Biology subjects

Jeong, B.

Publications and source records attributed to Jeong, B..

17 recordsLinked to original sources

bioRxiv2026

Benzopyrene-induced AHR activation in human ESCs primes premature neurogenesis in brain organoids

Benzo[a]pyrene (BaP), a representative polycyclic aromatic hydrocarbon (PAH), is a widespread environmental toxicant and potent ligand of the aryl hydrocarbon receptor (AHR). Yet, how early developmental exposure to BaP influences human neurodevelopment remains poorly understood. We first examined AHR expression dynamics during human embryonic stem cell (ESC)-derived cerebral organoid development and found that AHR expression was highest at the ESC stage and declined during subsequent differentiation, suggesting a potential window of heightened susceptibility to AHR-mediated environmental perturbations. Based on this observation, ESCs were exposed to BaP (0.1, 1 M) for 7 days prior to organoid generation. BaP exposure did not alter proliferation, cell death, or global transcription of ESCs but increased expression of a subset of AHR target genes. Remarkably, however, organoids derived from BaP-exposed ESCs exhibited profound morphological defects resulting from premature neurogenesis, characterized by disrupted neural rosette organization, reduced EOMES intermediate progenitors, and increased BCL11B neurons. Pharmacological inhibition of AHR with CH-223191 attenuated AHR activation and rescued the progenitor-neuron imbalance. These findings identify AHR signaling as a critical upstream mediator of BaP-induced developmental neurotoxicity and highlight the vulnerability of early pluripotent stages to environmental insults.

neuroscience↗

bioRxiv2026

Comparative Analysis of Relative Ligand Binding Free Energy Simulation Methods: Amber-TI, GROMACS-NETI, OpenMM-FEP, and BLaDE-MSLD

Structure-based drug design has become increasingly important in the pharmaceutical industry for accelerating the discovery of effective drug candidates. In particular, ligand binding free energy serves as a critical metric for predicting drug efficacy during the key stages of hit discovery and lead optimization. Continuous progresses have been made in the prediction of ligand binding free energies, but direct comparisons of different methods using the same force field remain challenging due to their unique implementations into different simulation engines. In this study, we present a direct comparison of four popular methodologies (Amber-TI, GROMACS-NETI, OpenMM-FEP, and BLaDE-MSLD) for calculating relative binding free energies ({Delta}{Delta}Gbind) with the same Amber protein and ligand force fields using MolCube Alchemical Free Energy Simulator (MolCube-AFES), which provides an input generation workflow to support {Delta}{Delta}Gbind calculations of all four methods. We used 80 alchemical transformations (among the JACS benchmark set by Wang et al.) and two additional applications to compare the predicted {Delta}{Delta}Gbind from the four methods against experimental measurements. All four methods reproduced experimentally observed trends with most transformations within {+/-}2 kcal/mol from experiments and show broadly comparable accuracy with no statistically significant performance differences across the benchmark dataset. These results demonstrate that MolCube-AFES enables controlled, cross platform benchmarking and show that all four different alchemical free energy methods deliver statistically equivalent accuracy, with method selection guided by workflow requirements such as throughput, portability, and perturbation network design rather than expected differences in performances.

biophysics↗

bioRxiv2026

Policy precision reveals action-phase impulsivity in women with premenstrual syndrome during risk-taking

The Balloon Analogue Risk Task (BART) is widely used to assess risk-taking and impulsivity, yet existing computational models struggle to unify sequential and prior evaluation strategies or fully capture uncertainty-driven information-seeking behavior. To address this, we introduce a novel computational framework grounded in the Active Inference Framework (AIF), which conceptualizes behavior as the minimization of expected free energy. Model comparisons demonstrate that AIF-based models statistically outperform existing benchmarks. Furthermore, we applied this framework to investigate impulsivity in women with Premenstrual Syndrome (PMS). Our model revealed that the PMS group exhibited significantly higher values in inverse precision of policy ({beta}0) and the phase difference of this parameter was only observed in PMS group. This suggests that high {beta}0 serves as a robust computational marker, reflecting both the trait impulsivity inherent in PMS and its state-like exacerbation across the menstrual cycle. Lastly, our findings indicate that impulsivity in PMS manifests not as a learning deficit, but as heightened sensitivity to trial-by-trial sequential evaluation at the expense of stable, pre-planned prior policies. This framework provides a neurobiologically plausible and mechanistically granular understanding of risk-taking, offering new avenues for computational psychiatry.

neuroscience↗

bioRxiv2025

A single Musashi gene allele is sufficient to maintain mouse photoreceptor cells

In vertebrates, two genes, Musashi1 (Msi1) and Musashi2 (Msi2), encode for highly similar Musashi protein paralogs. The Musashi proteins are known to bind to 3-UTRs and control translation. In photoreceptor cells, the Musashi proteins promote the inclusion of photoreceptor-specific alternative exons by binding to the proximal downstream of their introns. While the Musashi proteins are expressed in various cell types, their role in regulating splicing appears to be confined to photoreceptor cells, where the two proteins have exceptionally high expression levels. To test if the photoreceptor-specific role of MSI1 and MSI2 in splicing is due to their expression levels in photoreceptor cells, we generated combined Msi1 and Msi2 knockouts that progressively reduced the number of Musashi alleles in photoreceptor cells. We analyzed the splicing of photoreceptor-specific exons in the Cc2d2a, Cep290, Prom1, and Ttc8 genes and the function of photoreceptor cells in the knockouts. We found that a single allele from either Msi1 or Msi2 is sufficient to maintain photoreceptor function and support high inclusion levels of the photoreceptor-specific exons.

genetics↗

bioRxiv2025

Site-specific replacement of large-scale DNA fragments in human cells

Despite advances in genome editing1-4, precisely replacing large-scale fragments in human cells remains a significant challenge. Here, we present a site-specific gene replacement tool, named Prime Assembly (PA), which adapts prime editors to produce one or two pairs of 3-flaps on both the genome and donor plasmids. These 3-flaps anneal to each other precisely, similar to "Gibson Assembly" in DNA oligonucleotides5, allowing megabase-scale genomic excision and/or kilobase-scale donor insertion at the gene of interest. The PA system achieves an efficiency of up to 57.8% in replacing endogenous sequences with a 2.9 kbp donor DNA fragment in HEK293T cells, and presents an accuracy of more than 99% for integrated PA fragments. Ultimately, the site-specific replacement of large-scale coding sequences (CDSs) in disease-related genes can restore gene function across numerous patients with different mutations, providing a gene implantation technique for genome editing and a universal therapeutic approach.

molecular biology↗

bioRxiv2025

Engineered ADARs enable single-nucleotide resolution DNA A-to-G editing without bystander effects

The adenine base editor (ABE), which enables A*T-to-G*C base conversion, has emerged as a powerful tool for therapeutic applications. However, conventional ABEs suffer from bystander nucleotide conversions, limiting their utility for precise editing. Here, we present a single-nucleotide resolution ABE (snuABE) created by fusing a nickase Cas9, nCas9(H840A), with the deaminase domain of ADAR, which acts on DNA:RNA hybrids, instead of TadA, which acts on single-stranded DNA in conventional ABEs. snuABE requires a specially designed target-adenine guide RNA (tagRNA) that introduces a mismatch at the target adenine, enabling highly specific A-to-G editing by ADAR. Engineering ADAR from Pediculus humanus using the in silico protein evolution algorithm EvolvePro, along with 3-end protection of the tagRNA, further enhances the editing activity of snuABE in human cells. Moreover, snuABE exhibits significantly reduced DNA off-target activity, highlighting its potential as a safer and more precise base editing technology for therapeutic applications.

bioengineering↗

bioRxiv2025

The role of lipoteichoic acid in Staphylococcus aureus cell wall integrity

In Staphylococcus aureus, lipoteichoic acid (LTA) is crucial for growth, cell division, osmoprotection, and beta-lactam resistance, yet its molecular mechanisms remain unclear. This study reveals that LTA binds to multiple proteins involved in cell wall processes and preserves cell wall integrity by regulating one of the LTA-binding proteins, ScaH. ScaH is a peptidoglycan hydrolase predicted to have N-acetylglucosaminidase and amidase/peptidase activities. LTA inhibits ScaHs enzymatic activities by direct binding and represses scaH transcription by an unknown mechanism. During early growth, LTA is highly expressed and sequesters ScaH at the cell membrane, preventing ScaH activity in the cell wall. However, LTA expression decreases during the late growth phase, leading to ScaH translocation into the cell wall. This reduction in LTA coincides with increased wall teichoic acid (WTA) expression and cleavage of the LTA synthase LtaS. In the LTA-null mutant, ScaH inactivation restored peptidoglycan crosslinking, osmoresistance, and beta-lactam resistance both in vitro and in vivo. These findings suggest that LTA protects the cell wall by suppressing ScaH expression and activity while sequestering it during active growth. Additionally, the reciprocal expression patterns of LTA and WTA indicate an interconnected regulation of teichoic acids in S. aureus, with their roles likely depending on the growth phase. ImportanceStaphylococcus aureus is a significant human pathogen, with LTA playing a crucial role in cell viability, division, and maintaining cell wall integrity. Targeting LTA synthesis holds promise for the development of new therapeutics against S. aureus. Disruption of LTA synthesis leads to phenotypes indicative of compromised cell wall integrity, such as reduced crosslinking, osmosensitivity, and heightened beta-lactam sensitivity, although the precise underlying mechanisms remain unclear. Our research demonstrates that LTA contributes to cell wall integrity by regulating the expression, activity, and translocation of the peptidoglycan hydrolase ScaH. Additionally, LTAs binding to the cell wall synthesis enzymes suggests a role in modulating cell wall integrity through these interactions. These findings significantly advance our understanding of LTAs physiological functions and may serve as a foundation for the development of novel therapeutics targeting S. aureus and other Gram-positive pathogens.

microbiology↗

bioRxiv2024

Attention networks engage the default mode network related to policy precision under uncertainty

Behavioural modelling of decision-making processes has advanced our understanding of impairments associated with various psychiatric conditions. However, as research increasingly prioritises the development of models that best explain observed behaviour, the question of whether these behaviours stem from biologically plausible brain functions has often been overlooked. To address this gap, we developed a probabilistic two-armed bandit task model based on the active inference framework and compared its performance to established reinforcement learning (RL) models. Our model demonstrated superior explanatory power in capturing individual variability in choice behaviour. A key parameter in our model, policy precision--analogous to the temperature parameter in RL models--is also optimised based on previous outcomes. This optimisation accounts for the balance between model-free (MF) and model-based (MB) decision-making strategies. Notably, incorporating the rate of change in policy precision enhanced the models ability to explain brain network dynamics and their inter-subject correlations. Specifically, we observed a positive correlation with default mode network dominance and a negative correlation with dorsal attention and frontoparietal network-dominant states. These opposing network patterns suggest a cooperative relationship, as evidenced by correlations between state transitions and behavioural parameters. This transition may represent a neural mechanism underlying MB-MF arbitration, which appears to be disrupted by prolonged activation of another state characterised by heightened ventral attention network activity and increased inter-network connectivity. Finally, we found that reduced prior policy precision in loss-related context is associated with suicidal ideation in individuals with major depressive disorders. HighlightsO_LIThe AIF model explains pronounced individual behavioural variability. C_LIO_LINeural signals are better explained by changes in policy precision. C_LIO_LIThe anti-correlation can be explained from the perspective of the MB-MF arbitration. C_LIO_LIThe AIF model better explains the HAM-D score. C_LIO_LIThe AIF model can discriminate suicidal ideation in MDD with a loss task. C_LI

neuroscience↗

bioRxiv2023

Emotion Dynamics in Reciprocity: Deciphering the Role of Prosocial Emotions in Social Decision-making

To date, the relevance of prosocial emotions in social decisions based on reciprocity remains poorly understood. Expected and experienced emotions in interoceptive-social dimension, expected offers, and actual acceptance were measured in 476 participants during an ultimatum game consisting of fair, moderate, and unfair offers. We investigated whether participants adjust social decisions according to prediction errors on prosocial emotions and reciprocity. Participants acceptance trajectories were explained by prediction errors in dominance, valence, and reward. Participants were categorized into 4 distinct subgroups based on their patterns of reward expectation, acceptance, and emotional experiences before and after the offer. Furthermore, the relationships between prosocial emotions, social decisions, and reciprocity varied across these subgroups. This studys measurement and analysis of multidimensional trajectories across four affect dimensions reveal that social decisions are influenced by the responders perception of partners reciprocity, as well as by the subsequent prediction error of basic and prosocial emotion.

neuroscience↗

bioRxiv2022

Variability and Impact of Musculoskeletal Modeling Parameters for the Human Elbow

Musculoskeletal modeling has significant potential as a translational and clinical research tool for examining neuromuscular injuries and disorders. However its adoption has been limited due, in part, to the difficulty of measuring the subject-specific physiological measures that define model parameters. These measurements may require substantial time and expensive methods, such as MRI, to determine the parameters of a model and thus ensure its accuracy. We used a Monte Carlo simulation to examine the impact of parameter variability on the ill-defined, inverse approximation of muscle activity. We first amalgamated previously published measurements of the physiological characteristics of the upper/lower arm and the biceps/triceps muscles. We then used the observed distributions of these measurements to set physiologically plausible boundaries on uniform distributions and then generated perturbed parameter sets. We computed the root mean squared error (RMSE) between muscle activity patterns generated by the perturbed model parameters to those generated by the original parameters. Regression models were fit to the RMSE of the approximated muscle activity patterns to determine the sensitivity of the simulation results to variation in each parameter. We found that variation in parameters associated with muscle physiology had the most effect on RMSE, suggesting that these parameters may require subject-specific scaling, whereas parameters associated with skeletal bodies had less effect, and might be safely approximated by their population means.

bioengineering↗

bioRxiv2022

Effects of parental verbal abuse experience on the Glutamate response to swear words in the ventromedial prefrontal cortex: A functional H1-magnetic resonance spectroscopy study

Several lines of evidence indicate verbal abuse (VA) critically impacts the developing brain; however, whether VA results in changes in brain neurochemistry has not been established in humans. Here, we hypothesized that exposure to recurrent parental VA elicits heightened glutamate (Glu) responses during the presentation of swear words, which can be measured with functional magnetic resonance spectroscopy (fMRS). During an emotional Stroop task consisting of blocks of color and swear words, metabolite concentration changes were measured in the ventromedial prefrontal cortex (vmPFC) and the left amygdalohippocampal region (AMHC) of healthy adults (14 F/27 M, 23{+/-}4 years old) using fMRS. The dynamic changes in Glu and their associations with the emotional state of the participants were finally evaluated based on 36 datasets from the vmPFC and 30 from the AMHC. A repeated-measures analysis of covariance revealed a modest effect of parental VA severity on Glu changes in the vmPFC. Furthermore, the total score on the Verbal Abuse Questionnaire by parents (pVAQ) was associated with the Glu response to swear words ({Delta}GluSw e). The interaction term of {Delta}GluSw e and baseline N-acetyl aspartate (NAA) level in the vmPFC could be used to predict state-trait anxiety level and depressive mood. We could not find any significant associations between {Delta}GluSw e in the AMHC and either pVAQ or emotional states. We conclude that parental VA exposure in individuals is associated with a greater Glu response towards VA-related stimuli in the vmPFC and that the accompanying low NAA level may be associated with anxiety level or depressive mood.

neuroscience↗

bioRxiv2022

The Musashi proteins are post-transcriptional activators of protein expression and alternative exon splicing in vertebrate photoreceptors

The Musashi proteins, MSI1 and MSI2, are conserved RNA binding proteins with a role in the maintenance and renewal of stem cells. Contrasting with this role, retina and terminally differentiated photoreceptor cells express high levels of MSI1 and MSI2, indicating that the two proteins have a role unrelated to maintaining undifferentiated cell state. Here we show that the Musashi proteins are essential in mature photoreceptors. Combined knockout of Msi1 and Msi2 lead to loss of the retina response to light and progressive photoreceptor cell death. The two proteins are fully redundant as individual deletion of Msi1 or Msi2 did not produce a phenotype. To define the molecular functions underlying the requirement for Musashi in photoreceptors, we delineated their RNA targets and analyzed the effect of the combined Msi1/Msi2 knockout on transcript levels, pre-mRNA splicing, and protein expressions. We show distinct nuclear and cytoplasmic functions for the Musashi proteins in photoreceptor cells. In the nucleus, Musashi binding to the downstream proximal intron promotes splicing of alternative exons. Surprisingly, four conserved photoreceptor-specific alternative exons in genes critical for vision proved to be dispensable, leaving open questions about the selective pressures that lead to the conservation of these exons and the contribution of alternative splicing to the phenotype of the Musashi knockout. In the photoreceptor cell cytoplasm MSI1 and MSI2 act as activators of protein expression. The combined knockout of Msi1 and Msi2 reduced the levels of multiple proteins including proteins required for vision and photoreceptor survival.

neuroscience↗

bioRxiv2022

Staphylococcus aureus does not synthesize arginine from proline under physiological conditions

The Gram-positive pathogen Staphylococcus aureus is the only bacterium known to synthesize arginine from proline via the arginine-proline interconversion pathway, despite having genes for the well-conserved glutamate pathway. Since the proline-arginine interconversion pathway is repressed by CcpA-mediated carbon catabolite repression (CCR), CCR has been attributed to the arginine auxotrophy of S. aureus. Using ribose as a secondary carbon source, here, we demonstrate that S. aureus arginine auxotrophy is not due to CCR but due to the inadequate concentration of proline degradation product. Proline is degraded by proline dehydrogenase (PutA) into pyrroline-5-carboxylate (P5C). Although the PutA expression was fully induced by ribose, the P5C concentration remained insufficient to support arginine synthesis because P5C was constantly consumed by the P5C reductase ProC. When the P5C concentration was artificially increased by either PutA overexpression or proC-deletion, S. aureus could synthesize arginine from proline regardless of carbon source. In contrast, when the P5C concentration was reduced by overexpression of proC, it inhibited the growth of the ccpA-deletion mutant without arginine. Intriguingly, the ectopic expression of the glutamate pathway enzymes converted S. aureus into arginine prototroph. In an animal experiment, the arginine-proline interconversion pathway was not required for the survival of S. aureus. Based on these results, we concluded that S. aureus does not synthesize arginine from proline under physiological conditions. We also propose that arginine auxotrophy of S. aureus is not due to the CcpA-mediated CCR but due to the inactivity of the conserved glutamate pathway. ImportanceStaphylococcus aureus is a versatile Gram-positive human pathogen infecting various human organs. The bacteriums versatility is partly due to efficient metabolic regulation via the carbon catabolite repression system (CCR). S. aureus is known to interconvert proline and arginine, and CCR represses the synthesis of both amino acids. However, when CCR is released by a non-preferred carbon source, S. aureus can synthesize proline but not arginine. In this study, we show that, in S. aureus, the intracellular concentration of pyrroline-5-carboxylate (P5C), the degradation product of proline and the substrate of proline synthesis, is too low to synthesize arginine from proline. These results call into question the notion that S. aureus synthesizes arginine from proline.

microbiology↗

bioRxiv2020

A critical role for MSI1 and MSI2 in photoreceptor morphogenesis

Musashi family of RNA-binding proteins are known for their role in stem-cell renewal and are negative regulators of cell differentiation. Interestingly, in the retina, Musashi proteins, MSI1 and MSI2 are differentially expressed throughout the cycle of retinal development including robust expression in the adult retinal tissue. To study the role of Musashi proteins in the retina, we generated a pan-retinal and rod photoreceptor neuron specific conditional knockout mouse lacking MSI1 and MSI2. Independent of sex, photoreceptor neurons with simultaneous deletion of Msi1 and Msi2 were unable to respond to light and displayed severely disrupted OS morphology and ciliary defects. The retina lacking Musashi exhibited neuronal degeneration with complete loss of photoreceptors by six months. In concordance with our earlier studies that proposed a role for Musashi in regulating alternative splicing, the loss of Musashi prevented the use of photoreceptor-specific exons in transcripts critical for OS morphogenesis, ciliogenesis and synaptic transmission. Overall, we demonstrate a critical role for Musashi in the morphogenesis of terminally differentiated photoreceptor neurons. This role is in stark contrast with the canonical function of these two proteins in maintenance and renewal of stem cells.

developmental biology↗

bioRxiv2019

Expecting social punishment facilitates control over a decision under uncertainty by recruiting medial prefrontal cortex

In many decision-making situations, uncertainty facilitates suboptimal choices. However, when individuals are in a socially dangerous situation such that wrong choice would lead to a social punishment such as blame of the supervisor, they might try to minimize suboptimal choices to avoid it. In this functional MRI study, 46 participants performed a choice task in which the probability of a correct choice with a given cue and the conditional probability of blame feedback (by making an incorrect choice) changed continuously. Using computational models of behavior, we found that participants optimized their decision by suppressing the decision noise induced by uncertainty. Simultaneously, expecting blame significantly deteriorated participants mood. Model-based fMRI analyses and dynamic causal modeling revealed that the optimization mechanism based on the expectation of being blamed was controlled by a neural circuit centered on right medial prefrontal cortex. These results show novel behavioral and neural mechanisms regarding how humans optimize uncertain decisions under the expectation of being blamed that negatively influences mood.\n\nSignificance StatementPeople occasionally encounter a situation that forces us to make an optimal decision under uncertainty, which is difficult, and a failure to make a good choice might be blamed by their supervisor. Although it might be hard to make right decision, they make more effort to make a good decision, which might help them to escape from the aversive outcome. However, such kind of stressful situation influences our mood to be negative. Using the computational modelling, we showed that participants computed how it is likely to be blamed and this computation motivated people to control uncertainty-induced decision noise by recruiting a neural circuit centered on the medial prefrontal cortex. However, an expectation of being blamed significantly deteriorated participants mood.

neuroscience↗

bioRxiv2019

Heartbeat evokes a dynamically changing cortical theta-synchronized network in the resting state

In the resting state, heartbeats evoke cortical responses called heartbeat-evoked responses (HERs). While previous studies reported regional level HERs, researchers have not determined how heartbeat is processed at the cortical network level. Using resting-state magnetoencephalography data from 87 human subjects of both genders provided by the Human Connectome Project, we first showed that heartbeat increases the phase synchronization between cortical regions in the theta frequency, which forms a network structure, and we called this network a heartbeat-evoked network (HEN). The HEN was not an artefactual increase in phase synchronization. The HEN was partitioned into three modules with connector hubs in each module. The first module contained major interoception-related regions and thus was called a visceromotor-interoceptive network (VIN) displaying the strongest synchronization among modules, suggesting a major role for the VIN in processing heartbeat information. Two modules contained regions involved in the default mode network (DMN). The HEN structure was not fixed, but dynamically changed. The most prominent change was observed at approximately 200 ms after R-peak of the electrocardiogram, which was quantified based on the flexibility of the network. Furthermore, the strongest synchronization within VIN was observed before heartbeat stimulated the cortex, which might be related to the prediction of an afferent heartbeat signal, thus supporting an interoceptive coding framework. Based on our results, the heartbeat is processed at the network level, and this result provides a useful framework that may potentially explain previous results of the regional level HER modulation through network-level processing.\n\nSignificance statementThe resting-state network is composed of several networks supporting different functions. However, although the heartbeat is processed in the cortical regions, even in the resting state, the network supporting this function is unknown. Thus, we identified and investigated the heartbeat-evoked network (HEN), a network composed of significantly increased theta-phase synchronization between cortical regions after a heartbeat. The HEN comprised three modules. In particularly, the visceromotor-interoceptive network was likely to play a major role in network-level heartbeat processing and displayed the strongest synchronization immediately before the heartbeat enters the CNS, which supports an interoceptive predictive coding framework. These results provide a novel framework that may improve our understanding of cortical heartbeat processing from a network perspective.

neuroscience↗

bioRxiv2017

Heartfelt Face Perception via the Interoceptive Pathway - a MEG study

The somatic marker hypothesis proposes that the cortical representation of visceral signals is a crucial component of emotion processing. No previous study has investigated the causal relationships among brain regions that process visceral information during emotional perception. In this magnetoencephalography study of 32 healthy subjects, heartbeat-evoked potentials (HEPs), which reflect the cortical processing of heartbeats, were modulated by the perception of a sad face. The modulation effect was localized to the prefrontal cortices, the globus pallidus, and an interoceptive network including the right anterior insula (RAI) and anterior cingulate cortex (RACC). Importantly, our Granger causality analysis provides the first evidence for increased causal flow of heartbeat information from the RAI to the RACC during sad face perception. Moreover, this HEP modulation effect was neither an artefact nor an effect of visual-evoked potentials. These findings provide important progress in the understanding of brain-body interactions during emotion processing.

neuroscience↗