Biology subjects

Oh, Y.

Publications and source records attributed to Oh, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

RIG-I-MAVS-NOXA axis coordinates antiviral defense and apoptosis during parahenipavirus infection

The Gamak virus (GAKV) is a recently identified shrew-borne paramyxovirus belonging to the genus Parahenipavirus, which also includes the zoonotic Langya virus (LayV). Despite the growing recognition of shrew-associated paramyxoviruses, the host pathways that detect infection and regulate antiviral responses remain poorly understood. In this study, we characterized host responses to GAKV infection using integrated in vitro and in vivo approaches. GAKV infection induced robust innate immune responses in A549 cells, characterized by activation of interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 1 (STAT1), together with induction of type I interferon (IFN) and interferon-stimulated genes (ISGs). Transcriptomic analysis further revealed coordinated enrichment of antiviral and intrinsic apoptosis-associated pathways, suggesting a link between innate immune signaling and apoptosis during GAKV infection. Genetic analyses identified retinoic acid-inducible gene I (RIG-I) and mitochondrial antiviral signaling protein (MAVS) as essential mediators of antiviral signaling and apoptosis during GAKV infection. Furthermore, disruption of type I IFN-STAT1 signaling attenuated apoptosis. NOXA knockdown reduced apoptosis and enhanced viral replication, identifying NOXA as a downstream effector linking innate immune activation to apoptosis. Consistent with these in vitro findings, intranasal GAKV infection in six-week-old female wild-type BALB/c mice was associated with lung-restricted viral RNA detection and induction of antiviral responses without overt disease. Together, these findings identify a RIG-I-MAVS-IFN-NOXA signaling axis that integrates antiviral and apoptotic responses during GAKV infection, providing a mechanistic framework for understanding host defense against parahenipaviruses.

microbiology↗

bioRxiv2026

Screening Lipid Nanoparticles through Structure-Ratio Alignment

Lipid Nanoparticles (LNPs) are widely used as delivery systems for nucleic acid therapeutics, where transfection efficiency is determined by both the identities of constituent lipid components and their composition ratios. While prior studies have focused on learning molecular representations for individual components, modeling how multiple components and their ratios jointly influence LNP performance remains underexplored. In this work, we propose STRATA, a framework that models molecule interaction between LNP components, which is known to contribute to LNP transfection efficiency. Our approach is built on two complementary views: (1) a ratio-centric view that captures interaction patterns induced by composition ratios through a transformer with a Ratio-induced Positional Embedding, and (2) a molecule-centric view that incorporates interaction-induced effects into structure-based molecule embeddings. By jointly training and aligning these views, our model integrates molecular structure and composition ratio within a unified framework that captures interaction-driven effects. Experiments demonstrate that our method improves prediction accuracy and generalization to unseen molecules and ratios, highlighting the effectiveness of our approach. Implementation code will be available after acceptance.

biochemistry↗

bioRxiv2026

Reproducible and shareable bioinformatics pipelines from natural-language prompts

Large language models (LLMs) are increasingly used to generate bioinformatics pipelines and to carry out analyses from natural-language prompts. However, the resulting analyses are often difficult to reproduce across sessions, owing to the non-deterministic nature of LLM-driven conversations and heterogeneity of local execution environments, and cannot run on remote high-performance computing (HPC) servers or be shared and reused. We present Autopipe, a platform that guides any Model Context Protocol (MCP) - compatible LLM to produce, execute, and publish source-preserved, re-executable containerized pipelines. Autopipe enables users to execute bioinformatics pipelines on any on-premises remote servers - supported by comprehensive setup documentation aimed at researchers without prior server-administration experience - and to visualize results through an extensible web-based viewer. The Autopipe platform comprises four components: a desktop application with an embedded MCP server for pipeline management and remote execution, an online registry for pipeline and plugin discovery, a web-based result viewer, and a CLI tool for customizing viewer plugins. Autopipe turns conversational analysis into re-executable and shareable workflows. Autopipe is freely available at https://autopipe.org/.

bioinformatics↗

bioRxiv2026

AbiOmics: An End-to-End Pipeline to Train Machine Learning Models for Discrimination of Plant Abiotic Stresses Using Transcriptomic Profiling Data

Abiotic stresses are primary constraints on global crop productivity, reducing yields by up to 80%. While traditional phenotypic sensing detects stress only after physiological symptoms emerge and often fails to discriminate specific stressor types, transcriptomic profiling offers a high-dimensional solution, capturing rapid and sensitive molecular shifts. In this study, we developed AbiOmics, the first end-to-end machine learning pipeline specifically designed to identify and discriminate among multiple stressors. This approach represents a previously undocumented method for stress specification using large-scale transcriptomic big data. We identified 320 stress-specific marker genes using a curated collection of 1,243 transcriptomes of Arabidopsis samples treated with four major abiotic stresses, salt, cold, heat, and drought. A single-layer perceptron model trained on these features achieved 91% accuracy during five-fold cross-validation and 93% accuracy on an independent test set. The model demonstrated an unprecedented capacity to generalize to multi-stress conditions, identifying concurrent signatures in combinatorial salt-and-heat treatments. By integrating marker identification with SHAP-based biological interpretation, AbiOmics provides a rigorously validated diagnostic tool superior to conventional sensing. This framework establishes a high-confidence labeling strategy for AI-driven crop management and precision breeding to mitigate climate change impacts. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=73 SRC="FIGDIR/small/707868v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@573cb5org.highwire.dtl.DTLVardef@152a0b0org.highwire.dtl.DTLVardef@1b389a5org.highwire.dtl.DTLVardef@11c60d_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2026

Identification of 4,5,6,7-Tetrabromo-1H-benzotriazole (TBB) as a Small Molecule MESH1 Inhibitor that Suppresses Ferroptosis

Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation and contributes to diverse pathologies including ischemia-reperfusion injury and neurodegenerative disorders. Current ferroptosis inhibitors largely function as nonspecific radical-trapping antioxidants, limiting their clinical utility. We previously identified MESH1 as a key regulator of ferroptosis through its NADPH phosphatase activity. Here, we identify 4,5,6,7-tetrabromo-1H-benzotriazole (TBB) as a small molecule inhibitor of MESH1 with an IC50 value of 4.7 {+/-} 0.3 {micro}M. X-ray crystallography revealed the molecular determinants of TBB recognition which are corroborated through structure-activity relationships of TBB analogs. TBB protected multiple cell lines against ferroptosis in vitro, and this effect was mitigated by MESH1 knockdown, consistent with on-target activity. Furthermore, TBB reduced neuronal death in an ex vivo brain slice model of Alzheimers disease. Collectively, these findings establish TBB as a bona fide small-molecule MESH1 inhibitor that suppresses ferroptosis and establishes MESH1 as a promising therapeutic target. Graphical AbstractDepicting mechanism of TBB suppressing ferroptosis through the inhibition of MESH1. Figure Created with Biorender.com O_FIG O_LINKSMALLFIG WIDTH=131 HEIGHT=200 SRC="FIGDIR/small/706832v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1fd60e9org.highwire.dtl.DTLVardef@1e56518org.highwire.dtl.DTLVardef@15010c2org.highwire.dtl.DTLVardef@17c313a_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2026

The Role of Retinal Flow in Walking

Both visual direction and optic flow have been implicated in walking towards a goal, in experiments that use prisms to alter visual direction. However, prisms bias retinal flow patterns in ways that may affect balance. This will alter foot placement, and indirectly, a walkers path. We used a prism manipulation in virtual reality for goal-directed walking, where we manipulated the location of texture-defined flow as well as direction of gaze. The addition of texture straightened paths, but primarily when it provided flow on the ground plane. Texture only on the ground produced straightening comparable to full-scene texture, whereas wall-only texture produced little straightening. This reveals a disproportionate contribution of motion generated on the ground plane to control locomotion, potentially reflecting higher retinal speeds and the prism-induced rotations in the lower visual field. This suggests that, when visual direction is manipulated by a prism, trajectories might result from unexpected motion patterns that activate a balance response, leading to compensatory foot placement. Thus trajectories may be shaped by complex interactions between goal direction, gaze, and local retinal motion patterns.

neuroscience↗

bioRxiv2025

Stable Inheritance of Transgene and Yellow Fluorescent Protein Gene Expression in Progeny of Transgenic Cacao (Theobroma cacao) Plants

Genetic engineering tools have the potential to rapidly and precisely improve the genome of slow-to-breed cacao. We previously developed an efficient protocol for transforming cacao using cotyledonary explants derived from secondary somatic embryos via Agrobacterium tumefaciens. In this study, we demonstrate that our transformation protocol is successful in elite cultivars, INIAPG-038 and Matina 1-6, producing fertile seeds with stable visual marker inheritance regardless of whether the transgenic plants were used as the pollen or ovule donor. Three vectors were used in the transformations, each containing genes for enhanced yellow fluorescent protein (eyfp) and neomycin phosphotransferase II (nptII). Three transgenic INIAPG-038 events and one transgenic Matina 1-6 event were used to evaluate seed fertility and the stability of transgene inheritance in cacao seeds and plants. The T1 progeny of these four transgenic events were analyzed for YFP expression and transgene presence. YFP expression segregated at a 1:1 ratio in all events when the transgenic plants were crossed with non-transgenic plants, while a 3:1 segregation was observed when transgenic events were crossed with each other. The transgenic plants exhibited a normal phenotype compared to non-transgenic control plants, producing seeds with a 97% germination rate.

plant biology↗

bioRxiv2025

Sex- and ketogenesis-dependent effects of intermittent fasting against diet-induced obesity and fatty liver disease

ABSTRACTSIntermittent fasting (IF) improves metabolic health, yet the requirement for hepatic ketogenesis in mediating these benefits remains unclear. Here, we investigated how hepatic ketogenesis contributes to the metabolic and hepatic effects of IF in male and female mice. In the human liver, ketogenesis-associated genes showed sex-dependent correlations with inflammatory and fibrotic pathways. In mice, fasting increased circulating ketone bodies, with females exhibiting a greater rise, indicating intrinsic sex differences in ketone metabolism. IF reduced body weight and adiposity in both sexes, and these systemic benefits persisted despite antisense oligonucleotide (ASO)-mediated knockdown of hepatic Hmgcs2. In contrast, hepatic benefits were sex- and ketogenesis-dependent. IF markedly reduced steatosis and fibrosis in male mice, but these improvements were attenuated or abolished when hepatic ketogenesis was disrupted. Female mice showed minimal hepatic benefit from IF and displayed heightened susceptibility to steatosis, fibrosis, and inflammatory activation under ketogenic insufficiency. Single-cell transcriptomic analyses identified neutrophils and myofibroblasts as key responders to hepatocyte-derived ketone bodies, and IF suppressed neutrophil-driven inflammatory signaling in a ketogenesis-dependent manner in males but not females. Together, these findings demonstrate that while systemic metabolic improvements from IF are largely ketogenesis-independent, the hepatic anti-steatotic and anti-fibrotic effects of IF are sexually dimorphic and require intact hepatic ketogenesis.

physiology↗

bioRxiv2025

Prion protein-derived cell-penetrating peptide inhibits type II diabetes-associated islet amyloid polypeptide aggregation and cytotoxicity

Islet amyloid polypeptide (IAPP) is a 37-residue peptide hormone co-packaged and co-secreted with insulin by pancreatic {beta}-cells. A pathological hallmark of type II diabetes is the self-assembly of IAPP into {beta}-sheet rich amyloid fibers, which is associated with {beta}-cell impairment. Previously, we showed that a cell-penetrating peptide (CPP) construct, consisting of a hydrophobic signal sequence coupled to a polycationic nuclear localization signal (NLS)-like sequence, exhibited potent anti-prion activity and antagonism of Alzheimers disease-associated amyloid-{beta} (A{beta}) peptide aggregation and neurotoxicity. Here, we have extended this approach towards type II diabetes by assessing the efficacy of the CPP construct, designated as NCAM1-PrP, in inhibiting IAPP oligomerization, fiber formation and associated cytotoxicity. Using complementary in vitro and in silico experiments, we show that NCAM1-PrP effectively modulates IAPPs toxic structures into non-toxic conformations. This study underlines the potential of our designed CPP-based therapeutic approach as a versatile tool in the battle against amyloid-associated pathologies.

biochemistry↗

bioRxiv2025

Conservation and divergence of transcriptional heterogeneity in the cardiac conduction system

The cardiac conduction system (CCS) consists of specialized cardiomyocytes that initiate and propagate electrical activity through the heart. While the transcriptional programs underlying CCS development and function have been studied within individual species, how these programs compare across species and developmental stages remains unclear. Here, we present a comprehensive cross-species and cross-stage analysis of the CCS transcriptome using single-cell/single-nucleus RNA sequencing and spatial transcriptomic datasets from human, mouse, rat, zebrafish, and medaka hearts. We identify shared and species-or stage-specific gene expression patterns, spanning CCS-wide, zonal-, and component-level features, as well as conserved gene regulatory networks across the species. Many conserved genes are associated with human CCS function and related disorders, highlighting their translational relevance for conduction disease. This work refines the molecular characterization of CCS cell types across vertebrates and provides a resource for advancing our understanding of CCS development, function, and pathology.

genomics↗

bioRxiv2025

Optimizing twin prime editing components for scalable genome editing and therapy in spinocerebellar ataxia type 3

Recent advances in prime editing technologies using CRISPR modules fused with reverse transcriptase (RT) have enabled efficient and precise reprogramming of target genomic sequences. Twin prime editing using two coordinated prime editor complexes is a promising strategy for inducing extensive genomic modifications via reverse transcribed complementary templates. However, current twin prime editing systems still require improvements in editing efficiency, accuracy, and intended edit predictability. Here, efficiency and precision of twin prime editing were enhanced via engineering and optimizing conventional SpCas9(H840A)-RT-based prime editor components. A La domain-fused prime editor (La-SpCas9(H840A)-RT) and optimized pegRNAs were developed, achieving a 1.75 {+/-} 0.21-fold increase in gene editing efficiency at multiple genomic loci in human-derived cell lines without increasing off-target activity. La-SpCas9(H840A)-RT facilitated efficient [~]2.8 kb GFP transgene knock-in at target loci and eliminated the expanded polyQ tract in ATXN3 in patient-derived mutant cell lines modeling spinocerebellar ataxia type 3. The advanced twin prime editing platform expands genome engineering capabilities beyond existing CRISPR-based systems and holds great promise for diverse biotechnological and therapeutic applications.

bioengineering↗

bioRxiv2025

In vivo cartography of state-dependent signal flow hierarchy in the human cerebral cortex

Understanding the principle of information flow across distributed brain networks is of paramount importance in neuroscience. Here, we introduce a novel neuroimaging framework, leveraging integrated effective connectivity (iEC) and unconstrained signal flow mapping for data-driven discovery of the human cerebral functional hierarchy. Simulation and empirical validation demonstrated the high fidelity of iEC in recovering connectome directionality and its potential relationship with histologically defined feedforward and feedback pathways. Notably, the iEC-derived hierarchy revealed a monotonically increasing level along the axis where the sensorimotor, association, and paralimbic areas are sequentially ordered - a pattern supported by the Structural Model of laminar connectivity. This hierarchy was further demonstrated to flexibly reorganize across brain states: flattening during an externally oriented condition, evidenced by a reduced slope in the hierarchy, and steepening during an internally focused condition, reflecting heightened engagement of interoceptive regions. Our study highlights the unique role of macroscale directed functional connectivity in uncovering a biologically interpretable state-dependent signal flow hierarchy.

neuroscience↗

bioRxiv2025

EZH1 Q571R-mediated chromatin compaction and its oncogenic potential in thyroid cancer

Dysregulation of Polycomb Repressive Complex 2 (PRC2) is established to contribute to cancer. Of its catalytic subunits, EZH1 and EZH2, EZH2 mutations in cancer have been extensively identified and studied, but the role of EZH1 in cancer remains largely unexplored. The recurrent presence of the EZH1Q571R mutation in follicular thyroid cancer suggests its involvement in tumor progression. Using EZH1 ChIP-seq, ATAC-seq, and H3K27me3 CUT&Tag, we demonstrated that EZH1Q571R enhances chromatin binding and compaction and stimulates PRC2-EZH1 catalytic activity, leading to increased H3K27me3 levels and repression of tumor suppressor genes. Purified PRC2-EZH1Q571R demonstrated a significant increase in histone methyltransferase activity compared to PRC2-EZH1WT via enhanced nucleosome binding and DNA compaction. Notably, this effect is particularly observed with EZH1Q571R but only to a lesser extent with the corresponding EZH2Q570R mutation, highlighting it as an EZH1-specific mechanism. We additionally demonstrated PRC2-EZH1Q571R to efficiently methylate H3K27 in pre-existing H3K36me2/3 nucleosomes, disrupting chromatin homeostasis. Our findings provide key insights into the molecular pathogenesis of EZH1Q571R-driven follicular thyroid cancer.

molecular biology↗

bioRxiv2025

Differential DNA damage response to WRN inhibition identifies a targetable vulnerability in ARID1A-mutated cancers

ARID1A, a key subunit of the SWI/SNF chromatin remodeling complex, is frequently mutated in cancers. However, effective clinical treatments for patients with this mutation are limited, highlighting a demand for new therapeutic strategies. Here, we establish Werner syndrome ATP-dependent helicase (WRN) as a critical vulnerability target in ARID1A-mutated cancers. Upon genetic and pharmacological inhibition of WRN, ARID1A-mutated cells had defective Chk1-mediated DNA damage signaling, resulting in compensatory Chk2 activation, leading to G1-phase arrest and apoptosis, whereas ARID1A-proficient cells underwent Chk1-dependent G2/M arrest. Additional p21 inhibition, combined with WRN suppression, drove G1-arrested cells to re-enter the cell cycle, triggering mitotic catastrophe. The anti-tumor efficacy of WRN inhibition was validated using in vivo cell lines and patient-derived xenograft mouse models. Our findings define WRN as a selective therapeutic target in ARID1A-mutated cancers and suggest a combinatorial strategy of WRN and p21 inhibition as a therapeutic approach.

cancer biology↗

bioRxiv2025

Transgenerational effects of perinatal cannabis exposure on female reproductive parameters in mice

The use of cannabis during pregnancy and nursing is a growing public health concern, and the multigenerational impacts of perinatal cannabis exposure remain largely unknown. To address this knowledge gap, we sought to examine the long-term consequences of perinatal cannabis use on reproductive function and how it might impact subsequent generations. Pregnant female mice were exposed to control vehicle or cannabis extract [25, 100, or 200 mg/ml {Delta}9-tetrahydrocannabinol (THC) in the cannabis extract] from gestational day 1 to postnatal day 21 (twice/day), encompassing the duration of pregnancy through weaning. Based on plasma THC concentrations in F0 females, we chose 100 and 200 mg/ml THC in the cannabis extract for subsequent studies. The selected doses and exposure conditions did not disrupt pregnancy or nursing in F0 females. Pregnancy and neonatal outcomes, including gestational length, litter size, and sexual ratio, were not affected by cannabis exposure. However, cannabis-exposed neonatal F1 pups were smaller. Cannabis exposure delayed vaginal opening as a sign of puberty onset and disrupted estrous cyclicity in F1 females. However, its effects were minor in F2 and F3 females. F1-F3 females showed no abnormal ovarian and uterine histology or plasma estradiol-17{beta} levels and could produce normal offspring without pregnancy issues. These results suggest that the hypothalamus and pituitary are likely perturbed by perinatal cannabis exposure, and the early hypothalamus-pituitary-ovarian axis is disrupted in F1 females. However, they are not sufficient to compromise adult reproductive function. The present results indicate limited transgenerational effects of perinatal cannabis exposure on female reproductive parameters.

pharmacology and toxicology↗

bioRxiv2025

Multiple lesion inductions intensify central sensitization driven by neuroinflammation in a mouse model of endometriosis.

IntroductionEndometriosis is an inflammatory disease associated with chronic pelvic pain (CPP). Growing evidence indicates that endometriotic lesions are not the sole source of pain. Instead, central nervous system (CNS) dysfunction created by prolonged peripheral and central sensitization plays a role in developing endometriosis-associated CPP. This study investigated how CPP is established using a multiple lesion induction mouse model of endometriosis, as repeated retrograde menstruation is considered underlying endometriosis pathogenesis. MethodsWe generated endometriosis-like lesions by injecting endometrial tissue fragments into the peritoneal cavity in mice. The mice received a single (1x) or multiple inductions (6x) to simulate recurrent retrograde menstruation. Lesion development, hyperalgesia by behavioral testing, signs of peripheral sensitization, chronic inflammation, and neuroinflammation were examined with lesions, peritoneal fluids, dorsal root ganglia (DRG), spinal codes, and brain. ResultsMultiple lesion inductions increased lesion numbers and elevated abdominal and hind paw hypersensitivity compared to single induction mice. Elevated persistent glial cell activation across several brain regions and/or spinal cords was found in the multiple induction mice. Specifically, IBA1+ microglial soma size was increased in the hippocampus and thalamus. IBA1+ cells were abundant in the cortex, hippocampus, thalamus, and hypothalamus of the multiple induction mice. GFAP+ astrocytes were mainly elevated in the hippocampus. Elevated TRPV1, SP, and CGRP expressions in the DRG were persistent in the multiple induction mice. Furthermore, multiple inductions induced the severe disappearance of TIM4hi MHCIIlo residential macrophages and the influx of increased proinflammatory TIM4lo MHCIIhi macrophages in the peritoneal cavity. The single and multiple inductions elevated secreted TNF, IL-1{beta}, and IL-6 levels in the peritoneal cavity at 2 weeks. Elevated cytokine levels returned to the pre-induction levels in the single induction mice at 6 weeks; however, they remained elevated in the multiple induction mice. ConclusionsOur results indicate that the repeatedly occurring lesion inductions (=mimic retrograde menstruation) can be a peripheral stimulus that induces nociceptive pain and creates composite chronic inflammatory stimuli to cause neuroinflammation and sensitize the CNS. The circuits of neuroplasticity and stimulation of peripheral organs via a feedback loop of neuroinflammation may mediate widespread endometriosis-associated CPP.

molecular biology↗

bioRxiv2025

Database Permeating through Time, Space, and Medicine: A sequence, structure, and clinical compilation and comparison of transmembrane amino acids in VGL ion channels

Ion channels of the VGL superfamily are extremely diverse in their physiological roles - critical in all excitable cells. Mutations in these channels can cause clinical deficits and symptomologies. With recent advances in sequencing and structural data in the past 30 years, there is a plethora of bioinformatic information that experimentalists can utilize to draw hypotheses about structure and function. However, there is no cohesive database that has compiled this data and presents it in an easily accessible and avoids the confounds of close evolutionary lineages. Here, we seek to fill this gap in resources by compiling and comparing groups of sequences and structures across many channels of the VGL superfamily. Additionally, we corroborate the well-conserved amino acid positions with previous experimental work as well as put forth some understudied but well-conserved amino acid positions that might be fundamental to the certain generalizable mechanisms present in the VGL superfamily channels. To further lend evidence to understudied positions being critical to certain generalizable mechanisms, we also compiled clinical mutation data at these positions across many channels to show the likely functional relevance of these positions. Finally, we will make all of the alignments and resources we generated publicly available at https://github.com/Frank-Yeh-95/VGLDatabaseCompilation for ease of hypothesis generation.

biophysics↗

bioRxiv2024

Local Haplotype Classifiers enable Efficient, Flexible, and Secure Genotype Imputation and Downstream Analyses

The decreasing cost of genotyping technologies led to abundant availability and usage of genetic data. Although it offers many potentials for improving health and curing diseases, genetic data is highly intrusive in many aspects of individual privacy. Secure genotype analysis methods have been developed to perform numerous tasks such as genome-wide association studies, meta-analysis, kinship inference, and genotype imputation outsourcing. Here we present a new approach for using lightweight haplotype classifier models to use predicted haplotype information in a flexible privacy-preserving framework to perform genotype imputation and downstream tasks. Compared to the previous secure methods that rely main on linear models, our approach utilizes efficient models that rely on utilizing haplotypic information, which improves accuracy and increases the throughput of imputation by performing multiple imputations per model evaluation.

bioinformatics↗