Biology subjects

Song, J.-H.

Publications and source records attributed to Song, J.-H..

8 recordsLinked to original sources

bioRxiv2026

Long-Lasting Electrohydrodynamically Printed Transparent Soft Microelectrode for Implantable Biointerfaces

Reliable and scalable soft implantable neural interface fabrication remains a key challenge for chronic bioelectronic applications. Here, we present a transparent soft microelectrode fabricated with electrohydrodynamic (EHD) printing, utilizing the fluorinated polymer poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and poly (3, 4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS) to form seamless, selectively patterned multilayer structures with low impedance and long-term stability. Controlled in situ curing during printing yields dense, void-free substrate and encapsulation layers, suppressing interfacial defects and ionic pathways, while maintaining high optical transparency (>60%) with PEDOT:PSS. The printed microelectrodes exhibit low impedance, high charge storage and injection capacities, and stable electrochemical behavior under biomimetic conditions. In addition, the devices demonstrate robust mechanical and electromechanical stability under cyclic deformation in both dry and wet environments, as well as under prolonged electrical stimulation. Accelerated aging studies project multi-year operational lifetimes, and in vitro/in vivo biocompatibility assessments confirm excellent tissue integration. These results establish EHD-printed fluorinated polymer-based microelectrodes as a scalable and durable platform for chronic implantable biointerfaces. ToC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/726391v1_ufig1.gif" ALT="Figure 1"> View larger version (79K): org.highwire.dtl.DTLVardef@f4f717org.highwire.dtl.DTLVardef@8a34a1org.highwire.dtl.DTLVardef@185540dorg.highwire.dtl.DTLVardef@51462a_HPS_FORMAT_FIGEXP M_FIG C_FIG This report presents an electrohydrodynamically printed transparent soft microelectrode for chronic purposes. Electrohydrodynamic printing promotes seamless multilayer structures with selective deposition and long-term mechanical stability. The devices show low impedance, high charge capacity, and robust electrochemical/electromechanical properties. Accelerated aging projects [~]7.2 year lifetimes, and XPS/SEM-EDS confirm strong ion barrier properties and biocompatibility for chronic implantation.

bioengineering↗

bioRxiv2026

Metabolic plasticity of sphingolipids governs cancer cell fitness in acidic tumor ecosystems

Cell state plasticity enables cancer cells to rapidly adapt to fluctuating microenvironments without requiring genetic alteration, shaping tumor evolution under stress. Extracellular acidosis is a persistent feature of solid tumors that impose strong selective pressure, yet how cancer cells maintain fitness under acute and chronic acidic conditions remains unclear. Here, we show that adaptation to acidosis is mediated by plastic rewiring of sphingolipid metabolism centered on ceramide turnover. Spatial multi-omics analysis of three-dimensional tumor models revealed enrichment of ceramides within acidic niches, consistent with a stress-induced phenotype. While acute acidosis promoted ceramide accumulation and reduced fitness, chronic exposure selected for cells capable of dynamically redistributing sphingolipid flux across multiple clearance pathways. Functional perturbation demonstrated that inhibition of individual pathways was insufficient to compromise survival, whereas simultaneous disruption of all ceramide clearance routes resulted in cell death, revealing a degenerate metabolic architecture. This network-level flexibility enables cancer cells to maintain fitness by switching between alternative metabolic states under acidic stress. Together, our findings identify sphingolipid metabolic plasticity as an adaptive strategy that supports tumor persistence in acidic ecosystems and suggest that targeting metabolic flexibility, rather than individual pathways, may provide a more effective therapeutic approach.

cancer biology↗

bioRxiv2025

Metabolic plasticity drives mechanisms of PARP inhibitor persistence in ovarian cancer

PARP inhibitors (PARPi) are the standard maintenance therapy for ovarian cancer, but the frequent emergence of resistance remains a major clinical challenge. Emerging evidence suggests that tumor cell plasticity is an important mechanism enabling this adaptive resistance. In this study, we combined both experimental and computational techniques to model this evolutionary process by long term treatment of the OVCAR3 ovarian cancer cell line with Olaparib (a PARPi). We then performed single-cell RNA sequencing (scRNAseq) on both naive and persistent cells to capture cancer cells heterogenous response. scRNAseq profiling suggested an adaptive metabolic reprogramming in response to long term Olaparib treatment. We then scored single cells for metabolic function, and persister cells were found to have reprogrammed their glutamine metabolism. To test these findings, both persister and naive cells were cultured in glutamine-deprived media and persister cells were found to have higher viability than the naive cells particularly when exposed to Olaparib. To test the cells capacity to switch their metabolic state toward glycolysis, we performed Seahorse mitochondrial and glycolytic stress tests. These analyses revealed that persister cells were less dependent on glutamine metabolism and instead exhibited increased glycolytic capacity compared to naive cells. This metabolic shift resulted in an acquired dependency on glucose, representing a potential therapeutic vulnerability. Together, these results indicate that prolonged Olaparib exposure promotes metabolic plasticity in ovarian cancer cells. To explore how this plasticity might be exploited therapeutically, we developed a proof-of-concept mathematical model that leverages metabolic state transitions to optimize treatment scheduling. ONE SENTENCE SUMMARYOvarian cancer cells exploit metabolic plasticity to increase their evolvability to persist PARP inhibitor treatment.

cancer biology↗

bioRxiv2025

Systematic modulation of sensorimotor learning by domain-specific working memory

People differ in how quickly they learn and adapt sensorimotor skills, and these differences have been linked to individual variation in working memory capacity (WMc). In tasks that can be supported by cognitive strategies, visuospatial WMc has been proposed as a key contributor. However, it remains unclear whether this association reflects domain-specific mechanisms or domain-general executive resources, and whether it extends beyond spatial memory to other visual features. Here, we systematically tested whether domain-specific or domain-general WMc predicts adaptation across three visuomotor adaptation (VMA) tasks known to differentially engage explicit and implicit learning systems. After obtaining independent measures of spatial and feature-based WMc, healthy subjects completed (1) a standard VMA task, which engages both explicit and implicit learning systems; (2) a delayed feedback VMA task, which isolates explicit learning; and (3) a clamped feedback VMA task, which isolates implicit learning. Our results provide converging evidence in support of a domain-specific association between spatial WMc and individual differences in learning. In Experiments 1 and 2, greater spatial WMc was associated with robust increases in explicit learning whereas featured-based WMc was not associated with learning outcomes. Surprisingly, in Experiment 3, greater spatial WMc was associated with reduced implicit learning, suggesting an interaction between latent cognitive capacities and implicit learning not accounted for by traditional models. These results shed light on the precise cognitive mechanisms underlying sensorimotor adaptation and provide novel insight into domain-specific links between spatial WM and motor learning.

neuroscience↗

bioRxiv2024

Human and bats genome robustness under COSMIC mutational signatures

Carcinogenesis is an evolutionary process, and mutations can fix the selected phenotypes in selective microenvironments. Both normal and neoplastic cells are robust to the mutational stressors in the microenvironment to the extent that secure their fitness. To test the robustness of genes under a range of mutagens, we developed a sequential mutation simulator, Sinabro, to simulate single base substitution under a given mutational process. Then, we developed a pipeline to measure the robustness of genes and cells under those mutagenesis processes. We discovered significant human genome robustness to the APOBEC mutational signature SBS2, which is associated with viral defense mechanisms and is implicated in cancer. Robustness evaluations across over 70,000 sequences against 41 signatures showed higher resilience under signatures predominantly causing C-to-T (G-to-A) mutations. Principal component analysis indicates the GC content at the codons wobble position significantly influences robustness, with increased resilience noted under transition mutations compared to transversions. Then, we tested our results in bats at extremes of the lifespan-to-mass relationship and found the long-lived bat is more robust to APOBEC than the short-lived one. By revealing robustness to APOBEC ranked highest in human (and bats with much more than number of APOBEC) genome, this work bolsters the key potential role of APOBECs in aging and cancer, as well as evolved countermeasures to this innate mutagenic process. It also provides the baseline of the human and bat genome robustness under mutational processes associated with aging and cancer. HighlightsO_LISinabro, the sequential mutation simulator, facilitates measuring the robustness of human protein-coding sequences under all COSMIC mutational signatures. C_LIO_LIRobustness under APOBEC mutational signatures showed the largest mean and standard deviation in the human genome. C_LIO_LIRobustness to mutational signatures analysis reveals the role of APOBECs is complementary to cancer in the evolvability of cancer cells in later stages. C_LIO_LIPrincipal component analysis indicates that the GC content at the codons wobble position significantly influences robustness. C_LIO_LIA long-lived bat (Myotis myotis) has higher robustness to APOBECs than a short-lived one (Molossus molossus) than humans. C_LI

genomics↗

bioRxiv2023

Evolvability of cancer-associated genes under APOBEC3A/B selection

Evolvability is an emergent hallmark of cancer that depends on intra-tumor heterogeneity and, ultimately, genetic variation. Mutations generated by APOBEC3 cytidine deaminases can contribute to genetic variation and the consequences of APOBEC activation differ depending on the stage of cancer, with the most significant impact observed during the early stages. However, how APOBEC activity shapes evolutionary patterns of genes in the host genome and differential impacts on cancer-associated and non-cancer genes remain unclear. Analyzing over 40,000 human protein-coding transcripts, we identified distinct distribution patterns of APOBEC3A/B TC motifs between cancer-related genes and controls, suggesting unique associations with cancer. Studying a bat species with many more APOBEC3 genes, we found diverse motif patterns in orthologs of cancer genes compared to controls, similar to humans and suggesting APOBEC evolution to reduce impacts on the genome rather than the converse. Simulations confirmed that APOBEC-induced heterogeneity enhances cancer evolution, shaping clonal dynamics through bimodal introduction of mutations in certain classes of genes. Our results suggest that a major consequence of the bimodal distribution of APOBEC affects greater cancer heterogeneity. HighlightsO_LIUsing a measure of the extent which genes are affected by APOBEC activity, we found that many genes are maximally robust in the human genome. Interestingly, the distribution in the genome of a bat that has many APOBEC genes was similar. C_LIO_LIIn contrast, when analyzing the subset of cancer-associated genes the distribution is bimodal with many genes appearing to susceptible to APOBEC activity. C_LIO_LIAnalysis of orthologs of human genes and other species showed a wide range in the extent to which APOBEC affects genes having the same function. C_LIO_LIThe bimodal distribution of susceptibility to APOBEC drives greater heterogeneity in simulated clonal evolution of cancer. C_LI

cancer biology↗

bioRxiv2021

The role of interspecies recombinations in the evolution of antibiotic resistant pneumococci

AbstractThe evolutionary histories of the antibiotic-resistant Streptococcus pneumoniae lineages PMEN3 and PMEN9 were reconstructed using global collections of genomes. In PMEN3, one resistant clade spread worldwide, and underwent 25 serotype switches, enabling evasion of vaccine-induced immunity. In PMEN9, only 9 switches were detected, and multiple resistant lineages emerged independently and circulated locally. In Germany, PMEN9s expansion correlated significantly with the macrolide:penicillin consumption ratio. These isolates were penicillin sensitive but macrolide resistant, through a homologous recombination that integrated Tn1207.1 into a competence gene, preventing further diversification via transformation. Analysis of a species-wide dataset found 183 acquisitions of macrolide resistance, and multiple gains of the tetracycline-resistant transposon Tn916, through homologous recombination, often originating in other streptococcal species. Consequently, antibiotic selection preserves atypical recom- bination events that cause sequence divergence and structural variation throughout the S. pneumoniae chromosome. These events reveal the genetic exchanges between species normally counter-selected until perturbed by clinical interventions.

genomics↗

bioRxiv2020

Stepwise transmigration cascade of T and B cells through the perivascular channel in lymph node high endothelial venules

High endothelial venules (HEVs) effectively recruit circulating lymphocytes from the blood to lymph nodes. HEVs have endothelial cells (ECs) and perivascular sheaths consisting of fibroblastic reticular cells (FRCs). Many studies have characterized the multiple steps of lymphocyte migration interacting with ECs at the luminal side of HEVs. However, post-luminal migration steps are not well elucidated. Herein, we performed intravital imaging to investigate post-luminal T and B cell migration, consisting of trans-EC migration, crawling in the perivascular channel (a narrow space between ECs and FRCs) and trans-FRC migration. The post-luminal migration of T cells occurred in a PNAd-dependent manner. Remarkably, we found hot spots for the trans-EC and trans-FRC migration of T and B cells. Interestingly, T and B cells preferentially shared trans-FRC migration hot spots but not trans-EC migration hot spots. Furthermore, the trans-FRC T cell migration was confined to fewer sites than trans-EC T cell migration, and trans-FRC migration of T and B cells preferentially occurred at FRCs covered by CD11c+ dendritic cells in HEVs. These results suggest that HEV ECs and FRCs with perivascular DCs delicately regulate T and B cell entry into lymph nodes.

immunology↗