Biology subjects

Park, J.

Publications and source records attributed to Park, J..

At least 19 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

Clathrin-coated tubules mediate rapid and selective protein absorption by lysosome-rich enterocytes

In the digestive tract of neonatal mammals and in fish, lysosome-rich enterocytes (LREs) internalize dietary proteins and digest them intracellularly within a large lysosomal vacuole. Impaired LRE function leads to growth stunting and poor survival in zebrafish and mice. Previous work has shown that protein uptake relies on a scavenger receptor complex. However, how LREs can internalize proteins rapidly enough to support organismal growth is unclear. Here, using live and electron microscopy and genetic manipulations in zebrafish, we find that LREs contain apical micron-sized clathrin-coated endocytic tubules (ETs) that perform rapid internalization of proteins and other soluble cargoes, while excluding resident apical membrane proteins. Dab2, an endocytic adaptor linking clathrin to scavenger receptors, controls both the biogenesis and function of ETs by recruiting unconventional myosin Myo6 and by influencing dynamin activity. Our findings suggest that continuous pinching of vesicles from ETs allows for rapid, high-capacity internalization of dietary protein.

cell biology↗

bioRxiv2026

Chirality-Driven Photonic PCR Enables Label-Free Genetic Amplification

Photonic polymerase chain reaction (PCR) offers a rapid alternative to conventional thermal cycling for genetic amplification, but current platforms are limited by low photothermal conversion efficiencies and a dependence on bulky fluorescent monitoring systems. Here we report a chirality-driven photonic amplification paradigm that achieves both accelerated nucleic acid replication and direct, label-free detection. By leveraging chiral plasmonic nanoparticles, we exploit their elevated absorption cross-sections to achieve exceptional light-to-heat conversion and rapid thermal relaxation, significantly accelerating heating and cooling rates during cycling. We show that localized chiral near-fields generated by these chiral plasmonic nanoparticles optimize DNA polymerase conformational dynamics, lowering the activation energy barrier for synthesis and boosting amplification efficiency. Furthermore, by tracking the reaction with circular dichroism spectroscopy, we directly monitor the intrinsic chiroptical signature of amplifying DNA, completely eliminating the need for external fluorescent dyes or labeled probes. We validate this system using SARS-CoV-2 E-gene plasmid DNA templates, demonstrating rapid, label-free amplification and single-copy detection within clinically relevant timelines. By bridging asymmetric photothermal dynamics with chiral-field-induced enzymatic activation, this work translates chiroplasmonic materials from fundamental physics into high-performance, point-of-care molecular diagnostics.

bioengineering↗

bioRxiv2026

Genomic foundation models do not yet boost common variant discovery beyond standard functional annotations

Genomic foundation models (GFMs) use large-scale AI to model genetic sequences and their influence on molecular phenotypes. While GFMs have shown promise in rare variant analysis, their utility for common variant discovery remains untested. Using the surrogate functional false discovery rate framework for functionally informed GWAS discovery, we compared standard functional annotations (baselineLD) with annotations derived from three leading GFMs: the sequence-to-function models AlphaGenome and Borzoi, and the genomic language model GPN-Star. Across 27 UK Biobank traits, GPN-Star decreased locus discovery relative to a standard GWAS, whereas AlphaGenome and Borzoi increased discovery but by less than baselineLD (medians 1.8%, 3.8%, and 5.1%). When we combined the GFM and baselineLD annotations, there was no increase over baselineLD alone (median changes -0.1% to 0.2%), suggesting that AlphaGenome and Borzoi mostly capture information already in baselineLD. Thus, GFMs may require larger corpora or trait-specific feature engineering to improve discovery beyond standard functional annotations.

genomics↗

bioRxiv2026

Source-Decomposed Multimodal Graph Connectivity: A Temporal Mixture-Manifold Pipeline for Tracking Ischemic Injury and Treatment

To capture the complex, dynamic network reorganization following acute focal brain injuries that standard static or unimodal neuroimaging frameworks routinely miss, we present an open, reproducible computational multimodal pipeline that integrates resting state functional MRI and diffusion tensor imaging (DTI) into dynamic, source-decomposed graph networks. This framework preserves sub-voxel, multi-peak distributional dynamics over time by modeling regional blood-oxygen-level-dependent signals within sliding windows using a Gaussian mixture model, with model complexity dynamically optimized. The resulting pairwise similarities define time-varying edge weights across local, nonlocal, and DTI-supported structural sources, unifying them into a multimodal connectivity manifold that precisely quantifies node strength, topological turnover, and boundary modifications. Applied to a non-human primate model of photothrombotic ischemia, the methodology revealed severe post-injury disruptions, with 66 of 144 nodes (45.8%) fundamentally altering their connectivity across localized sources. Furthermore, coupling this architecture with an Ensemble Kalman Filter (EnKF) allowed for the continuous tracking of a tissue reversibility coordinate, yielding earlier detection of metabolic state collapse than uni-modal baselines and generating a forecast-divergence index as a rigorous early-warning signal. Extended across post-injury treatment boundaries to evaluate network recovery toward baseline, this interpretable, modality-aware framework establishes a standardized, shareable methodological foundation for tracking complex pathophysiological dynamics in neuroinformatics research.

neuroscience↗

bioRxiv2026

Inter-Individual Variability in Cycling Biomechanics During Experimentally Induced Movement-Evoked Knee Pain

Knee pain can alter lower-limb loading and contribute to inter-limb asymmetry, affecting movement mechanics and rehabilitation. Although cycling is frequently prescribed during rehabilitation, the effects of pain on bilateral cycling biomechanics remain poorly understood. This study investigated experimentally induced movement-evoked knee pain on bilateral torque and power output, inter-limb asymmetry, and inter-individual motor responses during cycling. Twenty-three healthy adults (14M and 9F) completed an incremental cycling test followed by eight randomized constant-load trials under pain and no-pain conditions at two intensities. A custom closed-loop torque-dependent electrical stimulation system induced movement-evoked knee pain during the downstroke while bilateral biomechanics were recorded. At higher intensities, movement-evoked knee pain reduced torque (p=0.026, d=0.566) and power (p=0.010, d=0.657) production in the painful limb and altered the normalized symmetry index (NSI) for power (p=0.005, d=0.659), and torque (p<0.001, d=0.754). At lower intensity, pain-leg power (p=0.154) and torque (p=0.104) did not differ significantly between conditions, although torque NSI indicated greater reliance on the non-pain leg (p=0.017, d=0.538). Despite these group-level responses, substantial inter-individual variability was observed ranging from pronounced unloading to increased pain-leg contribution. These findings demonstrate that movement-evoked knee pain alters cycling mechanical output toward the non-painful limb, with substantial heterogeneity in individual motor responses.

neuroscience↗

bioRxiv2026

Causal contribution of motor-parietal network to conscious kinesthetic perception

Bodily awareness, including the conscious experience of limb movement (kinesthesia), is a fundamental form of human consciousness. Tendon vibration-induced kinesthetic illusions provide a tractable model for probing its neural basis. Although previous studies have reported coactivation of the primary motor cortex (M1), the right inferior parietal lobule (IPL), and the right inferior frontal gyrus (IFG) during illusory movement, their causal contributions to conscious kinesthetic experience remain unclear. Here, we combined functional MRI and regional facilitative dual-site transcranial direct current stimulation (tDCS) to establish a causal link between these cortices and illusory foot movement. fMRI revealed that the M1-IPL network supports kinesthetic illusion elicited by bottom-up sensory processing, whereas the IFG plays a role in top-down monitoring of the kinesthetic experience. Critically, concurrent facilitative dual-site tDCS applied to the M1 and IPL significantly enhanced the subjective strength of the illusion, compared with the sham and concurrent tDCS to the M1 and IFG. This effect was replicated without increasing muscle activity in another tDCS study and exceeded those observed with single-site (M1 or IPL) or concurrent higher-order IPL-IFG tDCS. Our findings provide the first compelling causal evidence that conscious kinesthetic perception can be augmented through coordinated interactions between the modality-specific kinesthetic-motor cortex (M1) and the higher-order right inferior parietal cortex (IPL). This coordinated interaction between modality-specific and higher-order cortical regions underlying conscious kinesthetic perception is consistent with the Global Neuronal Workspace hypothesis. Our findings have therefore extended the applicability of this framework from exteroceptive perception to bodily awareness.

neuroscience↗

bioRxiv2026

Methane oxidation genes are only present in bioaerosols at sites with high methane concentrations

Airborne microorganisms connect Earth's habitats, yet a central question in microbial ecology remains: do airborne communities simply reflect what is released from the surfaces below, or does local environmental context shape them? Methane oxidation offers a tractable test, because methane monooxygenase genes are restricted to defined bacterial lineages and methane is directly measurable. Pairing aerosol and underlying soil or water metagenomes across a 35-fold methane range, we show that these genes were present in every soil and water sample, yet detected in aerosols only above the landfill and dairy farm, and not above the three wetlands. The soil did not predict the air; instead, gene detection tracked local methane availability. Aerosol cell concentrations spanned 1,000 to 1,000,000 cells per cubic metre, and bacterial communities tracked their sources whereas eukaryotes were enriched in spore-dispersing fungi. Predicting what airborne microbiomes carry will therefore require accounting for local environmental context, not passive dispersal alone.

microbiology↗

bioRxiv2026

Lineage tracing reveals asynchronous fate restriction in mouse embryos and stem cell-derived embryo models

How a flexible mammalian embryo gives rise to a reproducible body plan remains unclear, partly because cell lineages cannot be followed continuously in vivo. We combined DNA Typewriter lineage recording with tetraploid complementation to reconstruct high-resolution single-cell genealogies across mouse development and built FateVec, an analysis framework that infers fate-bias dynamics and lineage-associated transcriptional programs from reconstructed phylogenies. Loss of developmental potential proved progressive and asynchronous, with multiple lineages acquiring detectable fate bias before morphological diversification at gastrulation. Within the neural crest, most cells remained multipotent over an extended window, while independent founder clades differed markedly in restriction timing. Extending lineage recording to a stem-cell-derived embryo model revealed that cells with shared transcriptional identities can arise from distinct lineage relationships. We further found embryonic-lineage contributions to extraembryonic-like states, exposing an unexplored lineage plasticity. This lineage-resolved view of embryogenesis reveals that cell identity alone predicts neither developmental ancestry nor the timing of fate restriction.

developmental biology↗

bioRxiv2026

Intrinsic dimensionality of deep learning representations reveals cell death-associated heterogeneity in Parkinsons disease iPSC-derived neurons

As AI is increasingly used to stratify heterogeneous Parkinsons disease, it is essential to determine whether learned representations preserve disease-relevant variation within diagnostic or genetic groups. In iPSC-derived neurons from three familial PD cases, deep learning representations encoded an independent measure of cell death, and their intrinsic dimensionality increased with death burden. Latent dimensionality offers a way to examine heterogeneity before AI-derived clusters are interpreted as disease subtypes.

cell biology↗

bioRxiv2026

WrapEvoFS enables auditable feature compression with regret-constrained representative locking

WrapEvoFS provides a deterministic, auditable rule for choosing one feature set from repeated stochastic searches. It retains candidates within a prespecified development-score gap, selects the most representative set by feature overlap, and records the decision before held-out evaluation. A corrected genetic objective preserves score ordering lost through zero truncation. In a fully nested four-class cancer analysis, all 30 locked signatures met the 0.01 tolerance, and 11 differed from the highest-scoring candidate; every changed selection increased mean feature overlap within the eligible pool. Paired differences in area under the receiver operating characteristic curve against recursive feature elimination with cross-validation all had 95% intervals crossing zero. No selector dominated matched comparisons on feature count and predictive performance, and one-time evaluation of frozen signatures at held-out centers yielded heterogeneous effects. WrapEvoFS standardizes selection within a fixed candidate bank under an empirical score-gap constraint, enabling reproducible reporting of performance, compression, and feature-agreement trade-offs without implying predictive superiority or stability under changes in participant composition.

bioinformatics↗

bioRxiv2026

Serum IgM crosslinks hepatitis B subviral particles into supramolecular immune complexes

Hepatitis B virus (HBV)-infected cells release hepatitis B surface antigen (HBsAg)-rich subviral particles (SVPs) in large excess over infectious virions. SVPs bind antibodies against HBsAg (anti-HBs), including neutralizing antibodies, but the physical products of antibody capture in human blood are uncharacterized. Here we used cryo-electron tomography (cryo-ET) to image HBsAg-enriched serum from a patient with severe acute Hepatitis B and observed three-dimensional assemblies of intact IgM-SVP immune complexes. These associations persisted at a lower particle density and were validated by a spatial-randomization null model. Subtomogram averaging and single-particle cryo-electron microscopy (cryo-EM) identified three serum IgM Fc-core assemblies, IgM-J-CD5L, IgM-J and IgM-J-SC, with cryo-EM maps reaching 2.8 angstrom resolution. Mapping these Fc core assemblies into tomograms revealed full-length IgM engaging individual SVPs through several Fab arms and bridging neighboring particles into immune complex networks containing multiple IgM molecules and SVPs. Thus, serum IgM uses multivalent Fab interactions to crosslink HBsAg-rich SVPs into supramolecular immune complexes. This observation extends the SVP decoy model from passive antibody sequestration to higher-order particle organization.

molecular biology↗

bioRxiv2026

Age-Adjusted Cerebellar Volumetry and Developmental Outcomes in Extremely Low Birth Weight Infants

Background: Infants with extremely low birth weight (ELBW) are at high risk for neurodevelopmental impairment, but the relationship between cerebellar structure and later developmental outcome remains incompletely defined. Methods: In this retrospective single-center study, we examined total cerebellar volume on clinically acquired brain magnetic resonance imaging (MRI) in ELBW infants while accounting for postmenstrual age (PMA) at imaging. Results: Of 65 infants screened, 42 were included. Mean gestational age at birth was 25.54 {+/-} 1.68 weeks, mean birth weight was 733.2 {+/-} 118.7 g, and mean PMA at MRI was 43.02 {+/-} 6.53 weeks (range, 31.57--68.00). Mean cerebellar volume was 22.17 {+/-} 9.63 cm. Independently adjudicated developmental outcomes comprised normal development in 16 infants, isolated or specific impairment in 12, and moderate/severe impairment in 14. Unadjusted cerebellar volumes did not differ across developmental groups (P = 0.490) or qualitative MRI categories (P = 0.875). However, the PMA-by-developmental-category interaction was significant (P = 0.002), with estimated cross-sectional slopes of 1.72, 1.56, and 0.39 cm per week, respectively. The interaction remained significant within 36--46 weeks PMA (n = 29; P = 0.011) and after adjustment for small-for-gestational-age (SGA) status. Sensitivity analyses indicated uncertainty in the stability of the interaction. Conclusions: These findings suggest that age-informed cerebellar volumetric patterns may provide developmental information not evident from average volumes alone and support prospective validation with standardized imaging and developmental assessments. As a result, cerebellar volumes obtained early in life may hold prognostic information for ELBW infants.

neuroscience↗

bioRxiv2026

Simulated microgravity induces aging phenotypes in human organoids

Simulated microgravity provides a controlled perturbation for testing how loss of mechanical load affects human tissues. After 24 hours in rotating-wall vessels, neural, cardiac and tonsil organoids developed tissue-specific transcriptional responses that overlapped published spaceflight datasets, accompanied by higher transcriptomic-age estimates in neural and cardiac models, altered cardiac-organoid contraction dynamics and modified tonsil-organoid antiviral gene-expression signatures. These findings establish a multi-organoid framework for studying acute responses to gravitational unloading.

molecular biology↗

bioRxiv2026

Self-guided search in immersive VR reveals active hierarchical planning

Despite the ubiquitous nature of visual search in our daily lives, our knowledge of the underlying mechanisms is almost entirely derived from studies using simple, synthetic stimuli briefly flashed on a computer monitor. In real life, however, visual search occurs in three-dimensional environments over much longer timescales and involves the dynamic coordination of attention, memory, and action planning, generating novel predictions that cannot be tested with traditional approaches. Here, we examined how self-guided visual search unfolds under naturalistic conditions that extend over space and time. We asked participants (N=80) to find specific objects (e.g., a green lamp, an orange shelf) in an immersive, visually rich virtual reality environment using range-limited teleportation (2 m steps). Consistent with our hypotheses, we found that self-guided search engaged a hierarchical information-seeking policy characterized at each stage by recurring plan-and-execute cycles paired with subgoal-specific attentional priorities. Subgoal priorities progressed from wayfinding to identification of clusters of target-similar objects, and then to specific target features. These search priorities progressively narrowed the search space through coordinated eye, head, and body movements that recurred throughout the task. We conclude that naturalistic search is hierarchical, built from sequential subgoals with shifting attentional priorities that single-level tasks cannot capture. Moreover, immersive VR with eye-head-body tracking dissociates motor planning from execution moments and reveals how looking content shifts with each task subgoal while the person moves through space, something desktop tasks cannot capture.

animal behavior and cognition↗

bioRxiv2026

Rac1 and CHK1 Converge on Abi-1 to Regulate DNA Repair Dependency and Treatment Response in Human Cancers

Radiation therapy (RT) resistance remains a major clinical challenge, yet biomarkers guiding precision radiosensitization are lacking. We previously demonstrated that Rac1 promotes RT resistance in glioblastoma (GBM) by inducing Abi-1-S323 dephosphorylation and enhancing non-homologous end joining (NHEJ). Here, we identify Abi-1-S323 as a key regulator of DNA repair states and a determinant of therapeutic efficacy in human cancers. Clinically, loss of Abi-1-S323 phosphorylation was associated with poor outcomes in patients with RT-treated GBM. Bioinformatic analyses revealed that non-small cell lung cancer (NSCLC) and head and neck cancer (HNC) are among the cancers with frequent RAC1 amplification, suggesting that these tumor types may have increased Rac1-Abi-1 signaling activity. Loss of Abi-1-S323 phosphorylation also predicted poor outcomes in patients with RT-treated HNC. Consistent with these clinical observations, high Rac1 activity and low Abi-1-S323 phosphorylation were associated with enhanced DNA double-strand break repair and radioresistance in NSCLC and HNC models, whereas genetic or pharmacological inhibition of this signaling impaired DNA repair and radiosensitized tumors in vitro and in vivo. Mechanistically, we identified CHK1 as a kinase that phosphorylates Abi-1 at S323 and defines an alternative homologous recombination (HR)-dependent repair state. Tumors with high Rac1-Abi-1 signaling exhibited elevated NHEJ capacity and were selectively radiosensitized by Rac1 inhibition, whereas tumors with low Rac1-Abi-1 signaling displayed high CHK1 activity, preferentially relied on HR, and were selectively radiosensitized by CHK1 inhibition. These findings establish Abi-1-S323 as a biomarker defining therapeutically distinct DNA repair states and provide a framework for precision radiosensitization.

cancer biology↗

bioRxiv2026

Brain-to-brain synchrony during shared reminiscing predicts connection and memory in romantic couples

Romantic partners often revisit relationship-defining memories together, reconstructing a shared account of their relationship through conversation. Such shared reminiscing can strengthen interpersonal connection by fostering alignment in thoughts, feelings, and perspectives, an experience known as shared reality. Here, we used functional near-infrared spectroscopy to record brain activity simultaneously from romantic couples during naturalistic, face-to-face conversations. Couples first discussed an unresolved conflict and then jointly recounted their relationship origin story, including how they first met and how their relationship developed. Shared reality decreased following the conflict discussion and returned to baseline levels after the origin story. While recounting their origin story, partners exhibited synchronized activity in the right medial frontopolar cortex, a region implicated in autobiographical memory and reasoning about close others. This synchrony was not observed at rest or during the conflict discussion. Greater medial frontopolar synchrony between partners during the origin story discussion was associated with higher post-conversation shared reality, closeness, and relationship satisfaction, even after accounting for baseline relationship quality. It also predicted better subsequent memory for the conversation, an association that was robust to controlling for the importance and familiarity of the memories being discussed. Together, these findings reveal how the interbrain alignment that emerges during shared reminiscing tracks both the connection partners experience and what they later remember. Our work bridges relationship science and social neuroscience through the naturalistic neuroimaging of live social interaction, and offers a window into the neural processes that accompany mutual understanding, social connection, and sharing memories in romantic relationships.

neuroscience↗

bioRxiv2026

Human iPSCs and iPSC-Derived Endothelial Cells from PAD Patients and Healthy Donors Exhibit Comparable Characteristics and Potency: Implications for Autologous Cell Therapy in Peripheral Artery Disease

BACKGROUND: Peripheral artery disease (PAD) can lead to amputation in advanced cases, making cell therapy using human induced pluripotent stem cells (hiPSCs) a promising therapeutic option. hiPSC-derived endothelial cells (hiPSC-ECs) have shown favorable effects in treating experimental ischemic cardiovascular disease. An autologous approach for PAD patients is preferable to avoid immunological reactions. However, it is yet unknown whether hiPSCs and hiPSC-ECs derived from PAD patients have similar characteristics and potency compared to those derived from non-PAD donors. Therefore, we explored whether there are significant differences in the characteristics and potency of hiPSCs and hiPSC-ECs between non-PAD donors and PAD patients. METHODS: We generated hiPSCs from the blood of non-PAD donors and patients with PAD. We determined the pluripotency of hiPSCs using qRT-PCR, flow cytometry, immunostaining, RNA-seq, and teratoma formation assay. The genetic stability of hiPSCs was confirmed by G-banding karyotyping. We then differentiated hiPSCs into endothelial cells (ECs) in a clinically compatible manner. We compared the characteristics and therapeutic potency of hiPSC-ECs derived from non-PAD and PAD groups using qRT-PCR, flow cytometry, immunostaining, and RNA-seq. In vitro endothelial functions were determined by nitric oxide (NO) production and capillary network formation. Therapeutic potency and incorporation of engrafted hiPSC-ECs were evaluated in a hindlimb ischemia model. RESULTS: We successfully generated hiPSCs from the blood of seven non-PAD donors and eight PAD patients. Both non-PAD and PAD-derived hiPSCs exhibited similar expression levels of pluripotency markers. All hiPSCs, regardless of the group, formed teratomas and showed normal karyotypes. RNA-seq analyses revealed similar gene expression profiles between the groups. hiPSC-ECs derived from both non-PAD and PAD donors exhibited similar expression levels of EC markers at both the gene and protein levels. RNA-seq analyses showed no significant overall differences in gene expression profiles between the groups. Functional analyses demonstrated similar endothelial characteristics and function in hiPSC-ECs from both groups. Both groups showed similar perfusion recovery, limb salvage, and vessel-forming capacity. Engrafted hiPSC-ECs from both groups also exhibited similar angiogenic and vessel-forming capabilities. CONCLUSIONS: Our study demonstrated no significant differences in hiPSCs and hiPSC-ECs derived from non-PAD donors and PAD patients in terms of molecular and cell biological characteristics, therapeutic effects, and vessel-forming capability. Our study indicates that hiPSCs and hiPSC-ECs derived from PAD patients can serve as a novel platform for autologous cell therapy.

cell biology↗