Biology subjects

Suh, D.

Publications and source records attributed to Suh, D..

10 recordsLinked to original sources

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

CMAC: A deep learning framework for absolute cardiomyocyte transcriptional age estimation

Cardiomyocyte maturation spans embryogenesis through postnatal life and involves coordinated transcriptional transitions that are disrupted in disease and incompletely recapitulated by stem cell-derived cardiomyocytes. However, no unified framework exists for assigning absolute transcriptional maturation age across datasets, platforms, and experimental conditions. Here, we developed CMAC (Cardiomyocyte Maturation Age Clock), integrating 18 murine single-cell RNA-sequencing datasets spanning embryonic and postnatal timepoints, into a batch-invariant probabilistic atlas using single cell variational inference (scVI) with a 100-dimensional latent representation. Analysis of the developmental trajectory revealed highly non-uniform transcriptional change, with 63.9% of the total transcriptional journey completed by birth and the neonatal transition representing the largest single transcriptional step. An XGBoost regressor trained on the CMAC latent space predicted absolute chronological age with a leave-one-dataset-out mean absolute error (MAE) of 4.09 days (median 3.27 days), Pearson r = 0.903, and Spearman {rho} = 0.908 across 18 datasets and six sequencing platforms, outperforming linear regression (MAE = 6.18 days) and PCA-based representations (MAE = 6.35 days). In an independent P14 cohort comprising 98,163 cardiomyocytes from six biological replicates, CMAC achieved a mouse-level MAE of 0.33 days, with all six mice predicted within 1.1 days of chronological age. Application of CMAC to a previously published PGC1/{beta} double-knockout model with established delayed cardiomyocyte maturation independently recapitulated this phenotype, quantifying maturation deficits of 4.77 to 8.60 days across P7 to P28, with the largest deficit at P14. Together, these results establish CMAC as a quantitative, deep learning framework for assigning absolute transcriptional maturation age and quantifying deviations from normal cardiomyocyte development.

genomics↗

bioRxiv2026

SEME enables programmable transcript reconstruction through synthetic microexon incorporation

Precise correction of pathogenic mutations remains challenging for therapeutic applications because genome editing within protein-coding exons can generate unintended insertion-deletion byproducts that disrupt coding integrity and protein function. To address this limitation, we developed the Spliceable Editable Microexon Element (SEME), an intron-targeting platform that enables programmable microexon incorporation through endogenous splicing. In induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), SEME corrected aberrant splicing caused by the dilated cardiomyopathy-associated FLNC c.2003A>G variant by restoring the five nucleotides missing from exon 12, thereby recovering filamin C expression. Together, these findings establish programmable microexon incorporation as a proof-of-concept strategy for correcting diverse disease-causing transcript defects.

bioengineering↗

bioRxiv2026

Splicing Factor SF3B2 Regulates Cardiomyocyte Calcium Handling Through Alternative Splicing of Cardiac Ion Channel Genes

BackgroundAlternative splicing is a critical determinant of protein diversity in the heart, where it drives the postnatal functional maturation of cardiomyocytes and specifies the ion-channel and calcium-handling isoforms required for mature contractile function; dysregulated splicing programs have in turn been implicated in cardiomyopathies and arrhythmias. However, the splicing regulators that control cardiomyocyte calcium handling remain largely unknown. ObjectiveWe systematically screened 276 splicing factor genes in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to identify regulators of calcium handling, and we selected SF3B2, a core U2 snRNP spliceosome component, for detailed follow-up based on complex-level enrichment and prior identification by Murphy et al. 2021 [1]. MethodsA high-throughput siRNA screen targeting 276 splicing factor genes was performed in hiPSC-CMs using 384-well calcium transient imaging. SF3B2 knockdown was followed by deep bulk RNA-seq analysis (n = 3 per group) for differential gene expression with DESeq2 and alternative splicing quantification with rMATS. RNA immunoprecipitation sequencing (RIP-seq) using an epitope-tagged SF3B2 construct was performed to identify direct mRNA binding targets of SF3B2. ResultsThe screen identified multiple U2 snRNP components, including SF3A2, SF3B1, and SF3B4--as regulators of calcium transient duration. SF3B2 was previously identified as a regulator of contractility in this screen [1], and the enrichment of its complex partners above the significance threshold in the current CTD75 analysis supported its selection for follow-up characterization. SF3B2 knockdown resulted in 2,683 differentially expressed genes (adjusted p < 0.05), with downregulated genes enriched in cell cycle and DNA replication pathways. Alternative splicing analysis revealed significant changes across all five rMATS event types in 36 genes within the cardiac muscle cell action potential involved in contraction gene ontology term (GO:0086002), including calcium channel (CACNA1C, CACNA1D, CACNA2D1), potassium channel (KCNH2, KCNQ1), and sodium channel (SCN5A) genes, although the large number of affected genes is consistent with broad spliceosomal perturbation and a formal enrichment test would be needed to determine whether cardiac action potential genes are preferentially affected. Integration of RIP-seq data (597 SF3B2-enriched transcripts, FDR < 0.05) with splicing analysis identified CACNA2D1, which encodes an auxiliary subunit of L-type calcium channels, as both directly bound by SF3B2 and alternatively spliced upon knockdown. ConclusionThese findings identify SF3B2 as a regulator of cardiomyocyte calcium handling and suggest that SF3B2-dependent missplicing of CACNA2D1 may link core spliceosome function to the splicing programs underlying cardiomyocyte functional maturation. Significance StatementThis study provides the first systematic functional screen of splicing factors in cardiomyocyte calcium handling and identifies SF3B2, a U2 snRNP subunit, as a regulator of cardiac ion channel splicing. Transcriptomic, splicing, and RNA binding data converge on CACNA2D1, identifying a route by which a core splicing factor shapes cardiac contractility, extending cardiac splicing regulation beyond the accessory RBPs studied to date.

developmental biology↗

bioRxiv2026

CHARMM-GUI Covalent Ligand Docker as a Web-based Molecular Docking Platform for Covalent Ligands

Covalent inhibitor research is an emerging topic in drug discovery due to its superior performance in specificity and inhibition effects. While molecular docking is a popular strategy in prediction and assessment of ligand conformations or poses in receptor proteins, covalent ligand docking requires nontrivial preparation efforts, as the ligand structure changes during the covalent complex formation. In order to facilitate molecular docking for covalent ligands, we have developed CHARMM-GUI Covalent Ligand Docker (CGUI-CLD), a new module for covalent ligand docking supported by AutoDock4. CGUI-CLD automates ligand preparation, supports ligand modification, implements docking simulation, and presents results through an intuitive user interface. A knowledge-based library built in CGUI-CLD currently supports 66 warheads and 8 amino acids, which can be used to automate the covalent ligand transformation from a pre-reaction to a post-reaction adduct form seamlessly. Moreover, CHARMM-GUI High-Throughput Simulator is integrated for rapid generation of multiple molecular dynamics simulation systems. CGUI-CLD is expected to significantly reduce a massive workload of covalent ligand docking and advance covalent ligand research. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/738313v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1b79576org.highwire.dtl.DTLVardef@1b579eforg.highwire.dtl.DTLVardef@1584d40org.highwire.dtl.DTLVardef@37bc02_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOAbstract TOCC_FLOATNO C_FIG

biophysics↗

bioRxiv2025

Form and function of actin impacts actin health and aging.

The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of actin structure and function influence lifespan and various hallmarks of aging in Caenorhabditis elegans. Whole-animal and tissue-specific knockdown of actin and key actin-binding proteins (ABPs) - arx-2 (Arp2/3), unc-60 (cofilin), and lev-11 (tropomyosin) - led to premature disruption of filament organization, reduced lifespan, and tissue-specific physiological defects. Bulk and single-nucleus RNA-sequencing revealed that ABP knockdowns elicited a strongly "aged" transcriptome. Actin dysfunction broadly exacerbated many age-associated phenotypes, including mitochondrial dysfunction, lipid dysregulation, loss of proteostasis, impaired autophagy, and intestinal barrier failure. Pharmacological destabilization with Latrunculin A mirrored genetic knockdowns, while mild stabilization with Jasplakinolide modestly extended lifespan, emphasizing that optimal and finely-tuned actin function is critical for healthy aging. Finally, analysis of human genome-wide association data revealed that common ACTB polymorphisms correlate with differences in age-related decline in gait speed, suggesting evolutionary conservation of actins role in healthy aging. Taken together, our results provide a comprehensive and publicly accessible resource that maps, for the first time, how actin integrity intersects with diverse aging pathways across tissues and scales. This descriptive framework is intended to enable future mechanistic discovery by offering a deep, unbiased dataset that can be integrated with emerging studies to define how actin dynamics contribute to aging.

cell biology↗

bioRxiv2025

Maskless and on-chip LED-array microscope with spatially-varying angle calibration for centimeter-scale phase imaging

On-chip imaging with LED-array-based angled illumination offers a cost-effective approach for large field-of-view (FOV) phase imaging. However, it faces two main challenges: (1) twin-image ambiguity can degrade phase reconstruction. While mask-based modulation can help, it adds system complexity due to fabrication and alignment requirements; and (2) the illumination angle from each LED varies across large FOVs, and can degrade centimeter-scale phase reconstruction without calibration. Here, we present a computational framework to jointly achieve mask-free on-chip phase imaging and adaptive calibration of spatially-varying illumination angles. The sensor FOV is divided into subregions within each of which LED illumination is approximated as planar. LED illumination angles for each subregion are initialized geometrically. Phase retrieval is then performed within each subregion by constraining the reconstruction with a soft optical transparency prior while simultaneously refining angle estimates. Reconstructed phase maps are merged to produce a high-quality, large-FOV phase image. We demonstrate this approach by achieving centimeter-scale on-chip phase imaging (up to 2.7 x 1.7 cm2) with micron-level resolution across various biological tissue sections.

bioengineering↗

bioRxiv2024

A new tuna specimen (Genus Auxis) from the Duho Formation (middle Miocene) of South Korea

A partially preserved caudal vertebrae imprint of a tuna was discovered from the Duho Formation (Miocene) of South Korea. This specimen was assigned to the genus Auxis and represents the second record of fossil Auxis found in South Korea and in the world. We compared the vertebral morphology of the studied specimen to that of currently known species of Auxis, including extinct taxa. However, the specimen could not be assigned to any extant or new species of Auxis due to anatomical differences and a lack of comparability. The discovery of a new specimen of Auxis aligns with theories of high marine biodiversity in the East Sea (Sea of Japan) and its opening in the Early to Middle Miocene. A widely opened East Sea and upwelling activities might have increased the abundance and diversity of large oceanic fishes such as tunas during the deposition of the Duho Formation. The specimen supports paleoenvironmental interpretations of the Duho Formation as pelagic and subtropical. A taphonomic scenario of the specimen was inferred based on the lack of anal pterygiophores and the leaf imprint on the matrix. The specimen would have been exposed for at least a month in a low-energy sedimentary environment at the deep-sea bottom and would have undergone disintegration before being buried.

paleontology↗

bioRxiv2024

Continuous exposure to 60 Hz extremely low frequency electromagnetic field at 10 to 16 mT promotes various human cell proliferation by activating extracellular-signal-regulated kinase

We previously showed that continuous exposure to 60 Hz extremely low-frequency electromagnetic fields (ELF-EMF) at 6 mT promotes cell proliferation. Here, we investigated the cellular effect of 60 Hz ELF-EMF at over 10 mT. We revised the ELF-EMF-generating device to increase the magnetic flux density of the ELF-EMF stably without thermal effect. We investigated the cellular effect of 10-16 mT ELF-EMF on various mammalian cells including human cervical carcinoma HeLa, rat neuroblastoma B103, liver cancer stem cells Huh7 and Hep3B, immortalized normal hepatic cell MIHA, and normal fibroblast IMR-90. Cell proliferation was promoted around 20% or more in all cells through continuous ELF-EMF exposure at 10 and 14 mT for 72 h, compared with the sham exposure group. In the cells whose proliferation was activated by 14 mT ELF-EMF, the MEK-ERK pathway and NF-{kappa}B were activated but not Akt. These cells showed a slight increase in the S phase population in BrdU incorporation and Ki-67 expression. In these cells, intracellular and mitochondrial ROS levels were not changed, and the proliferation-activating cellular effects of ELF-EMF were maintained even when oxidative phosphorylation was interrupted by CCCP. Additionally, no changes in intracellular calcium levels were observed in ELF-EMF-exposed cells and the proliferation-activating cellular effects of ELF-EMF were maintained in the presence of a calcium chelator, BAPTA-AM. These observations suggested that ROS and intracellular calcium do not mediate ELF-EMFs proliferation-activating physiological effect. Altogether, we demonstrated that 60 Hz ELF-EMF at 10 to 14 mT promotes cell proliferation by activating ERK1/2 and does not affect intracellular ROS and calcium levels.

cell biology↗

bioRxiv2023

1.7 GHz long-term evolution radiofrequency electromagnetic field with efficient thermal control has no effect on the proliferation of different human cell types

Long-term evolution (LTE) radiofrequency electromagnetic field (RF-EMF) is widely used in communication technologies. As a result, the influence of RF-EMF on biological systems is a major public concern, and its physiological effects remain controversial. In our previous study, we showed that continuous exposure of various human cell types to 1.7 GHz LTE RF-EMF at specific absorption rate (SAR) of 2 W/Kg for 72 h can induce cellular senescence. To understand the precise cellular effects of LTE RF-EMF, we elaborated the 1.7 GHz RF-EMF cell exposure system used in the previous study by replacing the RF signal generator and developing a software-based feedback system to improve the exposure power stability. This refinement of the 1.7 GHz LTE RF-EMF generator facilitated the automatic regulation of RF-EMF exposure, maintaining target power levels within a 3% range and a constant temperature even during the 72-h exposure period. With the improved experimental setup, we examined the effect of continuous exposure to 1.7 GHz LTE RF-EMF at up to SAR of 8 W/Kg of adipose tissue-derived stem cells and Huh7, HeLa, and B103 cells. Surprisingly, the proliferation of all cell types, which displayed different growth rates, did not change significantly compared with that of the unexposed controls. However, when the thermal control system was turned off and the subsequent temperature increase induced by the RF-EMF was not controlled during continuous exposure to SAR of 8 W/Kg LTE RF-EMF, cellular proliferation increased by 35.2% at the maximum. These observations strongly suggest that the cellular effects attributed to 1.7 GHz LTE RF-EMF exposure were primarily due to the induced thermal changes, rather than the RF-EMF exposure itself.

cell biology↗