Biology subjects

Yoon, D.

Publications and source records attributed to Yoon, D..

16 recordsLinked to original sources

bioRxiv2026

Acute social defeat induces cannabinoid type 1 receptor-dependent synaptic depression in the anterior ventral subiculum to anterior hypothalamic nucleus pathway to drive social avoidance in male mice

BACKGROUND: Social avoidance is a protective response that limits exposure to harmful social stimuli. Although avoidance is a characteristic stress phenotype, its circuit-level regulation remains unclear. The ventral subiculum (vSUB), a major hippocampal output, projects to the anterior hypothalamic nucleus (AHN), a key region for stress responses. METHODS: Male mice underwent acute social defeat stress (ASDS) or subthreshold social defeat stress. We combined social interaction, open field, and elevated plus maze testing with optogenetic-assisted slice recording, pharmacology, pathway-specific chemogenetics and optogenetics, retrograde and anterograde transsynaptic tracing, and in situ hybridization. RESULTS: ASDS induced presynaptic depression at anterior vSUB (avSUB) [->] AHN synapses through a glucocorticoid- and cannabinoid type 1 receptor (CB1R)-dependent mechanism, while posterior vSUB (pvSUB) [->] AHN synapses were unaffected. Infusing a CB1R antagonist into the AHN before ASDS attenuated both the synaptic depression and the social avoidance. Chemogenetic activation of the avSUB [->] AHN pathway during ASDS attenuated social avoidance, whereas its inhibition induced avoidance under subthreshold stress. Optogenetic activation of the avSUB [->] AHN pathway produced an immediate increase in social approach. Anterograde tracing revealed that anterior and posterior vSUB neurons project to largely separate AHN populations. The pvSUB [->] AHN pathway modulates anxiety-like behavior without altering social approach. CONCLUSIONS: These findings reveal specialized roles for vSUB subregions in social and emotional responses, and identify presynaptic gating of the avSUB [->] AHN synapse as a control point for stress-induced social withdrawal.

neuroscience↗

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

Antiviral and anti-inflammatory effects of Tabamide A derivative, TA25, against human rhinovirus and multiple zoonotic viruses in vitro and in silico

Human rhinovirus (HRV), first isolated in 1956, belongs to the family Piconaviridae containing a positive-sense, single-stranded RNA genome. HRV causes mild cold and severe respiratory disease, such as asthma, COPD, and pneumonia. To date, no Food and Drug Administration-approved antiviral or anti-inflammatory drugs are available for HRV. TA25 is a phenolic amide derivative extracted from the leaves of Nicotiana tabacum. To investigate the potential candidate for antiviral therapeutics against zoonotic viruses, we evaluated the antiviral potency of TA25 for HRV and multiple zoonotic viruses. The antiviral and anti-inflammatory effects of TA25 were evaluated using RT-qPCR and RNA-seq. Strand-specific RT-qPCR was performed to measure genomic and anti-genomic RNA expression after TA25 treatment. In addition, an AI-based docking test was conducted to investigate the binding affinity of TA25 with viral target proteins. TA25 induced a significant reduction in viral replication and suppressed the expression of pro-inflammatory genes. Inhibition of viral replication by TA25 treatment was confirmed by strand-specific RT-qPCR. TA25 showed broad-spectrum antiviral activity against multiple viruses, including HRV-1A, Zika virus, Dengue virus, Vaccinia virus, and Influenza B virus Victoria. Using an AI-driven structure-based docking analysis, TA25 showed the strongest binding affinity with the HRV 2B protein. This study demonstrates that TA25 confers the broad antiviral and anti-inflammatory activity against HRV and multiple zoonotic viruses. These findings provide valuable insights into antiviral strategies of TA25 for a promising therapeutic candidate in response to emerging RNA and DNA viruses.

microbiology↗

bioRxiv2025

Computational mechanisms for temporal integration in the anterior claustrum

AbstractThe claustrum, with its extensive reciprocal connections to nearly all cortical regions, has long been hypothesized as a key hub for integrating diverse cognitive, sensory and motor information. However, despite its anatomical connectivity, whether and how it functionally integrates different inputs to generate coherent representations has remained unclear. Here, we developed a recurrent neural network (RNN) trained via supervised learning on behavioral metrics of delayed escape--a behavioral paradigm that requires integration of temporally separated task-relevant signals. A subset of RNN neurons exhibited dynamics similar to those of anterior claustral neurons during this behavior. These neurons formed a recurrent cluster, a structure supported by in vitro stimulation experiments in claustral brain slices. We analyzed the computational properties of this claustrum-like cluster via dimensionality reduction of population activity. The network showed nonlinear integration of temporally distributed inputs and increased synergistic information. Rather than settling into attractors, integrated information was dynamically encoded along continuously evolving neural trajectories. Notably, similar trajectory patterns associated with dynamic integration were observed in claustral recordings, suggesting the models biological plausibility. We propose that the anterior claustrum dynamically integrates task-relevant input signals over time and broadcasts the evolving representation to downstream brain regions capable of reading and interpreting it in a context-dependent manner.

neuroscience↗

bioRxiv2025

Delayed lubricin injection improves cartilage repair tissue quality in an in vivo rabbit osteochondral defect model

Osteochondral lesions (OCL) are common among young patients and often require surgical interventions since cartilage has a poor capacity for self-repair. Bone marrow stimulation (BMS) has been used clinically for decades to treat OCLs, however a persisting challenge with BMS and other cartilage repair strategies is the inferior quality of the resulting fibrocartilaginous repair tissue. Lubrication-based therapies have the potential to improve the quality of cartilage repair tissue as joint lubrication is linked to local cartilage tissue strains and subsequent cellular responses including death and apoptosis. Recently, a full length recombinant human lubricin (rhLubricin) was developed and has been shown to lower friction in cartilage. This study investigated the effect of a single delayed injection of rhLubricin on cartilage repair in an in vivo rabbit OCL model using gross macroscopic evaluation, surface profilometry, histology, and tribology. Moderate improvement in macroscopic scores for cartilage repair were observed. Notably, quantitative analysis of Safranin-O histology showed that rhLubricin treated joints had significantly higher glycosaminoglycan content compared to saline treated joints, and there were no differences in repair integration between groups. Furthermore, rhLubricin treated joints had significantly lower friction coefficients tested across three sliding speeds compared to saline treated joints (rhLubricin: 0.15 {+/-} 0.03 at 0.1 mm/s to 0.12 {+/-} 0.03 at 10 mm/s, Saline: 0.22 {+/-} 0.06 at 0.1 mm/s to 0.19 {+/-} 0.05 at 10 mm/s). Overall, a single delayed injection of rhLubricin improved the quality and lubricating ability of the repair cartilage tissue without inhibiting repair tissue integration.

bioengineering↗

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↗

bioRxiv2024

Self-assembly of microstructured protein coatings with programmable functionality for fluorescent biosensors

Proteins, as genetically programmable functional macromolecules, hold immense potential as biocompatible self-assembling building blocks. Despite their versatility in building coating materials, it has been often hindered from programming their functionality genetically. In this study, we demonstrate a modular self-assembly of protein coatings that are genetically programmable for a biosensor application. We designed recombinant fusion protein building blocks to form microstructured coatings on diverse substrates, such as glass or polymer, through a thermally triggered liquid-liquid phase separation and an orthogonal high-affinity coiled-coil interaction. We incorporated fluorescence proteins into coatings and controlled protein density to enable fluorescence imaging and quantification in a low-resource setting. Then, we created a coating for a calcium biosensor using a genetically engineered calcium indicator protein. This protein coating served as the foundation for our smartphone-based fluorescence biosensor, which successfully measured free calcium concentrations in the millimolar range at which extracellular calcium homeostasis is maintained. Using this fluorescence biosensor, we were able to detect abnormal physiological conditions such as mild or moderate hypercalcemia. We envision that this modular and genetically programmable functional protein coating platform could be extended to the development of highly accessible, low-cost fluorescent biosensors for a variety of targets.

bioengineering↗

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↗

bioRxiv2021

Label-free monitoring of 3D cortical neuronal growth in vitro using optical diffraction tomography

The highly complex central nervous systems of mammals are often studied using three-dimensional (3D) in vitro primary neuronal cultures. A coupled confocal microscopy and immunofluorescence labeling are widely utilized for visualizing the 3D structures of neurons. However, this requires fixation of the neurons and is not suitable for monitoring an identical sample at multiple time points. Thus, we propose a label-free monitoring method for 3D neuronal growth based on refractive index tomograms obtained by optical diffraction tomography. The 3D morphology of the neurons was clearly visualized, and the developmental processes of neurite outgrowth in 3D spaces were analyzed for individual neurons. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/454602v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@b858baorg.highwire.dtl.DTLVardef@c946caorg.highwire.dtl.DTLVardef@468168org.highwire.dtl.DTLVardef@da022c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

MG53 preserves neuromuscular junction integrity and alleviates ALS disease progression

Respiratory failure from progressive respiratory muscle weakness is the most common cause of death in amyotrophic lateral sclerosis (ALS). Defects in neuromuscular junctions (NMJs) and progressive NMJ loss occur at early stages, thus stabilizing and preserving NMJs represents a potential therapeutic strategy to slow ALS disease progression. Here we demonstrate that NMJ damage is repaired by MG53, an intrinsic muscle protein involved in plasma membrane repair. Compromised diaphragm muscle membrane repair and NMJ integrity are early pathological findings in ALS. Diaphragm muscles from ALS mouse models show increased susceptibility to injury and intracellular MG53 aggregation, which is also a hallmark of human muscle samples from ALS patients. We show that systemic administration of recombinant human MG53 protein (rhMG53) in ALS mice protects against injury to diaphragm muscle, preserves NMJ integrity, and slows ALS disease progression. As MG53 is present in circulation in rodents and humans under physiological conditions, our findings provide proof-of-concept data supporting MG53 as a potentially safe and effective therapy to mitigate ALS progression.

cell biology↗

bioRxiv2020

Wild flies hedge their thermal preference bets in response to seasonal fluctuations

Fluctuating environmental pressures can challenge organisms by repeatedly shifting the optimum phenotype. Two contrasting evolutionary strategies to cope with these fluctuations are 1) evolution of the mean phenotype to follow the optimum (adaptive tracking) or 2) diversifying phenotypes so that at least some individuals have high fitness in the current fluctuation (bet-hedging). Bet-hedging could underlie stable differences in the behavior of individuals that are present even when genotype and environment are held constant. Instead of being simply noise, behavioral variation across individuals may reflect an evolutionary strategy of phenotype diversification. Using geographically diverse wild-derived fly strains and high-throughput assays of individual preference, we tested whether thermal preference variation in Drosophila melanogaster could reflect a bet-hedging strategy. We also looked for evidence that populations from different regions differentially adopt bet-hedging or adaptive-tracking strategies. Computational modeling predicted regional differences in the relative advantage of bet-hedging, and we found patterns consistent with that in regional variation in thermal preference heritability. In addition, we found that temporal patterns in mean preference support bet-hedging predictions and that there is a genetic basis for thermal preference variability. Our empirical results point to bet-hedging in thermal preference as a potentially important evolutionary strategy in wild populations.

evolutionary biology↗

bioRxiv2020

Genetic basis of offspring number and body weight variation in Drosophila melanogaster

Drosophila melanogaster egg production, a proxy for fecundity, is an extensively studied life-history trait with a strong genetic basis. As eggs develop into larvae and adults, space and resource constraints can put pressure on the developing offspring, leading to a decrease in viability, body size, and lifespan. Our goal was to map the genetic basis of offspring number and weight under the restriction of a standard laboratory vial. We screened 143 lines from the Drosophila Genetic Reference Panel for offspring numbers and weights to create an offspring index that captured the number vs. weight trade-off. We found 30 associated variants in 18 genes. Validation of hid, Sox21b, CG8312, and mub candidate genes using gene disruption mutants demonstrated a role in adult stage viability, while mutations in Ih and Rbp increased offspring number and increased weight, respectively. The polygenic basis of offspring number and weight, with many variants of small effect, as well as the involvement of genes with varied functional roles, support the notion of Fishers "infinitesimal model" for this life-history trait.

genetics↗

bioRxiv2020

FreeClimber: Automated quantification of climbing performance in Drosophila, with examples from mitonuclear genotypes

Negative geotaxis (climbing) performance is a useful metric for quantifying Drosophila health and vigor. Manual methods to quantify climbing performance are slow, tedious, and may be systematically biased, while available computational methods have inflexible hardware or software requirements. We present an alternative: FreeClimber. This open source, Python-based pipeline subtracts a video’s static background to improve spot detection for moving flies in heterogeneous backgrounds. FreeClimber calculates a cohort’s velocity as the slope of the most linear portion of a mean-vertical position vs. time plot. It can run from a graphical user interface for parameter optimization or a command line interface for high-throughput and automated batch processing. It outputs calculated slopes, spot locations for follow up analyses such as tracking, and several visualizations and diagnostic plots. We demonstrate FreeClimber’s utility in a longitudinal study for endurance exercise performance in Drosophila using six distinct mitochondrial haplotypes paired with a common w1118 nuclear background.Summary statement FreeClimber quantifies the climbing velocity for a group of flies, eliminating systematic biases associated with traditional manual methods in a high throughput and automated (graphical and/or command line-based) platform.List of Symbols and AbbreviationsecceccentricityGUIGraphical User Interfacemito-nuclearMitochondrial-nuclearmitotypesMitochondrial haplotypeOreROregon RROIRegion of InterestyakyakubaZimZimbabwe53View Full Text

bioinformatics↗

bioRxiv2018

Microglial activation in an amyotrophic lateral sclerosis-like model caused by Ranbp2 lossand nucleocytoplasmic transport impairment in retinal ganglion neurons

Nucleocytoplasmic transport is dysregulated in sporadic and familial amyotrophic lateral sclerosis (ALS) and retinal ganglion neurons (RGNs) are purportedly involved in ALS. The Ran-binding protein 2 (Ranbp2) controls rate-limiting steps of nucleocytoplasmic transport. Mice with Ranbp2 loss in Thy1+-motoneurons develop cardinal ALS-like traits, but the impairments in RGNs and the degree of dysfunctional consonance between RGNs and motoneurons caused by Ranbp2 loss are unknown. This understanding will facilitate to discern the role of nucleocytoplasmic transport in the differential vulnerability of neurons to ALS and to develop therapeutic approaches and biomarkers in ALS. Here, we ascertain Ranbp2s function and endophenotypes in RGNs of an ALS-like mouse model lacking Ranbp2 in motoneurons and RGNs. Thy1+-RGNs lacking Ranbp2 shared with motoneurons the dysregulation of nucleocytoplasmic transport. RGN abnormalities were comprised morphologically by soma hypertrophy and optic nerve axonopathy and physiologically by a delay of the visual pathways evoked potentials. Whole-transcriptome analysis showed restricted transcriptional changes in optic nerves that were distinct from those found in sciatic nerves. Specifically, the level and nucleocytoplasmic partition of the anti-apoptotic and novel substrate of Ranbp2, Pttg1/securin, were dysregulated. Further, acetyl-CoA carboxylase 1, which modulates de novo synthesis of fatty acids and T-cell immunity, showed the highest up-regulation (35-fold). This effect was reflected by the activation of ramified Cd11b+ and CD45+-microglia, increase of F4\\80+-microglia and a shift from pseudopodial/lamellipodial to amoeboidal F4\\80+-microglia intermingled between RGNs of naive mice. This immunogenic phenotype was accompanied by the intracellular sequestration in RGNs of metalloproteinase-28, which regulates macrophage recruitment and polarization in inflammation. Ranbp2 genetic insults in RGNs and motoneurons trigger distinct paracrine signaling likely by the dysregulation of nucleocytoplasmic transport of neural-type selective substrates. Metabolic and immune-modulators underpinning RGN-to-microglial signaling are regulated by Ranbp2, and this neuroglial system manifests endophenotypes that are likely useful in the prognosis and diagnosis of ALS.

neuroscience↗

bioRxiv2018

Graphene-oxide quenching-based molecular beacon imaging of exosome-mediated transfer of neurogenic miR-193a on microfluidic platform

A microRNA (miR-193a) was found to be transferred in the exosomes of differentiated neural progenitors to undifferentiated clones. Graphene-oxide (GO) quenching-based molecular beacon was developed to detect RNAs in living cells and tissues quickly and sensitively. Here, we applied GO quencher-based molecular beacon sensor to visualize neurogenic miR-193a levels delivered via exosome during cell-non-autonomous neurogenesis of neural progenitor cells on microfluidic platform. Fluorescence signals of FAM-labeled peptide nucleic acid (PNA) against miR-193a quenched by GO nanosheets (FAM-PNA193a-GO) were recovered in undifferentiated recipient cells differentiated to the neuronal lineage by exosome-mediated neurogenesis 3 days after co-culture with differentiated donor cells. We propose that molecular beacon imaging using PNA-GO complex can be used to visualize individual cellular expression of mature microRNAs revealing their precise spatial localization and temporal sequences by the intercellular exosome delivery of messages to undergo processes such as cell-non-autonomous neurogenesis.

cell biology↗

bioRxiv2017

Co-translational protein targeting facilitates centrosomal recruitment of PCNT during centrosome maturation

As microtubule-organizing centers of animal cells, centrosomes guide the formation of the bipolar spindle that segregates chromosomes during mitosis. At mitosis onset, centrosomes maximize microtubule-organizing activity by rapidly expanding the pericentriolar material (PCM). This process is in part driven by the large PCM protein pericentrin (PCNT), as its level increases at the PCM and helps recruit additional PCM components. However, the mechanism underlying the timely centrosomal enrichment of PCNT remains unclear. Here we show that PCNT is delivered co-translationally to centrosomes during early mitosis by cytoplasmic dynein, as evidenced by centrosomal enrichment of PCNT mRNA, its translation near the centrosome, and requirement of intact polysomes for PCNT mRNA localization. Additionally, the microtubule minus-end regulator, ASPM, is also targeted co-translationally to mitotic spindle poles. Together, these findings suggest that co-translational targeting of cytoplasmic proteins to specific subcellular destinations may be a generalized protein targeting mechanism.

cell biology↗