Biology subjects

Son, H.

Publications and source records attributed to Son, H..

18 recordsLinked to original sources

bioRxiv2026

Transcriptome dissection of the Zeb2-associated network reveals a role for NRPS15 in zearalenone biosynthesis in Fusarium graminearum

Fungal secondary metabolites, including mycotoxins, play important roles in fungal biology and represent major concerns for food and feed safety. Zearalenone (ZEA) is an estrogenic polyketide mycotoxin produced by several Fusarium species, yet the genetic network governing its production remains poorly characterized. Here, we investigated genes associated with ZEA production in Fusarium graminearum using two complementary transcriptomic approaches. Time-resolved transcriptome analysis revealed transcriptional changes preceding detectable ZEA accumulation. Temporal clustering further revealed coordinated changes in primary metabolism, transcriptional regulation, carbohydrate utilization, and stress- and transport-associated pathways during ZEA-inducing cultivation. Genotype-based transcriptome analysis of ZEB2 deletion and overexpression strains subsequently identified Zeb2-responsive genes. Functional screening identified NRPS15, encoding a previously uncharacterized nonribosomal peptide synthetase-like protein adjacent to the ZEA biosynthetic cluster, as an important contributor to ZEA production. Deletion of NRPS15 markedly reduced ZEA production and expression of PKS4, PKS13, ZEB1, and ZEB2. NRPS15 expression did not restore ZEA production in the absence of Zeb2. NRPS15 orthologs were conserved in several ZEA-producing Fusarium species, and deletion of NRPS15 substantially reduced ZEA production in Fusarium culmorum. These findings expand the functional genetic context of ZEA production beyond the canonical four-gene biosynthetic cluster.

molecular biology↗

bioRxiv2026

Boolean Logic-responsive FRET Biosensors via Genetically Encoded Autonomous Compilation

Forster resonance energy transfer (FRET) is commonly used to monitor protein-protein interactions in situ. The high spatiotemporal resolution and facile implementation inside complex molecular environments have spearheaded FRET's widespread adoption in biosensing. Despite these advantages, current FRET biosensors are largely restricted to the detection of the presence/absence of individual inputs and are thus unable to sense several multiplexable inputs simultaneously within complex milieu of biological environments. In this work, we introduce a generalizable strategy to construct genetically encoded protein-based FRET biosensors capable of recognizing multiple inputs following Boolean logic-type (YES/OR/AND) operations. These topologically specified FRET sensors powerfully expand the input capacity in sensing protein-protein interactions while providing a user-programmable platform for monitoring heterogeneous biological activities both in vitro and in living cells.

synthetic biology↗

bioRxiv2026

MyoAssist 1.0: An Open-Source Framework for Neuromechanical Simulation of Physical Human-Device Interaction

Physical human-device interaction is central to many emerging technologies in neurorehabilitation and assistive robotics, but simulation-based research in this area remains fragmented across musculoskeletal models, assistive-device representations, task definitions, and controller-development workflows. This fragmentation limits the accessibility, reproducibility, and extensibility of studies on prostheses, exoskeletons, wearable rehabilitation devices, and related human-device systems. Here we introduce MyoAssist 1.0, an open-source framework for neuromechanical simulation of physical human-device interaction built within the MyoSuite ecosystem. MyoAssist organizes each simulation environment as a composed human-device-task system that combines compatible musculoskeletal, assistive-device, and task-scenario components through a shared composition pipeline. The current release includes 15 assistive-device models spanning gait assistance, upper-body support, manipulation, and seated mobility and supports compatible musculoskeletal models ranging from reduced lower-limb models to a 416-muscle full-body model. These human-device systems can be simulated within the broad task scenarios provided by MyoSuite, while MyoAssist adds locomotion-specific task scenarios with configurable terrain and target-velocity conditions for gait-assistive studies. MyoAssist also provides two complementary controller-development frameworks: a reinforcement-learning framework for training adaptive policies and a controller-optimization framework for tuning structured, interpretable human and device controllers. Both frameworks operate on the same simulation environments and provide standardized evaluation outputs for inspecting, comparing, reusing, and extending learned and structured control strategies. By integrating modular human models, assistive-device models, task scenarios, and training workflows under a shared open-source interface, MyoAssist aims to lower the barrier to reproducible simulation-based research and to support collaborative development of assistive technologies for neurorehabilitation and physical human-device interaction.

bioengineering↗

bioRxiv2026

High-variance phenome database reveals important roles of WD40 proteins in the plant pathogenic fungus Fusarium graminearum

WD40 is a highly conserved protein domain in eukaryotes, playing a critical role in various cellular process. We conducted genome-wide functional analysis of WD40 genes in Fusarium graminearum-a phytopathogenic fungus that causes severe yield loss and mycotoxin contamination in major cereal crops. Comprehensive phenome analysis of 119 WD40 gene deletion mutants across 22 distinct phenotypic traits revealed phenotypic divergence within the phenome, establishing a strong correlation between virulence and sexual reproduction. Notably, 21 core WD40 genes were identified, offering valuable insights into divergent biological processes. Pilot interactome studies of Fgwd101 and Fgwd133 provided further insights into their potential pathobiological functions. Our investigation contributes to broadening our knowledge of the biological mechanisms underlying fungal pathogenesis and may assist in the identification of targets for antifungal agents.

molecular biology↗

bioRxiv2026

Development of host-mimicking legume-based media for robust induction of sporulation in soybean-associated Cercospora species

Cercospora species associated with soybean cause Cercospora leaf spot and purple seed stain, which are major diseases affecting soybean production worldwide and can lead to significant yield and seed quality losses. However, unstable and poor sporulation under laboratory conditions remains a critical challenge, hindering the recovery of genetically homogeneous isolates and the establishment of standardized experimental protocols. These limitations further restrict our understanding of the biology, epidemiology, and pathogenicity of these pathogens. In this study, we developed specialized legume-based culture media derived from soybean and pea tissues to mimic host-associated environmental conditions. We compared the sporulation efficacy of these media with commonly used artificial media, including potato dextrose agar (PDA) and V8 juice agar. Our results demonstrated that legume-based media consistently supported higher levels of sporulation than PDA and V8 across multiple strains, although conidial yields varied depending on the strain and medium concentration. Transcriptional analysis of sporulation-related genes revealed that while abaA, wetA, and steA did not show significant differential expression among media, velB exhibited distinct medium-dependent expression patterns. Further evaluation using additional field isolates confirmed that legume-based media provide a more reliable method for inducing sporulation than PDA. Overall, legume-based media represent a practical and effective approach for promoting sporulation in soybean-associated Cercospora species under laboratory conditions.

microbiology↗

bioRxiv2026

Vagal dopaminergic afferents link interoception to trigeminal pain modulation

The vagus nerve conveys interoceptive information, yet how specific vagal sensory afferents regulate pain remains unclear. Here, we tested whether vagus nerve stimulation (VNS) modulates temporomandibular disorder (TMD)-related pain. In a mouse model of TMD, auricular VNS (aVNS) attenuated temporomandibular joint (TMJ) pain behaviors and suppressed sensitization of trigeminal nociceptors. We identified a subset of vagal sensory afferents with dopaminergic features that was sufficient to mediate these effects, as selective activation of these afferents recapitulated the analgesic actions of aVNS. These findings highlight an underappreciated peripheral interoceptive pathway and provide a mechanistic framework for targeted neuromodulation in chronic craniofacial pain.

neuroscience↗

bioRxiv2026

ULK1 drives NDP52-mediated selective autophagic degradation of MHC-I to promote immune evasion in HPV-positive head and neck cancer

Antigen presentation by major histocompatibility complex class I (MHC-I) is critical for tumor cell killing by CD8+ T cells. Accordingly, tumor cells downregulate MHC-I expression through multiple mechanisms, thereby evading the immune response. Importantly, lower levels of MHC-I are associated with poor responses to immune checkpoint inhibitor therapy. Our recent study has shown that the human papillomavirus (HPV) oncoproteins induce MHC-I protein ubiquitination by membrane-associated Ring-CH-type finger 8 (MARCHF8) in HPV-positive head and neck cancer (HPV+ HNC). However, the mechanism by which ubiquitinated MHC-I is degraded remains elusive. By performing genome-wide CRISPR screens, we identified components of the ULK1 and PIK3C3 complexes for autophagy initiation complexes among the top negative regulators of cell-surface MHC-I expression in HPV+ HNC cells. We show that MHC-I is recruited from the ER to autophagosomes by the cargo receptor NDP52, decreasing MHC-I levels. Further, inhibiting the initiation or nucleation steps of autophagy before autophagosome formation is critical for restoring MHC-I levels on the cell surface. Finally, genetic inhibition of autophagy initiation suppresses HPV+ HNC tumor growth in vivo and enhances the CD8+ T cell-mediated antitumor response. Our findings suggest that autophagic degradation of MARCHF8-ubiquitinated MHC-I is a key immune evasion mechanism in HPV+ HNC.

cancer biology↗

bioRxiv2025

A foundation model for microbial growth dynamics

Microbial growth dynamics contain rich information about microbial populations, which support applications from antibiotic testing to microbiome engineering. However, the high dimensionality of growth data and the scarcity of large, task-specific datasets have limited generalizable modeling analysis across systems. Here, we develop a foundation model for microbial growth dynamics. It is a large-scale, self-supervised representation model trained on [~]370,000 experimental and simulated growth curves spanning diverse microbial species, environmental conditions, and community contexts. The model learns lower-dimensional latent embeddings that capture essential dynamical features of raw growth data and enable accurate reconstruction of these data. The concise representations enhance predictive performance in diverse downstream applications. Using these embedding, we achieve few-shot learning for antibiotic classification and concentration prediction, accurate forecasting of simulated and experimental communities, and inference of total abundance from relative-abundance data. By extracting transferable representations from heterogeneous datasets, our model provides a general framework for analyzing and predicting microbial community dynamics from limited measurements.

synthetic biology↗

bioRxiv2025

Transposon-plasmid nesting enables fast response to fluctuating environments

Mobile genetic elements (MGEs) play a critical role in shaping the response and evolution of microbial populations and communities. Despite distinct maintenance mechanisms, different types of MGEs can form nested structures. Using bioinformatics analysis of 14,338 plasmids in the NCBI RefSeq database, we found transposons to be widespread and significantly enriched on plasmids relative to chromosomes, highlighting the prevalence of transposon-plasmid nesting. We hypothesized that this nested structure provides unique adaptive advantages by combining transposition-driven genetic mobility with plasmid-mediated copy number amplification. Using engineered transposon systems, we demonstrated that nesting enables rapid and tunable responses of transposon-encoded genes in fluctuating environments. Specifically, transposition maintains a reservoir of the encoded genes, while plasmid copy number fluctuations further amplify the dynamic range of gene dosage, thus enhancing the response speed and stability of transposon-encoded traits. Our findings demonstrate an adaptive benefit of transposon-plasmid nesting and provide insights into their ecological persistence and evolutionary success.

systems biology↗

bioRxiv2024

Forced mouth opening induces post-traumatic hyperalgesia and associated peripheral sensitization after temporomandibular joints injury in mice

Temporomandibular disorder (TMD) is the most prevalent painful condition in the craniofacial area. The pathophysiology of TMD is not fully understood, and it is necessary to understand pathophysiology underlying painful TMD conditions to develop more effective treatment methods. Recent studies suggested that external or intrinsic trauma to TMJ is associated with chronic TMD in patients. Here, we investigated the effects of the TMJ trauma through forced-mouth opening (FMO) in mice to determine pain behaviors and peripheral sensitization of trigeminal nociceptors. FMO increased mechanical hyperalgesia assessed by von Frey test, spontaneous pain-like behaviors assessed by mouse grimace scale, and anxiety-like behaviors assessed by open-field test. In vivo GCaMP Ca2+ imaging of intact trigeminal ganglia (TG) showed increased spontaneous Ca2+ activity and mechanical hypersensitivity of TG neurons in the FMO compared to the sham group. Ca2+ responses evoked by cold, heat, and capsaicin stimuli were also increased. FMO-induced hyperalgesia and neuronal hyperactivities were not sex dependent. TG neurons sensitized following FMO were primarily small to medium-sized nociceptive afferents. Consistently, most TMJ afferents in the TG were small-sized peptidergic neurons expressing calcitonin gene-related peptides, whereas nonpeptidergic TMJ afferents were relatively low. FMO-induced intraneural inflammation in the surrounding tissues of the TMJ indicates potentially novel mechanisms of peripheral sensitization following TMJ injury. These results suggest that the TMJ injury leads to persistent post-traumatic hyperalgesia associated with peripheral sensitization of trigeminal nociceptors.

neuroscience↗

bioRxiv2024

Elucidation of neuronal activity in mouse models of TMJ injury by in vivo GCaMP Ca2+ imaging of intact trigeminal ganglion neurons

Patients with temporomandibular disorders (TMD) typically experience facial pain and discomfort or tenderness in the temporomandibular joint (TMJ), causing disability in daily life. Unfortunately, existing treatments for TMD are not always effective, creating a need for more advanced, mechanism-based therapies. In this study, we used in vivo GCaMP3 Ca2+ imaging of intact trigeminal ganglia (TG) to characterize functional activity of the TG neurons in vivo, specifically in TMJ animal models. This system allows us to observe neuronal activity in intact anatomical, physiological, and clinical conditions and to assess neuronal function and response to various stimuli. We observed a significant increase in spontaneously and transiently activated neurons responding to mechanical, thermal, and chemical stimuli in the TG of forced mouth open (FMO) mice. An inhibitor of the CGRP receptor significantly attenuated FMO-induced facial hypersensitivity. In addition, we confirmed the attenuating effect of CGRP antagonist on FMO-induced sensitization by in vivo GCaMP3 Ca2+ imaging of intact TG. Our results contribute to unraveling the role and activity of TG neurons in the TMJ pain animal models of TMD, bringing us closer understanding the pathophysiological processes underlying TMD. Our study also illustrates the utility of in vivo GCaMP3 Ca2+ imaging of intact TG for studies aimed at developing more targeted and effective treatments for TMD.

neuroscience↗

bioRxiv2021

Multi-organ analysis of low-level somatic mosaicism reveals stage- and tissue-specific mutational features in human development

Most somatic mutations arising during normal development present as low-level in single or multiple tissues depending on the developmental stage and affected organs1-4. However, it remains unclear how the human developmental stages or mutation-carrying organs affect somatic mutations features. Here, we performed a systemic and comprehensive analysis of low-level somatic mutations using deep whole-exome sequencing (WES; average read depth: [~]500x) of 498 multiple organ tissues with matched controls from 190 individuals. We found that early-stage mutations shared between multiple organs are lower in number but showed higher allele frequencies than late-stage mutations [0.54 vs. 5.83 variants per individual: 6.17% vs. 1.5% variant allele frequency (VAF)] along with less nonsynonymous mutations and lower functional impacts. Additionally, early- and late-stage mutations had unique mutational signatures distinct from tumor-originate mutations. Compared with early-stage mutations presenting a clock-like signature across all studied organs or tissues, late-stage mutations show organ, tissue, and cell-type specificity in mutation count, VAFs, and mutational signatures. In particular, analysis of brain somatic mutations shows bimodal occurrence and temporal-lobe-specific mutational signatures. These findings provide new insight into the features of somatic mosaicisms dependent on developmental stages and brain regions.

genomics↗

bioRxiv2021

Meclizine and metabotropic glutamate receptor agonists attenuate severe pain and primary sensory neuron Ca2+ activity in chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) affects about 68% of patients undergoing chemotherapy and causes severe neuropathic pain which is debilitating health problem and greatly reduces quality of life. Cisplatin is a commonly used platinum-based chemotherapeutic drug known to cause CIPN, possibly by causing oxidative stress damage to primary sensory neurons. Metabotropic glutamate receptors (mGluRs) are widely hypothesized to be involved in pain processing. Meclizine is an H1 histamine receptor antagonist which is known to have neuroprotective effects including anti-oxidative effect. Here, we used a mouse model of cisplatin-induced CIPN to test agonists of mGluR8 and group II mGluR as well as meclizine as interventions to reduce cisplatin-induced pain. We performed behavioral pain tests and in vivo entire DRG neurons Ca2+ imaging using genetically-encoded Ca2+ indicator, Pirt-GCaMP3 to monitor different drug interventions on a populational ensemble level. CIPN induced increased spontaneous Ca2+ activity in DRG neurons, increased Ca2+ transient amplitudes, and hyperresponses to mechanical, thermal, and chemical stimuli. We found mGluR8 agonist, DCPG, group II mGluR agonist, LY379268, and Histamine1 receptor antagonist, meclizine all significantly attenuated mechanical and thermal pain caused by CIPN. LY379268 and meclizine, but not DCPG, attenuated DRG neuronal Ca2+ activity elevated by CIPN. Furthermore, meclizine attenuated cisplatin-induced weight loss. These results suggest group II mGluR agonist, mGluR8 agonist, and meclizine are excellent candidates to study for mechanisms and new treatment option for CIPN.

neuroscience↗

bioRxiv2021

Capsaicin pretreatment alleviates postoperative pain and reduces primary sensory neuron Ca2+ activity

After surgeries, especially thoracotomy incision, patients develop unbearable pain. Opioids are used for reducing pain but often cause serious side effects. Previously, we found that capsaicin pretreatment of the incision area alleviated spontaneous and thermal pain in a postoperative pain animal model. In the present study, we aimed to monitor primary sensory neuron Ca2+ activity in in vivo dorsal root ganglia (DRG) in a postoperative pain model using Pirt-GCaMP3 treated with capsaicin or controls. Intraplantar injection of capsaicin (0.05%) alleviated spontaneous, mechanical, and thermal postoperative pain. The Ca2+ response in in vivo DRG and in in situ spinal cord was significantly enhanced in the ipsilateral side compared to contralateral side or naive control. Primary sensory nerve fiber length was significantly decreased in the incision skin area in capsaicin-pretreated animals detected by immunohistochemistry and placental alkaline phosphatase (PLAP) staining. Thus, capsaicin pretreatment alleviates postoperative pain by suppressing Ca2+ response due to degeneration of primary sensory nerve fibers in the skin.

neuroscience↗

bioRxiv2021

Mast cell-specific receptor/corticotropin-releasing factor axis regulates alcohol withdrawal-associated headache

Rehabilitation from alcohol addiction or abuse is challenging due to alcohol withdrawal symptoms. Headache is a severe alcohol withdrawal symptom that frequently contributes to rehabilitation failure. Despite the need for treating alcohol withdrawal-induced headache, there is no appropriate therapeutic option available. Development of improved therapeutics will depend on obtaining a clearer understanding of alcohol withdrawal-induced headache pain mechanisms. Here, we show that the mast cell-specific receptor MrgprB2 controls development of alcohol withdrawal-induced headache. Withdrawing alcohol from alcohol-acclimated mice induces strong headache behaviors, including facial allodynia, facial pain expressions, and reduced walking movement, symptoms often observed in humans suffering from headache. Observed pain behaviors were abolished in MrgprB2-deficient mice. We observed in vivo spontaneous activation and hypersensitization of trigeminal ganglia neurons in alcohol withdrawal mice, but not in MrgprB2-deficient mice. Corticotropin-releasing factor (CRF) was increased in dura mater after alcohol withdrawal. Injection of CRF into dura mater resulted in activation of trigeminal ganglia neurons and vasodilation, which was accompanied by headache behavior. In cells, CRF evoked Ca2+ transients via MrgprB2 or human MrgprX2. The results indicate that alcohol withdrawal causes headache via mast cell degranulation in dura mater. The process is under control of MrgprB2/MrgprX2, which would appear to represent a potential target for treating alcohol withdrawal-related headache.

neuroscience↗

bioRxiv2021

Imaging sensory transmission and neuronal plasticity in primary sensory neurons with genetically-encoded voltage indicators

Detection of somatosensory inputs requires conversion of external stimuli into electrical signals by activation of primary sensory neurons. The mechanisms by which heterogeneous primary sensory neurons encode different somatosensory inputs remains unclear. In vivo dorsal root ganglia (DRG) imaging using genetically-encoded Ca2+ indicators (GECIs) is currently the best technique for this purpose by providing an unprecedented spatial and populational resolution. It permits the simultaneous imaging of >1800 neurons/DRG in live mice. However, this approach is not ideal given that Ca2+ is a second messenger and has inherently slow response kinetics. In contrast, genetically-encoded voltage indicators (GEVIs) have the potential to track voltage changes in multiple neurons in real time but often lack the brightness and dynamic range required for in vivo use. Here, we used soma-targeted ASAP4.4-Kv, a novel GEVI, to dissect the temporal dynamics of noxious and non-noxious neuronal signals during mechanical, thermal, or chemical stimulation in DRG of live mice. ASAP4.4-Kv is sufficiently bright and fast enough to optically characterize individual neuron coding dynamics. Notably, using ASAP4.4-Kv, we uncovered cell-to-cell electrical synchronization between adjacent DRG neurons and robust dynamic transformations in sensory coding following tissue injury. Finally, we found that a combination of GEVI and GECI imaging empowered in vivo optical studies of sensory signal processing and integration mechanisms with optimal spatiotemporal analysis. HighlightsO_LIIn vivo ultra fast and sensitive dynamic voltage imaging of peripheral primary sensory neurons by a newly generated genetically-encoded voltage indicator. C_LIO_LIIdentification of mechanical, thermal, or chemical stimuli-evoked voltage signals with superior temporal resolution. C_LIO_LISingle-cell detection of changes in sub- and suprathreshold voltage dynamics across different disease conditions. C_LIO_LICombination of voltage (by ASAP4.4-Kv) and Ca2+ (by Pirt-GCaMP3) signals to facilitate the understanding of signal processing and integration of primary sensory neurons, especially for noxious versus non-noxious sensation. C_LI

neuroscience↗

bioRxiv2020

Although host-related factors are important for the formation of gut microbiota, environmental factors cannot be ignored

The gut microbiome is essential to human health. However, little is known about the influence of the environment versus host-related factors (e.g. genetic background, sex, age, and body mass) in the formation of human intestinal microflora. Here, we present evidence in support of the importance of host-related factors in the establishment and maintenance of individual gut assemblages. We collected fecal samples (n = 249) from 44 Korean naval trainees and 39 healthy people living in Korea over eight weeks and sequenced the bacterial 16S rRNA genes. The following hypotheses were tested: 1) microbiome function is linked to its diversity, community structure, and genetic host-related factors, and 2) preexisting host-related factors have a more significant effect on gut microbiome formation and composition than environmental factors. For each individual, the difference between the initial gut microbiota and that after eight weeks was negligible even though the 44 naval trainees lived in the same area and received the same diet, the same amount of exercise, and the same amount of physical stress during the study. This suggests that host-related factors, rather than environmental factors, is a key determinant of individual gut microflora. Moreover, eight weeks of physical training and experiencing the same environmental conditions resulted in an increase in the species Bifidobacterium, Faecalibacterium, and Roseburia in most trainees, suggesting a healthier intestinal environment. IMPORTANCEIn order to understand the role of human gut microbiome, it is important to know how individuals gut microbiota are formed. In this study, we tested the host-related factors versus environmental factors to affect gut microbiome and found that the former have a more association. However, we also found that the controlled environment give an effect on the gut microflora as well. This study provides preliminary evidence that differences in the formation and diversity of gut microbiota within a population could be determined by host-related factors rather than environmental factors.

microbiology↗

bioRxiv2017

Accurate detection of low-level somatic mutations with technical replication for next-generation sequencing

Accurate genome-wide detection of somatic mutations with low variant allele frequency (VAF, <1%) has proven difficult, for which generalized, scalable methods are lacking. Herein, we describe a new computational method, called RePlow that we developed to detect low-VAF somatic mutations based on simple, library-level replicates for next-generation sequencing on any platform. Through joint analysis of replicates, RePlow is able to remove prevailing background errors in next-generation sequencing analysis, facilitating remarkable improvement in the detection accuracy for low-VAF somatic mutations (up to [~]99% reduction in false positives). The method was validated in independent cancer panel and brain tissue sequencing data. Our study suggests a new paradigm with which to exploit an overwhelming abundance of sequencing data for accurate variant detection.

genomics↗