Biology subjects

Kim, G.

Publications and source records attributed to Kim, G..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Comparative analysis of varicella-zoster virus and herpes simplex virus 1 interaction with epidermal terminal differentiation in primary human keratinocytes models of differentiation

Varicella-zoster virus (VZV) is the etiological agent of chickenpox and herpes zoster, while herpes simplex virus 1 (HSV-1) causes oral and genital herpes. Both infections manifest with skin blisters from which the viruses are transmitted to new hosts either via aerosol (VZV) or skin microabrasions (HSV-1). VZV reaches the skin through the blood route, and in the skin epidermis it first infects undifferentiated keratinocytes of the basal layer. Conflicting evidence exists for HSV-1, making it unclear whether HSV-1 infects undifferentiated or differentiated keratinocytes. Here, we developed in vitro models of primary human epidermal keratinocytes differentiation to recapitulate infection of distinct layers of the epidermis by VZV and HSV-1. Our data show that replication of both viruses is restricted, VZV more than HSV-1, if initial infection occurs in differentiated keratinocytes, but not if initial infection occurs in basal undifferentiated keratinocytes. Like VZV, HSV-1 downregulates expression of proteins associated with keratinocyte differentiation, such as the suprabasal keratin K10. However, whereas in VZV downregulation of K10 occurs soon after VZV infection and appears to be independent from viral replication, HSV-1-mediated K10 downregulation requires full viral replication. These observations provide insights into the potential for VZV and HSV-1 interactions with epidermal differentiation to yield strategies for developing host- and pathogen-directed antiviral agents.

microbiology↗

bioRxiv2026

Shared and organ-specific gene expression programs of fibrotic diseases

Fibrotic scarring is a common response to tissue injury. Repeated or severe insults can cause fibrosis, leading to excessive extracellular matrix deposition and a substantial clinical risk of organ dysfunction. Despite its high prevalence, few therapeutic options exist, and fibrotic diseases collectively represent a major global health burden. Fibrotic diseases affect virtually all organs, yet they have been explored mainly in isolation for each organ. As a result, proposed shared fibrotic mechanisms are often based on indirect comparisons between independent datasets rather than on a unified, systematic, cross-organ meta-analysis. To overcome this gap, we conducted a large-scale meta-analysis of single-cell transcriptomic data from healthy and fibrotic human tissues to identify both shared and organ-specific transcriptomic profiles. We constructed a single-cell fibrosis atlas of over five million cells from 20 studies, covering more than 25 disease etiologies affecting the heart, liver, kidney, and lung. Through systematic comparison of these datasets, we identified organ-specific as well as cross-organ fibrosis-associated gene expression profiles in major cell types and defined disease fibroblast subpopulations with excessive extracellular matrix production. These analyses revealed a conserved fibrotic response shared across tissues. Our analysis spans global comparisons of fibrosis-associated changes in cellular composition and predictive disease signatures to detailed examinations of individual genes, transcription factors, and intercellular communication patterns observed in fibrotic diseases across organs. We provide our cross-organ integration as a user-friendly open resource for investigating fibrotic diseases across organs. This resource will enable an accelerated discovery of disease mechanisms and faster development of broadly effective antifibrotic strategies in the future. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/709232v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@37e26borg.highwire.dtl.DTLVardef@f1ef53org.highwire.dtl.DTLVardef@1974d4corg.highwire.dtl.DTLVardef@53f5ea_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

genomics↗

bioRxiv2026

Newly unveiled meiosis elucidates the unreduced gamete frequency and its impact on evolution of the Lemna minor complex

Fusion of gametes possessing meiotically reduced (haploid) chromosome complements is the main pathway of propagation among eukaryotes. However, duckweeds, the smallest angiosperms, propagate mainly vegetatively, and meiosis has not yet been documented in detail for this plant family. The more surprising was the recent evidence of rather frequent interspecific hybrids and triploid clonal accessions which became obvious by genome size measurements, genomic in situ hybridization (GISH) and combined plastid and nuclear DNA markers. These observations indicated sexual propagation involving reduced as well as unreduced male and female gametes in Lemna minor and L. turionifera leading to allodiploid and allotriploid hybrids (MT, MMT, MTT) and autotriploid L. minor (MMM) accessions. Here, we i) documented the meiotic stages of Lemna species for the first time; ii) provided evidence of unreduced male gametes through fluorescent in situ hybridization (FISH) with single locus probes; iii) determined their abundance in different individuals and iv) hypothesized about the reasons of unreduced male gamete formation. These findings open new insights into the modes of sexual reproduction and evolution of duckweeds which may be useful for future breeding efforts in this emerging crop.

plant biology↗

bioRxiv2026

YAP activation reverses aging-related visual dysfunction caused by impaired cell-matrix adhesion

Cellular senescence of retinal pigment epithelium (RPE) cells drives age-related visual decline, particularly in the pathology of age-related macular degeneration (AMD). While genome-wide association studies (GWAS) have identified genetic risk factors underlying AMD, the molecular mechanisms governing RPE senescence remain unclear. Here, single-cell RNA sequencing of young and old mouse RPE revealed dysregulated cell-matrix adhesion as a key feature of senescence, consistent with transcriptional changes in AMD patients. Hydrogel-based experiments confirmed that impaired integrin-mediated adhesion induces RPE senescence. Yes-associated protein 1 (YAP), a crucial mechanotransducer, mediated the protective effects of cell-matrix adhesion, and its activation alone reversed aging phenotypes in senescent RPE cells. Notably, treatment with TRULI, a small-molecule YAP activator, significantly improved visual function in AMD and naturally aged mice. These findings highlight the integrin-YAP mechanotransduction pathway as a fundamental regulator of RPE senescence and a potential therapeutic target for AMD.

physiology↗

bioRxiv2025

Intrinsic and non-cell autonomous roles for a neurodevelopmental syndrome-linked transcription factor

Transcription factors (TFs) are essential for neuronal identity, yet their potential non-cell-autonomous functions remain largely unexplored. Here, we uncover both cell- and non-cell-autonomous roles for the conserved terminal selector UNC-3 in C. elegans motor neurons (MNs). UNC-3 is an ortholog of human EBF3, mutations in which cause a severe neurodevelopmental syndrome. Single-cell RNA sequencing of cholinergic MNs, which express unc-3, and downstream GABA MNs, which do not, revealed that unc-3 loss disrupts neuronal identity in distinct ways across MN classes. Four cholinergic MN classes lose their molecular identity entirely, whereas the AS class retains it partially, illuminating terminal selector-driven neuronal diversification processes. Integrated transcriptomic and genomic analyses uncovered a dual cell-autonomous role for UNC-3 as both a direct activator and repressor of neuron-type- specific genes in cholinergic MNs, including repression of alternate neurotransmitter programs. Unexpectedly, unc-3 loss also caused widespread transcriptional, morphological, and connectivity defects in downstream GABA MNs. Mechanistically, these non-cell-autonomous effects are mediated by cholinergic neurotransmission and include activation of the pro-regenerative bZIP TF CEBP-1 (C/EBP) and dysregulation of UNC-6/Netrin signaling. These findings redefine terminal selectors as both intrinsic and extrinsic regulators of neuronal identity and circuit assembly, offering a mechanistic framework for understanding EBF3 syndrome pathogenesis.

developmental biology↗

bioRxiv2025

LoL-align: sensitive and fast probabilistic protein structure alignment

The ubiquitous availability of protein structures permits replacing sequence alignment with more accurate and sensitive structure alignment algorithms. LoL-align maximizes a local log-odds score for proteins to be homologous, given their intra-protein C - C distances. LoL-align is markedly more sensitive in detecting remote homologs than TMalign and DALI on single- and multi-domain benchmarks and achieves better alignment quality at 5-20x their speed. LoL-align is fully integrated into Foldseek.

bioinformatics↗

bioRxiv2025

Microfluidic sieve-detector for rapid capture and detection of single molecules

The advent of ultrasensitive assays enabled many new research and clinical applications, but the time-to-result is hours and has not significantly improved over time, limiting their potential. We introduce the microfluidic sieve and detector (MSD) that can sieve 200 microlitres in just one minute, and quantify captured analytes in four minutes, down to zeptomolar (10-19M) concentration. The MSD comprises half a million 8-m-diameter pores that bind analytes upon Brownian motion-induced wall collision. Digital sandwich assays are completed by sequentially flowing the sample, reagents, partitioning the pores, and digitally revealing single trapped analytes by enzymatic amplification. The MSD tests are specific and reproducible, exhibit a large dynamic range, and are easy-to-use, affordable, tuneable and versatile, enabling measurement of different proteins including influenza A nucleoprotein in clinical samples, and even nucleic acids while being both faster and more sensitive than PCR. As such, the MSD could open a new chapter for analysis and diagnostics.

bioengineering↗

bioRxiv2025

M1 Macrophage-Derived Small Extracellular Vesicles as Synergistic Nanotherapeutics: Harnessing Intrinsic Anticancer Activity and Drug Delivery Capacity

Small extracellular vesicles (sEVs) have emerged as next-generation multifunctional nanotherapeutics due to their parental-cell traits and role in intercellular communication. Among them, immune cell-derived sEVs are uniquely positioned to couple innate immunomodulatory activities with therapeutic payload delivery, making them highly attractive for cancer therapy. In particular, M1 macrophage-derived sEVs (M1-sEVs) preserve the tumor-suppressive functions of their parent cells, including tumor microenvironment (TME) reprogramming, immune activation, and inhibition of cancer progression. However, the mechanisms by which these activities are coordinated within the TME, and whether they act independently or synergistically, remain poorly understood. Clarifying these mechanisms is crucial for harnessing their intrinsic bioactivity in combination with their natural capacity as drug delivery nanocarriers to optimize therapeutic efficacy. Here, we demonstrate that M1-sEVs exhibit intrinsic stability and circulation longevity via do not eat me ligands, as well as tumor-homing ability revealed by proteomic profiling, enabling efficient uptake and deep infiltration in breast cancer models. Functionally, M1-sEVs deliver antiproliferative microRNAs that suppress tumor metabolism, growth, and progression by inhibiting self-renewal, adhesion, migration, motility, and invasion. Importantly, by integrating this endogenous bioactivity with exogenous doxorubicin loading, we achieved synergistic efficacy: a 3-fold reduction in IC50 in vitro (0.46 M vs. 1.45 M for free drug) and 70.18% tumor growth inhibition in vivo. These findings highlight M1-sEVs as dual-action nanotherapeutics that combine innate immune-regulatory and tumor-inhibitory functions with efficient drug delivery, advancing their development as powerful platforms for cancer therapy.

bioengineering↗

bioRxiv2025

YAP/TEAD4-reagulated placental alkaline phosphatases ALPP and ALPPL2 are immunosuppressive ectonucleotidases modulated by MAPK inhibitors

Placental alkaline phosphatases ALPP and ALPPL2 (ALPP/L2) are promising clinical targets for therapies such as antibody-drug conjugates (ADCs). However, their regulation and biological functions remain unclear. Here, we identify the YAP/TEAD4 signaling axis as the primary regulator of ALPP/L2 expression in tumor cells. Importantly, we demonstrate that inhibitors targeting KRAS, MEK, and ERK upregulate ALPP/L2 expression in vitro and in vivo, thereby enhancing the efficacy of antibody-drug conjugates (ADCs) when used in combination. Moreover, our work reveals a novel immunomodulatory function of ALPP/L2 as cell surface ectonucleotidases that hydrolyze extracellular ATP, ADP, and AMP to adenosine, promoting regulatory T cell infiltration into the tumor microenvironment. Together, these findings reveal a biological function of ALPP/L2 and identify druggable regulators to enhance ALPP/L2-targeted therapies. SIGNIFICANCEThis study uncovers the YAP/TEAD pathway as a positive regulator of the clinically relevant tumor-associated antigens ALPP and ALPPL2. Kras, MEK, or ERK inhibitors enhance ALPP/L2 expression in tumor cells, thereby increasing the efficacy of ALPP/L2-targeted antibody-drug conjugates. These findings offer a promising combination strategy to overcome resistance to ALPP/L2-based therapies caused by low target expression.

cancer biology↗

bioRxiv2025

Nanochirality-programmed Type-I photosensitizer enables deep-tumor photodynamic therapy by reducing extracellular-matrix adhesion

Tumor hypoxia and poor penetration of therapeutics across tumor-microenvironment barriers remain major obstacles to effective cancer therapy, including photodynamic therapy (PDT). Here we introduce a nanochirality-programmed assembly (L-Chi-GAIN) in which nanochirality drives site-selective assembly that activates oxygen-independent Type-I reactive oxygen species (ROS) generation and reduces hyaluronan-mediated matrix adhesion, thereby permitting deep intratumoral therapy. Glycosylation imparts structural chirality to graphene quantum dots (GQDs), directing site-selective assembly of indocyanine green (ICG) that turns on photoinduced electron transfer (PET), producing a 64-fold increase in ROS relative to free ICG. Nanochirality also modulates assembly-extracellular matrix (ECM) interactions. L-GQDs show a less favorable hyaluronan binding free energy ({Delta}Gbind), thus accelerating interstitial transport and resulting in [~]21-fold deeper tumor penetration by L-Chi-GAIN than conventional nanocarriers. Under near-infrared irradiation, L-Chi-GAIN elicits strong oxidative stress and triggers Gasdermin-D (GSDMD)-dependent pyroptosis, leading to significant suppression of tumor growth. This work offers a nanochirality-guided design strategy for PDT in deep tumors by coupling site-selective assembly with stereoselective navigation of the ECM.

bioengineering↗

bioRxiv2025

A Covalent PFKL Activator Suppresses Tumor Growth

Glycolysis fuels vital cellular functions and its dysregulation is implicated in cancer, neurodegeneration, antibiotic resistance and diabetes. The glycolytic dependency of cancer, known as the Warburg effect, presents a key vulnerability for developing targeted anticancer agents but remains challenging due to metabolic heterogeneity and resistance. Here, we developed a first-in-class covalent phosphofructokinase-1 liver type (PFKL) activator that induces metabolic imbalance coupled to delivery of a cytotoxic payload to cancer cells in vitro and in vivo. The electrophile-drug conjugate (EDC) site-specifically and proteome-wide selectively modifies K677 in the allosteric effector site to stabilize the R-state tetramer of PFKL and destabilize cell metabolism. We introduce EDCs as a new delivery mechanism analogous to antibody-drug conjugates but differentiated by selective covalent targeting of intracellular proteins.

biochemistry↗

bioRxiv2025

Sorghum embryos undergoing B chromosome elimination express B-variants of mitotic-related genes

BackgroundSelective DNA elimination occurs across diverse species and plays a crucial role in evolution and development. This process encompasses small deletions, complete removal of chromosomes, or even the elimination of entire parental genomes. Despite its importance, the molecular mechanisms governing selective DNA elimination remain poorly understood. Our study focused on the tissue-specific elimination of Sorghum purpureosericeum B chromosome(s) during embryo development. ResultsIn situ B chromosome visualisation, complemented by transcriptomic profiling and gene-enrichment analysis, allowed us to identify 28 candidate genes poten-tially linked to chromosome elimination. We show that elimination is a developmentally programmed process, peaking during mid-embryogenesis and nearly completed at later stages, leaving B chromosomes only in restricted meristematic regions. Genome sequencing revealed that the sorghum B chromosome is of multi-A chromosomal origin, has reduced gene density, is enriched in repetitive sequences, and carries a novel centromeric repeat (SpuCL166). Transcriptome analyses identified B-specific variants of kinetochore, cohesion, and checkpoint genes that are expressed during active elimination, while structural modeling of CENH3 and CENP-C indicated functional divergence at the kinetochore interface. ConclusionHere, we provide the first comprehensive genomic and transcriptomic characterization of B chromosome and its elimination in Sorghum purpureosericeum. Our findings suggest that B chromosomes express modified mitotic machinery to control their own fate. By establishing a framework of candidate genes, this study opens new avenues for dissecting the molecular mechanisms of chromosome elimination and provides a critical foundation for understanding how genomes evolve to regulate and tolerate supernumerary chromosomal elements.

plant biology↗

bioRxiv2025

Validation of Dynamic Bayesian Optimization for a Non-Stationary Human-in-the-Loop Optimization Problem

Human-in-the-Loop Optimization (HILO) has demonstrated efficacy in achieving a plethora of assistive or augmentative effects. However, conventional optimizers such as Bayesian optimization (BO) do not account for the non-stationary aspects of the human-robot system, and may thus be limited in the domains of robot-assisted training or rehabilitation. In this study, we implemented HILO using dynamic Bayesian optimization (DBO) to define the optimal value of a single control parameter to target a desired effect in propulsion mechanics, specifically in the maximum hip extension (HE) angle during stance. Sixteen healthy participants received unilateral hip torque pulses via a hip exoskeleton for about 15 minutes while walking on a treadmill. Exoskeleton torques were determined via HILO using DBO or BO. Unknown to the optimizers, treadmill speed was gradually increased to amplify the non-stationary behavior of the system. Experimental results revealed that DBO outperformed BO in the later stages of training, leading to improved cost and to final values of torques closer to the true value. The primary difference between optimizers arose from their ability to model the history-dependent relationship between applied torque and output. BO associated later deviations between expected and measured output to process noise, while DBO developed a more accurate predictive model of the input-output relationship that gave proper weighing to past datapoints for making predictions.

bioengineering↗

bioRxiv2025

β-sheet stabilization of the island domain underlies ligand-induced LRR-RP activation of plant immune signaling

Leucine-rich repeat (LRR) receptor kinases (RKs) and receptor proteins (RPs) are important classes of plant pattern recognition receptors (PRRs) activating pattern-triggered immunity. While both classical and AI-based structural approaches have recently provided crucial insights into ligand-LRR-RK binding mechanisms, our understanding of ligand perception by LRR-RPs remains limited. In contrast to LRR-RKs, many LRR-RPs typically embed one or more loopout regions in their extracellular domains that are crucial for functionality. Here, we employed an AI-based approach to reveal a novel ligand-binding mechanism shared by the Arabidopsis LRR-RPs RLP23 and RLP42 - the PRRs for the short peptide ligands nlp20 and pg13, derived from NECROSIS- AND ETHYLENE-INDUCING PEPTIDE 1-like proteins (NLPs) and fungal endopolygalacturonases (PGs), respectively. This mechanism relies on a {beta}-strand interaction with the N-terminal part of the island domain (ID) loopout, which adopts an antiparallel {beta}-sheet conformation. Additionally, we investigated the larger and more complex binding interface of RLP32 - the PRR for proteobacterial TRANSLATION INITIATION FACTOR 1 (IF1), a folded protein ligand that requires its tertiary structure for recognition. Finally, we describe a mechanistic role of the ID for co-receptor recruitment conserved across LRR-RPs. Together, our results shed light on the ligand-binding mechanisms and receptor complex formation of this important class of PRRs. This opens avenues for a molecular understanding of the plant-pathogen co-evolution, as well as the engineering of plant immune receptors for crop disease resistance.

plant biology↗

bioRxiv2025

Automated High-Content, High-Throughput Spatial Analysis Pipeline for Drug Screening in 3D Tumor Spheroid Inverted Colloidal Crystal Arrays

High-content, high-throughput (HCHT) screening platforms are essential for drug discovery, yet conventional 2D assays lack physiological relevance, and current 3D spheroid systems often face challenges to scalability, uniformity, and the analytical efficiency required for statistically robust screening. Here, we present a fully integrated 3D HCHT platform that synergizes tumor spheroid arrays generated from a bioinert inverted colloidal crystal (iCC) hydrogel frame-work with an automated, high-speed image analysis pipeline for rapid and spatially resolved therapeutic profiling. The iCC framework enables spontaneous self-assembly of highly-ordered tumor spheroid array at high spheroid density ([~]79.8 spheroids{middle dot}mm-2) with tight size uniformity (<10% standard deviation), supporting reproducible and high-content imaging ([~]40 spheroids{middle dot}image-1). The automated image-processing algorithm achieves robust region-of-interest segmentation, fluorescence-weighted centroiding, and multi-parametric spatial analysis in <5 seconds per image--markedly faster than conventional well-plate (5 min per 96 throughput) or single-spheroid analysis workflows methods ([~]1 sec per spheroid). Using this platform, we capture dose-dependent diffusion of doxorubicin, tumor penetration profile of small extracellular vesicles, and cell-type-specific infiltration behaviors of monocytes versus macrophages. Comparative viability profiling across chemotherapeutics further reveals distinct spatial toxicity signatures, highlighting the importance of spatial context in drug response assessment. Collectively, this platform enables rapid, reproducible, and spatially informative screening in 3D, offering a powerful tool for drug discovery, tumor modeling, and immunotherapeutic development.

cancer biology↗

bioRxiv2025

FERONIA defines intact tissue boundaries through cuticle development

Plant cuticle is the first hydrophobic barrier between the epidermis and the environment. Upon wounding, damaged tissues undergo healing processes that involve cuticle or callus formation at the wound site. However, signaling pathways that initiate cuticle development and callus formation in the wound-proximal region are still poorly understood. Here, we reveal that the FERONIA receptor-like kinase facilitates cuticle development in the epidermis and FER-mediated cuticle formation limits the propagation of wound-induced reactive oxygen species (ROS), which trigger callus formation. Cuticle defects stimulate NADPH oxidase-dependent ROS production, which leads to unrestricted callus formation. However, the cuticle formed in mesophyll cells in the vicinity of the wound suppresses ROS propagation, thereby preventing unorganized callus formation beyond the wound-proximal site and activating programmed cell death adjacent to the wound. These findings provide valuable insights into cuticle development in aerial tissues and its defensive function for preserving the integrity of undamaged regions.

plant biology↗

bioRxiv2025

Spurring and Siloing: Identity Navigation in Scientific Writing Among Asian Early-Career Researchers

Scientific writing and publication are critical sites where students must navigate between personal identities and presumed scientific objectivity. For non-white student researchers, particularly those stereotyped as "model minorities," this process involves complex negotiations. This qualitative study examines how Asian and Asian American students navigate ethnic and cultural identities within scientific writing processes. Using an integrated theoretical framework combining cultural community wealth, narrative identity, and border crossing, we analyzed how participants deployed cultural resources while navigating institutional expectations. Drawing on interviews with 23 student participants who engaged with the [Blinded Journal], we identified two primary approaches: "spurring," wherein ethnic and cultural backgrounds catalyze research questions, and "siloing," wherein these identities are deliberately compartmentalized during writing. Findings reveal that while participants drew upon familial capital to inform research interests, most practiced disciplinary compartmentalization and adhered to perceived scientific norms. This tension demonstrates how students negotiate cultural scripts while developing professional identities. Our findings suggest that science educators could help students recognize their cultural backgrounds as valuable epistemic resources rather than sources of bias, explicitly address the myth of value-neutral science, and provide models of how scientists integrate personal and cultural perspectives into rigorous scientific work.

scientific communication and education↗

bioRxiv2025

Locomotion-induced neural activity independent of auditory feedback in the mouse inferior colliculus

Accumulating evidence indicates that the auditory pathway integrates movement-related signals with auditory input, yet the precise sources and mechanisms of this integration across various processing levels are incompletely understood. The inferior colliculus (IC), a major midbrain hub in the auditory pathway, shows widespread modulation of neural activity during locomotion, indicating that auditory neurons at this level are sensitive to ongoing movement. However, in hearing animals, it has been challenging to dissociate auditory feedback from other motor-related signals. In this study, to isolate non-auditory contributions, we recorded IC neural activity during locomotion in deafened mice, thereby eliminating all auditory feedback through both air and bone conduction. Even in the absence of auditory input, IC neurons exhibited robust, bidirectional modulation during locomotion. Timing analysis using electromyography revealed both predictive and feedback components relative to locomotion onset. Furthermore, the timing and direction of modulation varied considerably across different locomotion bouts, suggesting convergence of multiple non-auditory inputs. These findings demonstrate that non-auditory, movement-related signals significantly shape auditory midbrain activity through both predictive and feedback mechanisms.

neuroscience↗