Biology subjects

Yamamoto, K.

Publications and source records attributed to Yamamoto, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Asymmetric turnover dynamics of Nav1.6 voltage-gated sodium channels at the axon initial segment

Nav1.6 voltage-gated sodium channels are critical for shaping action potentials, and their precise localization at the axon initial segment (AIS) is essential for neuronal excitability. However, the turnover mechanisms that maintain this spatial pattern remain unclear. Here, we present a genetically engineered mouse in which endogenous Nav1.6 carries a Cre-switchable fluorescent tag, enabling us to simultaneously trace the turnover of pre-existing and newly synthesized Nav1.6 without perturbing AIS structure. Using this system, we determine the physiological lifetimes of Nav1.6 at the AIS in vivo and in vitro, and further uncover the spatially asymmetric turnover dynamics, with the proximal and distal AIS organizing a source-to-sink gradient. Based on the quantified parameters, computational modeling clarifies that this asymmetry promotes efficient clearance of older molecules, thereby supporting AIS quality control. Collectively, these findings provide a technical and conceptual foundation for understanding how molecular turnover contributes to AIS homeostasis.

neuroscience↗

bioRxiv2026

CATaN maps gene regulatory programs that shape genetic risk across complex diseases

Causal variants of complex traits are enriched at transcription factor (TF) binding sites and are thought to contribute to pathology by disrupting TF activity and thereby causing transcriptome dysregulation. However, existing approaches typically address TF-mediated gene regulatory networks (TF-GRNs) and transcriptomes separately, and methods that jointly leverage both to systematically assess disease heritability remain limited. We aimed to develop a framework that jointly leverages TF-GRNs and transcriptomes to assess disease heritability. Here, we constructed a matrix encoding TF-GRNs and developed an unsupervised analytical pipeline, Canonical correlation Analysis of Transcriptome and TF-gene regulatory Networks (CATaN). CATaN applies canonical correlation analysis (CCA) to extract canonical correlation (CC) components, i.e., shared variation components between transcriptomes and TF-GRNs, and converts them into genome-wide functional annotation scores connected to stratified LD score regression (S-LDSC) for heritability analysis. We applied CATaN to eight datasets, including 19,198 bulk samples and 611,772 single cells from human and mouse sources, identifying 588 CC components that are significantly enriched for SNP heritability across 69 complex traits. Notably, functional annotation tracks based on these TF-GRNs are distinct from transcriptome signatures prioritized by LDSC-SEG, with greater heritability enrichment for a subset of traits. Finally, we suggest that CATaN may help prioritize candidate causal variants for experimental fine-mapping using genome editing. Together, integrating TF-GRNs with transcriptomes reveals disease-relevant regulatory programs that are not fully captured by transcriptome-based analyses alone.

genetics↗

bioRxiv2026

A senescent iCAF-like fibroblast state governs therapy resistance in rheumatoid arthritis

ObjectivesRheumatoid arthritis (RA) synovitis frequently persists despite cytokine-targeted therapies, suggesting the existence of pathogenic stromal programs that sustain chronic inflammation independently of canonical immune pathways. Although synovial fibroblasts (SF) are increasingly implicated in treatment resistance, the pathogenic fibroblast states driving refractory disease and their therapeutic vulnerabilities remain poorly defined. MethodsWe integrated multimodal single-cell and spatial profiling of synovial tissue from 54 patients with RA with prospective treatment-response data and functional studies in human fibroblasts and experimental arthritis models. ResultsWe identified a C-X-C motif chemokine 12 (CXCL12)hi Apolipoprotein C1 (APOC1)+ fibroblast population selectively enriched in treatment-refractory synovitis. Spatial analyses demonstrated that these fibroblasts establish CXCL12-dependent plasmablast niches within inflamed synovium, resembling inflammatory cancer-associated fibroblasts (iCAF) that orchestrate immune cell recruitment in the tumor microenvironment. CXCL12hi APOC1+ fibroblasts exhibited a senescence-associated iCAF-like transcriptional program characterized by STAT3-C/EBP activation and APOC1 expression and were associated with poor response to TNF and IL-6 pathway inhibition. Mechanistically, APOC1 knockdown in RA-SF attenuated invasive mesenchymal behavior and disrupted senescence-associated inflammatory programs, identifying APOC1 as a central regulator of pathogenic fibroblast reprogramming. Importantly, genetic or pharmacological elimination of senescent cells ameliorated experimental arthritis and enhanced the efficacy of TNF blockade. ConclusionsThese findings implicate iCAF-like fibroblasts with senescent properties as a mechanistic driver of refractory RA synovitis and highlight stromal senescence programs as preclinically actionable therapeutic targets beyond cytokine inhibition.

immunology↗

bioRxiv2026

Ecological Role of the Heterotrophic Protist Aurantiochytrium (Labyrinthulomycetes) as a Key Consumer of Viral-Induced Dissolved Organic Matter Following the Lysis of the Red Tide-forming Microalga Heterosigma akashiwo

Marine algal blooms play a vital role in oceanic carbon cycling, yet the ecological consequences of algal organic matter released following their collapse via viral infection are poorly understood. Recent studies have shown that viral infection dramatically alters the hosts intracellular metabolite composition, and the subsequent viral lysate selectively promotes the growth of specific prokaryotic populations. This study aimed to elucidate the effect of organic matter derived from healthy and virus-infected cells of the bloom-forming alga Heterosigma akashiwo on the growth of heterotrophic eukaryotes, specifically Labyrinthulomycetes. These marine protists are primarily saprotrophic or predatory and contribute to dissolved organic matter (DOM) decomposition and nutrient cycling. Our field monitoring in Osaka Bay over 12 months revealed that while the overall Labyrinthulomycetes community showed no clear seasonality, specific populations of the protists co-occurred with Heterosigma akashiwo. To mechanistically investigate the potential trophic linkage suggested by these field observations, a co-culture system comprising H. akashiwo, its specific virus (HaV53), and Aurantiochytrium sp. NBRC102614, used here as a model Labyrinthulomycete, was established. In the co-culture experiments, viral lysis of H. akashiwo led to a significant increase in the cell density of Aurantiochytrium sp., demonstrating that Aurantiochytrium can thrive on substrates derived from the virus-infected alga, such as viral-induced dissolved organic matter (vDOM). These findings highlight that heterotrophic Labyrinthulomycetes are one of key consumers of virus-modified organic matter, playing a pivotal role in carbon cycling following the collapse of harmful algal blooms and influencing carbon transfer in coastal microbial food webs. IMPORTANCEMarine ecosystems are tightly regulated by the interplay between microalgae, viruses, and heterotrophic eukaryotes, yet their roles within this network have long been underestimated. Accordingly, this study aimed to provide an overview of the dynamics of environmental microalgae and heterotrophic eukaryotes, namely Heterosigma species and Labyrinthulomycetes, and to elucidate the impact of virus-infected Heterosigma akashiwo on the growth and proliferation of Aurantiochytrium species within heterotrophic Labyrinthulomycetes. This study revealed the dynamics of several Labyrinthulomycetes species associated with Heterosigma populations in coastal marine environments and demonstrated that Aurantiochytrium species have the capacity to redistribute carbon, such as by utilizing vDOM released during the termination of Heterosigma blooms via viral infection, thereby repositioning Aurantiochytrium from a passive component of Heterosigma viral infection toward an active ecological agent that facilitates energy transfer and contributes to the maintenance of microalgal community dynamics. Overall, this work provides new insights into the fate of virus-infected Heterosigma in coastal marine systems mediated by heterotrophic Labyrinthulomycetes, particularly Aurantiochytrium species, thereby filling an important knowledge gap in microbial ecology.

microbiology↗

bioRxiv2026

The significance of sukumo (composted indigo leaves) as a microbial source for traditional Japanese indigo dyeing

A critical process in traditional Japanese indigo dyeing is the microbial reduction of indigo within the dye suspension, which consists solely of sukumo (fermented indigo leaves), wood ash lye, and microbial nutrients such as wheat bran. Although sukumo has long been recognized as a potential microbial source, the microbial community dynamics during its production is still largely unexplored, and its contribution to dyeing performance via microbial supply remains poorly characterized. In this study, we investigated the significance of sukumo as a microbial source, in addition to its established role as a pigment source. We conducted a time-series analysis of microbial communities throughout the four-month fermentation process of sukumo, using weekly samples collected from two geographically distinct indigo dyeing studios. Microbial profiling revealed similar successional patterns between the two sites. Notably, in the later stages of fermentation, known indigo-reducing bacteria, such as the genus Oceanobacillus and the family Tissierellaceae, emerged at both locations. Laboratory-scale dyeing experiments using immature sukumo demonstrated that supplementation with a small amount of mature sukumo restored dyeing activity and increased the abundance of Oceanobacillus and Tissierellaceae. Furthermore, the addition of the indigo-reducing isolate Tissierellaceae strain TU-1 to the immature sukumo-based dye suspension led to a marked enhancement in dyeing performance. These findings highlight the critical role of sukumo as a microbial source in traditional indigo dyeing and suggest that prolonged fermentation is essential for nurturing functional indigo-reducing bacteria. This insight provides a foundation for improving dye suspension performance through targeted microbial community management.

microbiology↗

bioRxiv2025

Cellular and molecular fine mapping pinpoints new immunopathology of lupus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with an unknown etiology. To pinpoint new disease-relevant cell states and their molecular profiles, we performed an in-depth investigation of multimodal single-cell datasets comprising [~]2.1 million peripheral blood mononuclear cells from 346 donors. By resolving 123 fine-grained cell states across 27 cell types, we identified previously uncharacterized populations distinctively associated with clinical severity and treatment status, including GZMK+GZMH+HLA-DR+ effector memory CD8+ T cells (double-positive [DP] EMCD8) and FOXO1+ARHGAP15+ T cells. Through extensive statistical frameworks and multimodal approaches, we delineated their aberrant immune signaling networks, transcriptional regulators, key surface proteins, T cell receptor repertoires, and genetic/epigenetic landscapes, underscoring them as candidate drivers of SLE immunopathology. These findings provide new insights into therapeutic target discovery in SLE.

immunology↗

bioRxiv2025

A blue light receptor CRY1 regulates de novo shoot regeneration

Tissue culture enables plant transformation and gene editing, yet inefficient regeneration remains a major bottleneck, and the downstream circuitry linking light perception to tissue culture has not been investigated. Here we demonstrate that the blue-light photoreceptor CRYPTOCHROME 1 (CRY1) enhances Arabidopsis thaliana shoot regeneration in a blue light dependent manner. In a two-step root-to-shoot tissue culture system, cry1 mutant exhibits reduced shoot regeneration. Transcriptomic analyses in the cry1 mutant reveal that CRY1 suppresses the expression of AUXIN RESPONSE TRANSCRIPTION FACTOR 3 (ARF3). Consistently, arf3 mutant exhibits enhanced shoot regeneration phenotype. Additionally, genetic and protein interaction assays show that ARF3 acts downstream of CRY1 at both transcriptional and post-translational levels. Furthermore, transcriptomic analyses in the arf3 mutant show that ARF3 activates salicylic acid (SA)-responsive genes that suppress shoot formation, and exogenous SA inhibits regeneration in arf3 calli. Integrating RNA-seq with cis-motif analysis identifies stress-responsive ARF3 targets within the CRY1 network. Our results establish a novel CRY1-ARF3 regulatory module that links blue-light perception to hormonal signaling during regeneration, revealing how plants integrate environmental cues with growth-defense trade-offs. SynopsisThe blue-light photoreceptor CRY1 promotes de novo shoot regeneration in Arabidopsis thaliana by restraining ARF3-mediated SA signaling. It reveals a fundamental trade-off between defense responses and regenerative growth in plants, coordinated by CRY1-ARF3 module. O_LICRY1-mediated blue light signaling enhances de novo shoot regeneration from callus. C_LIO_LIARF3 acts downstream of CRY1 and CRY1 physically interacts with ARF3. C_LIO_LIARF3-activated SA pathway represses shoot regeneration. C_LIO_LICRY1 enhances shoot regeneration by suppressing ARF3-activated stress responsive genes. C_LI

plant biology↗

bioRxiv2025

CRISPR/Cas9-mediated genome editing reveals the involvement of a polyphenol oxidase in the shikonin-specific biosynthesis in Lithospermum erythrorhizon

Shikonin, a 1,4-naphthoquinone derivative produced by several Boraginaceae species, exhibits unique pharmacological properties and is used as a natural dye. The regulatory factors of shikonin production have been demonstrated using a cell culture system of Lithospermum erythrorhizon. Among these factors, copper is known to be the strongest enhancer of shikonin production. Although shikonin biosynthesis has been studied for over 40 years, the steps of naphthalene ring formation are still unknown, as is the reason for the effect of copper. In this study, we explored candidate genes associated with shikonin production using a PCR-select subtraction experiment. Polyphenol oxidase (PPO), a dicopper-dependent oxidoreductase, was highlighted because it showed synchronous expression with shikonin production. Transcriptome analysis of hairy roots and cultured cells of this plant revealed that, of the five PPO genes expressed in L. erythrorhizon, only PPO1 showed a strong correlation with shikonin production. Next, we generated genome-edited hairy roots of LePPO1 using CRISPR/Cas9-mediated mutagenesis to analyze its impact on shikonin derivative and other specialized metabolite production. The results showed that shikonin content was markedly reduced in all LePPO1-ge lines. Interestingly, the content of deoxyshikonofuran, a hydroquinone derivative and shunt product that branches after GHQ-3''-OH in the shikonin biosynthetic pathway, remained unaffected in the LePPO1-ge lines. These findings suggest that LePPO1 participates in naphthalene ring formation and explain why a copper ion is crucial for shikonin biosynthesis.

biochemistry↗

bioRxiv2025

Problem-solving without a cortex: inferior lobe drives goal-directed object manipulation in cichlid fish

Goal-directed object manipulation and problem-solving, which are necessary to evolve tool use behaviors, have long been linked to the expansion of the telencephalon in mammals and birds. Here, we show that goal-directed object manipulation in cichlid fish is driven by a non-telencephalic brain structure, the inferior lobe. Using manganese-enhanced MRI (MEMRI) on an ultra-high field 17.2 Tesla MRI system, we show that the inferior lobe is activated during a puzzle-box opening task. Furthermore, magnetic resonance (MR)-guided High Intensity Focused Ultrasound (HIFU) lesions profoundly impair fine motor coordination during this task without affecting general locomotion or motivation. These results reveal that cortex-like cognitive functions can arise from non-telencephalic brain structures in teleosts. With no homolog in tetrapods, the inferior lobe is a critical hub for flexible behavior in teleost fish. Our findings highlight the existence of alternative neural architectures for the emergence of complex cognition.

neuroscience↗

bioRxiv2025

Scaffold-free cryopreservable cartilage grafts obtained from hiPSC-derived chondroprogenitor cells for airway reconstruction with growth adaptability

Pediatric tracheal reconstruction remains a major clinical challenge because of limited graft availability and the need for growth-adaptive materials. Current approaches, such as costal cartilage grafting and use of scaffold-based constructs, often suffer from complications including graft resorption, donor site morbidity, and poor integration. Here, we present scaffold-free cartilage grafts (chondro-plates) derived from expandable limb-bud mesenchymal cells generated from human leukocyte antigen-homozygous human induced pluripotent stem cells. These grafts are cryopreservable and maintain their hyaline cartilage phenotype after a brief pre-culture. In both rat and rabbit tracheal defect models, chondro-plates supported robust cartilage regeneration, epithelial reconstitution, and neovascularization. Importantly, in a pediatric-like growing rat model, chondro-plates preserved luminal patency and structural integrity, outperforming autologous costal cartilage. This study demonstrates a clinically viable, off-the-shelf strategy for tracheal reconstruction using scalable, immunocompatible, and growth-adaptive cartilage grafts.

bioengineering↗

bioRxiv2025

Functional Brain Imaging and Targeted Lesion Studies Using Manganese-Enhanced MRI and Focused Ultrasound in Non-Conventional ModelSpecies

Linking behavior to its neuroanatomical basis in non-conventional model species remains a significant challenge due to the scarcity of imaging and molecular tools. Commonly used approaches such as electrophysiological recordings rely on precise stereotaxic atlases or species-specific antibodies, while optogenetics requires transgenic lines which are largely unavailable beyond classical model organisms (e.g., mice, rats, zebrafish). Moreover, surgical lesion studies, a staple for verifying brain structure and behavior relationships, are logistically complex in species lacking atlases or living in aquatic environments. Here, we present a protocol integrating Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) and MR-guided High-Intensity Focused Ultrasound (HIFU) to overcome these limitations, which we demonstrate in the convict cichlid (Amatitlania nigrofasciata), a teleost fish lacking conventional neuroscience tools. MEMRI enables non-invasive, sub-millimeter resolution mapping of brain activity during behavior, and HIFU facilitates precise, surgery-free lesioning of targeted regions, adaptable to species without stereotaxic atlases. This combined approach offers a versatile, broadly applicable framework for linking brain structure and behavior in non-model organisms, advancing evolutionary and comparative neuroscience.

neuroscience↗

bioRxiv2025

Metabolism of L-threonate, an ascorbate degradation product, requires a protein with L-threonate metabolizing domains in Arabidopsis

L-Threonate is one of the major degradation products of ascorbate in plants. While bacteria can utilize L-threonate as a sole carbon source by converting it to dihydroxyacetone phosphate, a glycolysis intermediate, through a three- or four-step metabolic pathway, the corresponding processes in plants remain uncharacterized. Remarkably, an Arabidopsis gene encodes a unique protein containing domains homologous to all three enzymes involved in the bacterial three-step pathway. We designated this protein as L-threonate metabolizing domains (LTD) and investigated its functional role in plant L-threonate metabolism. Despite extensive efforts, recombinant expression of LTD was unsuccessful, likely due to its large protein size. Therefore, a reverse genetic approach was employed, using ltd knockout Arabidopsis lines to explore LTD function. Under continuous dark conditions, where ascorbate degradation is facilitated, LTD transcription was significantly upregulated, leading to increased L-threonate dehydrogenase (LtnD) activity. Knockout lines of LTD exhibited no detectable LtnD activity under both light and dark conditions, alongside elevated levels of L-threonate compared to wild-type plants. These results indicate that LTD is essential for L-threonate metabolism in Arabidopsis. The LTD gene is highly conserved among land plants but is absent in green algae, providing a hypothesis that the rise in ascorbate concentrations during plant evolution necessitated a more active metabolism of ascorbate degradation products.

plant biology↗

bioRxiv2025

Improved Tumor Blood Flow Enhances the Abscopal Effect: Preclinical Assessment in Mice Treated with Combined Radiation and PD-1 Blockade Therapy

The abscopal effect, where localized radiation therapy induces regression of distant metastatic lesions through immune activation, shows promise for treating metastatic cancer but occurs inconsistently. Here we demonstrate that tumor perfusion critically influences systemic immune responses to combination therapy with radiation and PD-1 blockade. Using multimodal imaging including DCE-MRI, EPR oximetry, and hyperpolarized 13C-MRI, we show that successful abscopal responses in MC38 tumors are characterized by enhanced perfusion, reduced hypoxia, decreased cellularity, and lower glycolytic activity in remote tumors. Notably, pre-treatment perfusion metrics (AUC1min) and extracellular volume (AUC10min) in primary tumors predict subsequent growth of remote tumors, while the same measurements in remote tumors lack predictive value. Based on these findings, we enhanced the abscopal effect by exposing mice to carbogen (95% O2 + 5% CO2) during radiation therapy. Carbogen exposure increased tumor perfusion by 71% (AUC1min) and significantly improved systemic responses in the checkpoint blockade responsive MC38 model but not in the poorly responsive B16.F10 tumors. The enhanced response correlated with increased activation of CD8+ T cells in tumor-draining lymph nodes and elevated serum HMGB-1 levels. RNA sequencing revealed significant extracellular matrix remodeling in carbogen-treated tumors. These results establish tumor perfusion as both a predictive biomarker and a modifiable determinant of systemic immune responses, suggesting that perfusion-based patient stratification and vascular modification strategies could improve outcomes in combination immunotherapy and radiation treatment.

cancer biology↗

bioRxiv2025

The phenotypic variation of widefins medaka is due to the insertion of a giant transposon containing a viral genome within hoxca cluster

Phenotypic variation in species arises from genetic differences and environmental influences on gene expression. Differences in epigenetic modifications, such as histone modifications and DNA methylation, can also contribute to phenotypic variations, even among individuals with identical genetic information. However, the underlying molecular mechanisms are not yet fully understood, particularly in vertebrates. The number of fin rays in teleosts, such as medaka, serves as a useful model for studying this variation. In a previous study, we demonstrated that the teleost Hox code plays a crucial role in determining the anterior-posterior identity necessary for the formation of dorsal and anal fins. In this study, we investigated widefins medaka, a spontaneous mutant displaying phenotypic variation in the number of dorsal and anal fin rays. Long-read whole-genome sequencing revealed that an extremely large transposon, Teratorn, containing a herpesvirus genome, was inserted into the hoxc12a 3 UTR. This insertion decreased hoxc12a expression and, in some cases, also affected neighboring hox genes, resulting in variations in fin size and the presence or absence of dorsal fins. Additionally, hoxc6a, located 50 kb away from the insertion, was also downregulated in widefins medaka. These findings suggest that this large transposon insertion leads to a reduction in nearby hox gene expression, contributing to the phenotypic variation observed in widefins medaka. These results highlight the role of transposable elements and epigenetic regulation in generating phenotypic diversity in vertebrates.

genetics↗

bioRxiv2025

Development of CRISPR/Cas13-based analytical tools to study RNA-Protein Interactions

RNA-protein interactions (RPIs) are as important as protein-protein interactions (PPIs) for the formation of membraneless organelles (MLOs) and play a vital role in various biological processes. Despite remarkable advances in PPI analysis technologies in recent years, the development of RPI analysis tools has lagged behind. To advance RPI analysis, we integrated three established PPI tools--bimolecular fluorescence complementation (BiFC), NanoBiT, and split-TurboID--with the RNA-targeting CRISPR/Cas13. We applied these tools to analyze paraspeckles, one of the best known MLOs formed by interactions between the long non-coding RNA NEAT1 and the RNA-binding protein NONO. The optimized BiFC-dCas13 allows live cell imaging and quantitative detection of the NEAT1-NONO interaction. The NanoBiT-dCas13 detects dynamic changes in the NEAT1-NONO interaction in an immediate and reversible manner. As a proximity labeling tool, the Split-TurboID-dCas13 induces biotinylation of proteins surrounding paraspeckles, leading to the identification of the N6-methyladenosine reader protein YTHDC1 as a novel paraspeckles-associated protein. The BiFC-dCas13, NanoBiT-dCas13, and Split-TurboID-dCas13 systems have a broad utility for the analysis of RPIs and MLOs.

bioengineering↗

bioRxiv2025

Structural basis of a phosphotransferase system xylose transporter

The bacterial phosphotransferase system (PTS) is essential for carbohydrate uptake, and IIC transporters in the system facilitate intracellular sugar transport. Here, we report the crystal and cryo-EM structures of Leminorella grimontii GatC (LgGatC), a putative xylose transporter in the IIC family, in its outward-facing state. Structural analysis indicates that the outward-facing cavity recognizes the linear form of D-xylose. A structure-based homology model of an inward-facing state supports an elevator-like sugar transport mechanism. These findings provide insights into PTS-mediated xylose transport and its potential applications in microbial engineering.

molecular biology↗

bioRxiv2025

Foliar ascorbate degradation in the dark occurs independently of ascorbate peroxidase/oxidase, recycling enzymes, and senescence signaling

Ascorbate is a key antioxidant that protects plant cells from oxidative damage. While plants actively synthesize ascorbate during the day, its degradation becomes prominent under prolonged dark conditions. Since ascorbate degradation begins with its oxidized form, dehydroascorbate (DHA), this process inherently requires ascorbate oxidation. However, the molecular mechanisms underlying dark-induced ascorbate oxidation and subsequent degradation remain unclear. In this study, we investigated the role of intracellular and extracellular ascorbate redox regulation in controlling this process. Using Arabidopsis knockout mutants for key enzymes involved in ascorbate oxidation and recycling, including ascorbate peroxidase (APX), monodehydroascorbate reductase (MDAR), dehydroascorbate reductase (DHAR), and ascorbate oxidase (AO), as well as NADPH oxidases (rbohD and rbohF), we found that none of these enzymes significantly influenced the dark-induced decrease in ascorbate levels. Notably, ascorbate levels decreased similarly in newly generated multiple mutants, including a quintuple mutant ({Delta}dhar pad2 mdar5), which has severely impaired ascorbate recycling capacity, and the ao2 rbohD double mutant, which is strongly expected to exhibit a highly altered apoplastic redox state. Furthermore, we examined the potential involvement of senescence signaling, including ORESARA1 and ethylene signaling components, but found no evidence for their contribution. These findings indicate that the dark-induced decrease in ascorbate levels is not governed by conventional pathways for ascorbate oxidation and recycling or senescence signaling processes, suggesting an unidentified regulatory mechanism.

plant biology↗

bioRxiv2025

BMP-Dependent Mobilization of Fatty Acid Metabolism Promotes Caenorhabditis elegans Survival on a Bacterial Pathogen

The Bone Morphogenetic Proteins (BMPs) are secreted peptide ligands of the Transforming Growth Factor beta (TGF-{beta}) family, initially identified for their roles in development and differentiation across animal species. They are now increasingly recognized for their roles in physiology and infectious disease. In the nematode Caenorhabditis elegans, the BMP ligand DBL-1 controls fat metabolism and immune response, in addition to its roles in body size regulation and development. DBL-1 regulates classical aspects of innate immunity, including the induction of anti-microbial peptides. We theorized that BMP-dependent regulation of fat metabolism could also promote resilience against microbial pathogens. We found that exposure to a bacterial pathogen alters total fat stores, lipid droplet dynamics, and lipid metabolism gene expression in a BMP-dependent manner. We further showed that fatty acid desaturation plays a major role in survival on a bacterial pathogen, while fatty acid {beta}-oxidation plays a more minor role. We conclude that C. elegans mobilizes fatty acid metabolism in response to pathogen exposure to promote survival. Our investigation provides a framework to study potential metabolic interventions that could support therapeutics that are complementary to antibiotic strategies.

physiology↗