Biology subjects

Jeon, J.

Publications and source records attributed to Jeon, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Re-evaluation of the report of Culex quinquefasciatus in the Republic of Korea: Molecular evidence of cryptic hybridisation within the Culex pipiens complex

The Culex pipiens complex comprises globally distributed mosquito species that serve as vectors for various arboviruses and filariasis. Female mosquitoes within the Cx. pipiens complex are morphologically very similar, making species identification based on morphologically characteristics challenging. To date, Cx. pallens and Cx. pipiens f. molestus have been reported to inhabit the Republic of Korea (ROK). Conversely, Cx. quinquefasciatus, predominantly distributed in tropical regions, has not been documented in the country since a single record in the 1950s. Recently, however, Cx. quinquefasciatus was reported from the Jeju region of the ROK based on molecular identification. This study aimed to re-evaluate the occurrence of Cx. quinquefasciatus in the ROK by conducting molecular identification using the ace-2 and CQ11 markers on Cx. pipiens complex specimens collected nationwide, including from Jeju, where Cx. quinquefasciatus had previously been reported. Our analysis identified only Cx. quinquefasciatus-Cx. pallens hybrid individuals among the Cx. pipiens complex specimens from the Jeju region, highlighting the need to re-evaluate the analytical methods used in previous studies that reported the presence of pure Cx. quinquefasciatus. These findings provide essential evidence for future surveillance of the distribution, introduction, and establishment of Cx. quinquefasciatus and underscore the need for continuous monitoring.

evolutionary biology↗

bioRxiv2026

A Conserved Flexible N-Terminal Domain Tunes the Calcium Sensitivity of Sorcin by Stabilizing Its Active Conformation

Sorcin is a penta-EF-hand Ca2+-binding protein that acts as a Ca2+ sensor and regulator of Ca2+ homeostasis. Although the structure and Ca2+-dependent activation of Sorcin is well characterized, the function of its flexible N-terminal domain (NTD) remains unclear. We combined sequence analysis, Ca2+-induced aggregation assays, multidimensional NMR spectroscopy, and long-timescale molecular dynamics (MD) simulations to define the NTDs role in Sorcin activation. Sequence comparisons showed that the NTD is conserved across vertebrates despite its intrinsic disorder, indicating functional importance. NTD deletion markedly reduced Ca2+ responsiveness. Relative to full-length Sorcin, the construct with NTD truncation required more than twofold higher Ca2+ concentrations and over tenfold higher protein concentrations to initiate aggregation, while aggregation kinetics slowed by nearly three orders of magnitude. Temperature-dependent measurements yielded an apparent activation energy of 36.7 kJ{middle dot}mol-1, consistent with aggregation driven by Ca2+-induced conformational activation rather than denaturation. NMR chemical shift perturbations localized the effects of NTD removal to the EF-hand Ca2+-binding loops and adjacent D-helix. Apo-state MD simulations revealed transient intra- and intermolecular NTD-SCBD contacts that explain some perturbations and support direct and allosteric regulation. Ca2+-bound simulations further showed that SCBD departs more readily from the crystallographic active conformation than full-length Sorcin, indicating that the NTD stabilizes the active state through dynamic contacts. Together, these findings establish the NTD as a critical regulator that enhances Ca2+ responsiveness by shifting Sorcins conformational equilibrium toward the active state and suggest that flexible N-terminal extensions regulate signaling within the penta-EF-hand protein family.

biophysics↗

bioRxiv2026

MagNet: Computational Methods for Constructing High-Confidence Protein-Protein Interaction Networks in Magnaporthe oryzae

Magnaporthe oryzae, the rice blast fungus, plays a role as a model organism for molecular plant-microbe interaction research. Studies on the pathogenic mechanism of this fungus revealed many genes involved in signaling pathways. As multi-omics data are being available, genomic-level researches have been conducted to uncover the underlying biological processes during the pathogenesis of M. oryzae. Identifying the genome-wide protein-protein interaction (PPI) network is one of the omics-level approaches, which helps to understand signaling and regulatory pathways. However, existing biological network resources of M. oryzae are not sufficient to decipher pathogenesis mechanisms due to the abundance of false positives/negatives. In this study, a reliable PPI network database of M. oryzae, MagNet, was constructed with three methods, including homology-based Interolog search, co-expression network construction, and domain-domain interaction (DDI)-based prediction. With three approaches altogether, the pan-network with 5,600,976 interactions was generated, including 217,531 highly confident interactions supported by all three methods. Experimental data on M. oryzae PPIs supported that our PPI network can predict PPIs with higher accuracy compared to the previously constructed databases. MagNet would provide integrated biological network data, which can help to understand the molecular mechanisms of the rice blast fungus. The PPI data can be accessed via https:/magnet.scnu.ac.kr.

genomics↗

bioRxiv2026

Janus kinase 2 regulates Nurr1 protein stability in dopaminergic neurons of the aging midbrain

The nuclear receptor Nurr1 (NR4A2) is an essential transcription factor that governs the differentiation, maturation, and long-term maintenance of midbrain dopaminergic (mDA) neurons in the substantia nigra. Reduced Nurr1 expression has been closely linked to age-related dopaminergic neuronal loss and the pathogenesis of Parkinsons disease. However, the molecular mechanisms regulating Nurr1 expression and protein stability in the aging midbrain remain poorly understood. Here, we identify Janus kinase 2 (JAK2) as a previously unrecognized regulator of Nurr1 in mDA neurons. In the substantia nigra of aged mice (12-and 18-month-old), JAK2 was robustly expressed in Nurr1-positive mDA neurons, whereas its expression was minimal in young adult mice. In SK-N-BE(2)C neuroblastoma cells, overexpression of JAK2 modestly enhanced Nurr1 transcriptional activity, while the constitutively active mutant JAK2V617F markedly increased it. Notably, this effect was not blocked by pharmacological inhibition of STAT, PI3K, or Akt signaling pathways, indicating that JAK2 regulates Nurr1 independently of canonical JAK/STAT or PI3K/Akt signaling. Mechanistically, JAK2 did not promote tyrosine phosphorylation of Nurr1 but instead physically interacted with Nurr1, leading to enhanced nuclear stability of the Nurr1 protein. Consistent with this mechanism, expression of JAK2V617F increased Nurr1 protein levels without altering its mRNA expression. Functionally, co-expression of JAK2V617F and Nurr1 attenuated oxidative stress-induced cytotoxicity and reduced reactive oxygen species accumulation. Together, these findings reveal a phosphorylation-independent mechanism by which JAK2 stabilizes Nurr1 protein and enhances its transcriptional activity. Our results further suggest that age-associated induction of JAK2 in dopaminergic neurons may promote neuronal resilience by maintaining Nurr1 protein stability during aging.

neuroscience↗

bioRxiv2026

A plant virus, TYLCV, up-regulates an endocrine oxylipin signal in its insect vector, Bemisia tabaci, via the viral C2 virulence factor for viral transmission

To survive and efficiently transit between plant and insect hosts, circulative plant viruses have evolved sophisticated strategies to exploit insect vector factors. Tomato yellow leaf curl virus (TYLCV) is transmitted by Bemisia tabaci through a circulative and replicative pathway. In insects, C20 oxylipin (eicosanoid) and C18 oxylipin (EpOME) antagonistically regulate antiviral responses. Upon TYLCV infection, the intestinal apoptosis of B. tabaci facilitated the viral multiplication. The apoptosis was suppressed by eicosanoid but induced by EpOME. EpOME treatment also upregulated other proviral factors, including defensin, PGRP, and cathepsins, while eicosanoid signaling exerted opposite effects. TYLCV infection suppressed eicosanoid biosynthetic enzymes but induced a cytochrome P450 gene involved in EpOME biosynthesis, consistent with elevated EpOME levels in the viruliferous B. tabaci detected by LC-MS/MS. Individual RNA interference treatments specific to each of the TYLCV genes in the viruliferous insects revealed that only silencing of the viral C2 gene abolished EpOME-mediated proviral effects. These findings uncover a lipid-mediated mechanism by which TYLCV enhances vector competence to promote transmission. IMPORTANCEVarious plant viruses depend on insect vectors for their horizontal transfer. Some of them exhibit a circulative and propagative transmission by multiplying the viral titers within the insects using the host machinery. Here is a fascinating manipulation of the host immunity by a plant virus, tomato yellow leaf curl virus (TYLCV), which uses the insect endocrine signals associated with immunity of its vector, Bemisia tabaci. Two types of oxylipins, eicosanoid and EpOME, antagonistically act to insect immunity, in which eicosanoid induces immune responses while EpOME, as an insect immune resolvin, suppresses them. TYLCV uses its C2 gene component as a virulent factor to induce the EpOME biosynthesis of B. tabaci. The elevated EpOME levels in the vector insect led to proviral responses by inducing intestinal apoptosis and selectively suppressing the immune-associated genes. These findings demonstrate the viral manipulation of the host endocrine signal for inducing proviral responses.

plant biology↗

bioRxiv2026

Spatial transcriptomic analysis of progressing oral epithelial dysplasia reveals unique differentially expressed genes and microenvironmental changes.

Oral squamous cell carcinoma (OSCC) often arises from oral epithelial dysplasia (OED); however, the gene expression changes during OED progression and its microenvironment are not fully understood. This study used spatial transcriptomics to identify differentially expressed genes and microenvironmental alterations associated with OEDs malignant transformation of OED. A ten-year retrospective analysis of paired OSCC and prior OED samples was conducted at the University of Toronto Oral Pathology Laboratory. A total of 24 paired progressing OED cases and 23 matched non-progressing OED cases were examined using spatial transcriptomics in PanCK+ (dysplastic epithelium or OSCC) and PanCK- (stroma) regions. The analysis included differential gene expression, pathway analysis and spatial deconvolution. Three genes (STOM, KIF26A, and CDKN2A) showed increased expression in the epithelial component of progressing OED compared with non-progressing OED, whereas 41 genes were differentially expressed in OSCC versus the precursor samples. Ubiquitination-related pathways were enriched during OED progression. Functional validation identified TNFRSF12A (Fn14) as a potential regulator of OED progression to OSCC. The OSCC microenvironment displayed increased numbers of fibroblasts, neutrophils, monocytes, and mast cells compared with that of the precursor samples. Our findings suggest that spatial profiling of OED can help identify unique gene signatures and microenvironmental changes that occur before the malignant transformation.

cancer biology↗

bioRxiv2026

Tumor-infiltrating natural killer cell profiling for therapeutic stratification in patients with resectable non-small cell lung cancer

ObjectiveNeoadjuvant chemoimmunotherapy has improved outcomes in resectable non-small cell lung cancer (NSCLC), yet its real-world implementation is often challenged by surgical delays, immune-mediated fibrosis, and postoperative complications. Smokers with NSCLC, despite a high risk for surgical morbidity, show enhanced responses to neoadjuvant chemoimmunotherapy. This study aimed to identify smoking-associated immune cell determinants that could guide treatment strategies. MethodsSingle-cell RNA sequencing (scRNAseq) was performed on 61 lung tissues from non-smokers and smokers to identify smoking-related immune compositions. The scRNAseq data from 19 invasive lung adenocarcinomas were used to validate their presence in the tumor-immune microenvironment. Bulk RNA sequencing data from 102 resected NSCLC and 24 NSCLC patients treated with neoadjuvant chemoimmunotherapy followed by surgery were used for in silico cellular deconvolution and outcome analyses. ResultsAmong 135 lung cellular phenotypes, two natural killer (NK) cell subsets were strongly associated with smoking and chronic obstructive pulmonary disease (COPD) severity. "Stress-responsive" NK (NKSR) cells exhibited immature features and cytokine-responsive features, and "Adaptive and immunoregulatory NK" (NKAIR) cells showed mature features and elevated multiple immune checkpoint expression. High intratumoral NKSR cells correlated with improved survival after surgery, particularly in current smokers. Conversely, tumors with low NKSR and high NKAIR cells responded more favorably to neoadjuvant chemoimmunotherapy. ConclusionsIntratumoral NK cell phenotyping may aid in therapeutic stratification in patients with NSCLC. NKSR cell preservation predicts benefit from upfront surgery, while NKAIR cell enrichment indicates improved response to neoadjuvant chemoimmunotherapy. These NK cell profiles may help optimize treatment by balancing therapeutic benefit and risk. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/696292v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@168bc03org.highwire.dtl.DTLVardef@10fa947org.highwire.dtl.DTLVardef@132a92dorg.highwire.dtl.DTLVardef@100e4a4_HPS_FORMAT_FIGEXP M_FIG C_FIG Central Picture O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/696292v1_ufig2.gif" ALT="Figure 2"> View larger version (21K): org.highwire.dtl.DTLVardef@1a2d3b4org.highwire.dtl.DTLVardef@f8f84borg.highwire.dtl.DTLVardef@17510bcorg.highwire.dtl.DTLVardef@9da763_HPS_FORMAT_FIGEXP M_FIG C_FIG NK cell profiling for treatment stratification in resectable NSCLC Central MessageTumor-infiltrating NK cell profiling identifies distinct immune phenotypes that can inform personalized treatment strategies in resectable NSCLC. Perspective statementAbundance of intratumoral stress-responsive NK cells predicts favorable outcomes after upfront surgery, whereas enrichment of adaptive and immunoregulatory NK cells suggests greater benefit from neoadjuvant chemoimmunotherapy. These findings support incorporating NK-cell profiling into preoperative decision-making to optimize therapy selection and balance risks in the high-risk surgical population.

immunology↗

bioRxiv2025

Telomere-to-Telomere Accurate and Gapless Korean Standard Reference Genome

We present KOREF1-G-TTAGGA, the first Telomere-to-Telomere Accurate and Gapless Genome Assembly, standing as the Korean standard reference genome. The paternal and maternal haplotypes spanned 2.91 and 3.03 Gb. Genome-wide, at least 99.15% of assembled sequences were reliably haplotype-resolved, and over 95% remained accurate even in the most error-prone loci, including centromeric satellite arrays and segmental duplications. Rare-k-mer copy-number concordance within satellite arrays held up 98.9% and 98.8% per haplotype. Bionano optical maps fully spanned all canonical rDNA arrays on the five acrocentric chromosomes. The assembly quality index (AQI) of 99.77 and 99.69 exceeded the reference-quality threshold of 90, and more than 99.99% of gene and cCRE sequence was free of structural error. Both haplotypes further showed high base-level accuracy, with consensus quality value (QV) of 81.19 and 79.03, corresponding to one error per 131 and 80 Mb. KOREF1-G-TTAGGA is among the highest-quality East Asian telomere-to-telomere assemblies. It moreover anchors a decade-spanning multi-ome reference dataset for defining individual molecular states. Together, these resources define the personal referenceome as a foundation for individual biology and precision medicine, with the assemblies, annotations, and all multi-omic data openly available at https://koreanreference.org.

genomics↗

bioRxiv2025

10,239 whole genomes with multiomic and clinical health information as the Korean population multiomic reference dataset

We present Korea10K, the largest genomic dataset of the Korean population, comprising 10,239 high-coverage whole genomes (mean depth 30x) with matched multiomic profiles and phenotype data. Korea10K achieves complete and near-complete discovery of very rare and ultra-rare alleles, respectively, at 9,000 Korean genomes. This dataset provides the high-quality population-specific imputation panel, enabling accurate inference of low-frequency variants. Admixture analyses confirm the genetic homogeneity of the Korean population, despite its diverse Y-chromosomal, mitochondrial, and HLA repertoires. This pattern reflects a long and continuous lineage history characterized by persistent internal admixture and genomic homogenization over thousands of years on the Korean peninsula. We also identified 16.8 million genomic variants that directly modify CG sites by creating or abolishing CG dinucleotides, providing the population-scale evidence of coordinated genomic-epigenomic regulatory mechanism in Koreans.

genomics↗

bioRxiv2025

Development of Recombinant Anti-TLR2 Antibodies and PLGA Nanoparticle-based Gene Therapy for the Treatment of Neuropathic Pain

Neuroinflammation is a key contributor to neuropathic pain, with microglial Toll-like receptor 2 (TLR2) playing a central role in initiating and sustaining proinflammatory responses. However, existing TLR2-targeting antibody therapies are limited by poor delivery to the central nervous system and short-lived efficacy. We developed a non-viral gene therapy strategy using biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to deliver recombinant anti-TLR2 antibody genes. High-affinity nanobody and single-chain variable fragment candidates were selected through phage display screening and shown to suppress TLR2-dependent signaling both in vitro and in vivo. In mouse models of neuropathic pain, a single intrathecal administration of PLGA NP-encapsulated antibody genes produced robust and sustained analgesia, accompanied by reduced glial activation and proinflammatory cytokine expression. These findings demonstrate a modular NP-based platform for sustained antibody expression in the central nervous system and establish its potential for the treatment of chronic pain driven by innate immune activation.

neuroscience↗

bioRxiv2025

Kinetic investigation of calcium-induced Sorcin aggregation by stopped-flow light scattering

Sorcin, a penta-EF hand calcium-binding protein, is implicated in multidrug resistance (MDR) in various cancers and has roles in neurodegenerative diseases. It regulates cellular calcium homeostasis by interacting with calcium channels, pumps, and exchangers in a calcium-dependent manner. Calcium binding induces a conformational change in Sorcin, exposing hydrophobic surfaces that mediate protein interactions and calcium flux between the cytosol and endoplasmic reticulum (ER). These exposed surfaces can also drive Sorcin aggregation in the absence of binding partners. Here, we exploited calcium-induced conformational changes and aggregation of Sorcin as a model to study its calcium sensitivity and aggregation mechanisms. Stopped-flow light scattering revealed that Sorcin aggregation is reversible, cooperative, and primarily influenced by Sorcin concentration rather than physiological calcium levels. Our findings suggest that calcium sensitivity of Sorcin is finely tuned by its expression level, highlighting its role as an intracellular calcium sensor. This work establishes Sorcin as a model system for studying protein aggregation mechanisms with implications for MDR and neurodegenerative diseases.

biophysics↗

bioRxiv2025

Microsporidia infection alters C. elegans lipid levels

Microsporidia are fungal-related obligate intracellular parasites that infect many types of animals. Microsporidia have exceptionally reduced genomes resulting in limited metabolic capabilities and are thought to be reliant on host metabolism to fuel their own growth. Here, we investigate the impact of microsporidia infection on host lipid metabolism using the nematode Caenorhabditis elegans along with its natural microsporidian pathogen Nematocida parisii. We show that infection causes an increase in the level of C. elegans lipid droplet associated lipase, ATGL-1, and a decrease in host fat levels. A mutation that decreases ATGL-1 activity and overexpression of ATGL-1 did not significantly change N. parisii infection levels. Using lipidomics we show that N. parisii infection decreases C. elegans triglyceride levels and results in increased ceramides that we speculate are synthesized by N. parisii. Mutations in host genes involved in ceramide synthesis did not significantly change the levels of N. parisii infection. Together these results show that microsporidia can cause changes to lipid metabolism of their hosts, but some individual mutations of C. elegans lipid enzymes do not alter microsporidian growth.

microbiology↗

bioRxiv2025

Enhanced mRNA delivery using ultrasound-delivered click reactive anchors

Therapeutic nucleic acid delivery has many potential applications, but it remains challenging to target extrahepatic tissues in a flexible and image-guided manner. To address this issue, we report a bioorthogonal pre-targeting strategy that uses focused ultrasound to promote the delivery of mRNA-loaded lipid nanoparticles (mRNA-LNP). We synthesized amphiphilic click reactive anchors (ACRAs) consisting of a phospholipid PEG-conjugate functionalized with transcyclooctene (TCO) or its companion reactive partner methyltetrazine (mTz), yielding ACRA-TCO and ACRA-mTz. ACRA derivatives were screened for cellular activity, yielding functionalized DOPE-PEG (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N- (polyethylene glycol)) derivatives outperforming those containing saturated lipid or branched PEG. Nanobubbles encapsulating ultrasound-responsive gas precursor delivered ACRA-TCO to targeted cells and tissues using focused ultrasound, and this pre-targeting promoted the subsequent delivery of mRNA- LNP functionalized with companion ACRA-mTz. In cell cultures and in mice, ultrasound pre-targeting enhanced the accumulation of mTz-functionalized small molecule and nanoparticle compounds by 75% and 3.6-fold, respectively, and increased gene expression using mRNA-LNP in vivo. Taken together, this report presents a modular, ultrasound-enabled strategy for enhancing nucleic acid delivery in targeted tissues.

bioengineering↗

bioRxiv2024

Mechanisms of synergistic Mediator recruitment in RNA polymerase II transcription activation revealed by single-molecule fluorescence

Transcription activators trigger transcript production by RNA Polymerase II (RNApII) via the Mediator coactivator complex. Here the dynamics of activator, Mediator, and RNApII binding at promoter DNA were analyzed using multi-wavelength single-molecule microscopy of fluorescently labeled proteins in budding yeast nuclear extract. Binding of Mediator and RNApII to the template required activator and an upstream activator sequence (UAS), but not a core promoter. While Mediator and RNApII sometimes bind as a pre-formed complex, more commonly Mediator binds first and subsequently recruits RNApII to form a preinitiation complex precursor (pre-PIC) tethered to activators on the UAS. Interestingly, Mediator occupancy has a highly non-linear response to activator concentration, and fluorescence intensity measurements show Mediator preferentially associates with templates having at least two activators bound. Statistical mechanical modeling suggests this "synergy" is not due to cooperative binding between activators, but instead occurs when multiple DNA-bound activator molecules simultaneously interact with a single Mediator.

biochemistry↗

bioRxiv2024

Preclinical Pediatric Molecular Analysis for Therapy Choice (MATCH)

Pediatric solid tumors arise from diverse tissues during development and exhibit a wide range of molecular, cellular and genetic features. This diversity, combined with the low incidence of pediatric cancer makes it increasingly difficult to personalize therapy for individual patients based on the unique features of their tumors. Therefore, well-credentialed preclinical models that capture the diversity and heterogeneity of pediatric solid tumors are essential for identifying molecular targeted therapeutics for precision medicine. Here, we report 281 orthotopic patient derived xenografts (O-PDXs) from 224 patients representing 24 different types of pediatric solid tumors. We have performed genomic characterization of the O-PDXs and compared them to their corresponding patient tumors. To demonstrate the feasibility and utility of using such a diverse collection of O-PDXs in preclinical studies, we performed a preclinical pediatric precision medicine trial based on the NCI-COG Pediatric MATCH trial enrollment criteria. We also tested molecular targeted therapy for a novel oncogenic fusion recently reported in pediatric melanoma and precision drug delivery using nano-liposomal irinotecan. Our studies demonstrate the value of large, well-credentialed preclinical models for future precision medicine in pediatric oncology using single agents, drug combinations and novel drug formulations. Translational RelevanceThis study demonstrates the value of utilizing fully characterized preclinical models of pediatric solid tumors to evaluate the response to precision medicine approaches. Our results demonstrate the importance of performing comprehensive preclinical testing using multiple orthotopic patient derived xenografts to validate and prioritize vulnerabilities identified through genomic or integrated analyses which can be translated into clinical trials. Importantly, this study identified combinations using nano-liposomal irinotecan in a precision drug delivery approach that may benefit pediatric solid tumor patients. In addition, all models and their associated data are made freely available to the scientific community through the Childhood Solid Tumor Network.

cancer biology↗

bioRxiv2024

Predicting the physiological effects of multiple drugs using electronic health record

Various computational models have been developed to understand the physiological effects of drug-drug interactions, which can contribute to more effective drug treatments. However, they mostly focus on interactions of only two drugs, and do not consider the patient information. To address this challenge, we use publicly available electronic health record (EHR), MIMIC-IV, to develop machine learning models that predict the physiological effects of two or more drugs. This study involves extensive preprocessing of laboratory measurement data, prescription data and patient data. The resulting machine learning models predict potential abnormalities across 20 selected measurement items (e.g., concentrations of metabolites and blood cells) in the form of a sentence. The models showed an average AUROC of 0.75, and age, specific active pharmaceutical ingredients, and gender appeared to be the most influential features. The model development process showcased in this study can be extended to other measurement items for a target EHR.

systems biology↗

bioRxiv2024

Molecular tension authenticates apoptotic cells being phagocytosed.

Profound cytoskeletal reorganization and plasma membrane deformation in phagocytes is indispensable for phagocytosis of massive apoptotic cells, but whether these dynamics accompany a mechanical signal modulating signaling during efferocytosis remains largely unexplored. Here, we report that tension between phosphatidylserine (PS) and PS receptors (PSR) generated at the phagocytic synapse serves as a signal to determine whether PS-exposing cells should be phagocytosed. Mechanistically, increased membrane tension of phagocytes via Rac1-dependent actin polymerization and membrane stiffness of apoptotic cells caused tension between PS and PSRs, leading to phosphoinositide 3-kinase recruitment to PSRs, which resulted in Rac1 inactivation and myosin II phosphorylation required for phagocytic cup closure. Our observations imply that tension between PS and PSRs acts as a mechanical fail-safe to prevent removal of all PS-exposing cells for the integrity of efferocytosis. One-Sentence SummaryTension between phosphatidylserine and its receptors acts as a final decision-maker determining phagocytosis of apoptotic cells.

cell biology↗

bioRxiv2023

Genome-wide exploration of metabolic-based pyrethroid resistance mechanism in Helicoverpa armigera

To elucidate the deltamethrin resistance mechanism in Helicoverpa armigera, we explored mutations at the deltamethrin target site, genomic level variations between insecticide-susceptible and -resistant strains, and differences in gene expression patterns between the strains. Known pyrethroid resistance-associated point mutations within the voltage-gated sodium channel were undetected in the cDNA and gDNA of resistant strains or field populations. The whole-genome de novo assembly of a Korean resistant strain was performed (GCA_026262555.1), and 13 genomes of susceptible and resistant individuals were re-sequenced using field populations. Approximately 3,369,837 variants (SNPs and indels) were compared with our reference H. armigera genome, and 1,032,689 variants were identified from open reading frames. A resistance-specific CYP3 subfamily gene with five variants (CYP321A1v1-v5) was identified in the resistant strains, indicating the potential role of these variants in resistance. RNA-seq analysis identified 36,720 transcripts from 45 Illumina RNA-seq datasets of the fat body, gut, and the rest of the body. Differential gene expression analysis revealed some differently overexpressed detoxification enzyme genes in the resistant strains, particularly cytochrome P450 genes. This finding was consistent with the results of bioassay tests using PBO-based synergists, further supporting the role of detoxification enzymes in resistance. Therefore, H. armigera may acquire deltamethrin resistance through a combination of actions, including the overexpression of various detoxification enzymes, such as CYP3 subfamilies (CYP321A5) and cuticular proteins. The five variants of CYP321A subfamily identified in this study may serve as a basis for understanding insecticide resistance at the molecular level and can be applied as diagnostic markers for resistance. Key MessagesO_LIKnown resistance-related mutations were undetected in all the resistant strains or field populations. C_LIO_LINo specific resistance-associated variations were identified at the genomic level. C_LIO_LIThe expression pattern of the CYP3 subfamily genes was strongly correlated with the level of resistance. C_LIO_LIGenes other than CYP337B3 are also involved in the development of high-level resistance. C_LIO_LIResistance developed as a result of changes in the expression of detoxification genes rather than target site modification through mutation. C_LI

ecology↗