and human primary nasal epithelial cells. Immunofluorescence, qPCR, direct RNA sequencing, FISH and Immunoblotting were used to determine virus loads and transcription levels of genomic(g)RNAs and sub-genomic(sg)RNAs. We show that PolyP120 binds to ACE2 and enhances its proteasomal degradation. PolyP120 shows steric hindrance of the genomic Sars-CoV-2-RNA/RdRP complex, to impair synthesis of positive-sense gRNAs, viral subgenomic transcripts and structural proteins needed for viral replication. Thus, PolyP120 impairs infection and replication of Korean and European (containing non-synonymous variants) SARS-CoV-2 strains. As PolyPs have no toxic activities, we envision their use as a nebulised formula for oropharyngeal delivery to prevent infections of SARS-CoV-2 and during early phases of antiviral therapy.

genetics↗

bioRxiv2019

Predictive factors for the development of peritumoral brain edema after LINAC-based radiation treatment in patients with intracranial meningioma

Background and purposeDisruption of the tumor-brain barrier in meningioma plays a critical role in the development of peritumoral brain edema (PTBE). We hypothesized that osteoporotic conditions may be associated with PTBE occurrence after radiation in patients with intracranial meningioma. MethodsWe measured Hounsfield units (HU) of the frontal skull on simulation brain CT in patients who underwent linear accelerator (LINAC)-based radiation treatment for intracranial meningioma. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off values for several predictive factors. The cumulative hazard for PTBE was estimated and classified according to these factors. Hazard ratios were then estimated to identify independent predictive factors associated with the development of PTBE after radiation in intracranial meningioma patients. ResultsA total of 83 intracranial meningiomas in 76 patients who received LINAC-based radiation treatment in our hospital over an approximate 5-year period were included for the study. We found mean frontal skull HU [≤]630.625 and gross tumor volume >7.194 cc to be independent predictors of PTBE after radiation treatment in patients with meningioma (hazard ratio, 8.38; P=0.021; hazard ratio, 5.78; P=0.034, respectively). In addition, patients who were [≥]65 years showed a marginally significant association with PTBE. ConclusionsOur study suggests that possible osteoporotic conditions, large tumor volume, and older age may be associated with PTBE occurrence after LINAC-based radiation treatment for intracranial meningioma. In the future we anticipate that these findings may enhance the understanding of the underlying mechanisms of PTBE after radiation in meningioma patients.

neuroscience↗

bioRxiv2019

Inter-subject representational similarity analysis reveals individual variations in affective experience when watching erotic movies

We spend much of our life pursuing or avoiding affective experiences. However, surprisingly little is known about how these experiences are represented in the brain and if they are shared across individuals. Here, we explore variations in the construction of an affective experience during a naturalistic viewing paradigm based on subjective preferences in sociosexual desire and self-control using intersubject representational similarity analysis (IS-RSA). We found that when watching erotic movies, intersubject variations in sociosexual desire preferences of 26 heterosexual males were associated with similarly structured fluctuations in the cortico-striatal reward, default mode, and mentalizing networks. In contrast, variations in the self-control preferences were associated with shared dynamics in the fronto-parietal executive control and cingulo-insula salience networks. Importantly, these results were specific to the affective experience, as we did not observe any relationship with variation in preferences when individuals watched neutral movies. Moreover, these results appear to require multivariate representations of preferences as we did not observe any significant results using single summary scores. Our findings demonstrate that multidimensional variations in individual preferences can be used to uncover unique dimensions of an affective experience, and that IS-RSA can provide new insights into the neural processes underlying psychological experiences elicited through naturalistic experimental designs.

neuroscience↗

bioRxiv2018

Endogenous variation in ventromedial prefrontal cortex state dynamics during naturalistic viewing reflects affective experience

How we process ongoing experiences is shaped by our personal history, current needs, and future goals. Consequently, brain regions involved in generating these subjective appraisals, such as the vmPFC, often appear to be heterogeneous across individuals even in response to the same external information. To elucidate the role of the vmPFC in processing our ongoing experiences, we developed a computational framework and analysis pipeline to characterize the spatiotemporal dynamics of individual vmPFC responses as participants viewed a 45-minute television drama. Through a combination of functional magnetic resonance imaging, facial expression tracking, and self-reported emotional experiences across four studies, our data suggest that the vmPFC slowly transitions through a series of discretized states that broadly map onto affective experiences. Although these transitions typically occur at idiosyncratic times across people, participants exhibited a marked increase in state alignment during high affectively valenced events in the show. Our work suggests that the vmPFC ascribes affective meaning to our ongoing experiences.

neuroscience↗

bioRxiv2016

The successor representation in human reinforcement learning

Theories of reward learning in neuroscience have focused on two families of algorithms, thought to capture deliberative vs. habitual choice. \"Model-based\" algorithms compute the value of candidate actions from scratch, whereas \"model-free\" algorithms make choice more efficient but less flexible by storing pre-computed action values. We examine an intermediate algorithmic family, the successor representation (SR), which balances flexibility and efficiency by storing partially computed action values: predictions about future events. These pre-computation strategies differ in how they update their choices following changes in a task. SRs reliance on stored predictions about future states predicts a unique signature of insensitivity to changes in the tasks sequence of events, but flexible adjustment following changes to rewards. We provide evidence for such differential sensitivity in two behavioral studies with humans. These results suggest that the SR is a computational substrate for semi-flexible choice in humans, introducing a subtler, more cognitive notion of habit.

neuroscience↗