Biology subjects

Liu, Y.

Publications and source records attributed to Liu, Y..

At least 91 records · Page 5Linked to original sources

bioRxiv2026

Maleic acid adjuvates BCG to induce CD4+CD8+ T cells and sterilize tuberculosis

Anti-tuberculosis (TB) immunity typically emphasizes CD4+ T and CD8+ T cells that only provide limited protection against Mycobacterium tuberculosis (Mtb) infection. The anti-TB function of CD4+CD8+ T cells remains unexplored, mostly due to the dogma that ThPOK and Runx3 antagonize each other to block their development and their scarcity. Here, we show that immunization of BCG (Bacillus Calmette-Gu&eacuterin) with Complete Freund's Adjuvant (CFA) markedly induced CD4+CD8+ T cells through the gut microbiota Clostridium butyricum or its metabolite maleic acid. Mtb-specific CD4+CD8+ T cells exhibited a broad T-cell receptor repertoire and sterilized Mtb infection by inducing SLAMF1 and neutrophil responses. Mechanistically, maleic acid interacted with PAK2 to promote STAT5 phosphorylation at Ser127, thus upregulating Ets1 expression. Direct binding of Ets1 to the Runx3 and ThPOK promoters orchestrated their expression to redirect the CD8+ T cell differentiation towards the CD4+CD8+ lineage. Moreover, immunization of BCG plus Clostridium butyricum or maleic acid sterilized Mtb infection in mouse models. These findings establish CD4+CD8+ T cells as superior immune effectors against Mtb, a concept that could fundamentally redirect the current paradigm for anti-TB vaccine development.

microbiology↗

bioRxiv2026

The Impact of TOR-S6K-eIF5A Signaling on Translational Control is Key to Plant Root Development

Nutrient-responsive Target of Rapamycin (TOR)-S6 kinase (S6K) signaling coordinates plant growth with protein synthesis, but how it interfaces with translation elongation to produce specific developmental outputs remains unclear. Here, we identify eukaryotic translation factor 5A (eIF5A) as an S6K-associated phosphoprotein in Arabidopsis thaliana. S6K1 and S6K2 associate with all three eIF5A isoforms and phosphorylate them in vitro, with Ser2 emerging as the major S6K1-responsive site in eIF5A-2. The corresponding N-terminal serine is invariant across the analyzed Archaeplastida eIF5A proteins. Conditional depletion of TOR, S6K1/2, or eIF5A produces overlapping reductions in primary root length and root hair coverage. eIF5A depletion leaves bulk protein synthesis and polysome profiles largely unchanged while selectively decreasing output from deca-proline reporters. Reporter activity is restored by amiRNA-resistant wild-type and phosphomimetic S2D eIF5A-2, whereas S2A does not restore activity, demonstrating the functional importance of the Ser2 state. Proteomic profiling identifies a restricted set of eIF5A-responsive proteins, and five of six tested insertion mutants display altered primary root growth, root hair coverage, or both. Together, these findings uncover a regulatory connection between S6K and eIF5A and establish eIF5A-dependent selective translation as a mechanism contributing to root development in A. thaliana.

molecular biology↗

bioRxiv2026

Light Guiding in Scattering Media Using Focused Laser-Induced Acoustic Waves with an Open Elliptical Reflector

Light scattering in biological tissue limits deep optical imaging. Acoustic waves can modulate optical properties and enhance photon delivery, but source-positioning requirements can complicate integration with other imaging modalities. Here, we present an open elliptical reflector that focuses laser-induced acoustic waves at a spatially separated target while maintaining open optical access. We characterized the spatiotemporal optical modulation induced by the localized acoustic focus. The system increased the local transmitted-light intensity by a factor of 2.57-fold through a 2-mm-thick 1% intralipid hydrogel and enhanced fluorescence signal under two-photon excitation through a 1.5-mm-thick scattering sample. These results demonstrate spatially separated, reflector-based acoustically assisted light guiding for enhanced light delivery and fluorescence excitation through scattering media.

bioengineering↗

bioRxiv2026

The PSInet Plant Water Potential Database: advancing new perspectives on plant water status, traits, and hydraulic processes

Water potential gradients drive water flow within and between soils and plants, and the internal plant water potential controls a wide range of physiological processes including photosynthesis, growth, and mortality. Notwithstanding this clear relevance for many critical aspects of ecosystem function, water potential data have historically been relatively inaccessible and unnetworked. The absence of a centralized repository for plant water potential time series limits our ability to integrate a wealth of ecophysiological information from other networks and from remote sensing. Closing this gap is necessary to address unresolved questions about plant responses to drought and heat stress, and to make confident predictions about plant and ecosystem function in a warming world. Here, we introduce the PSInet database -- a global collection of plant water potential time series from 285 datasets representing 523 species. We present the workflow that guided database development and evaluate its key features. Through a series of preliminary analyses, we then highlight the potential of the PSInet database for applications including: a) advancing plant water use strategy frameworks; b) disentangling the impacts of soil versus atmospheric drought stress; c) assessing the long-held assumption of pre-dawn equilibration of ecosystem water potential; d) understanding the risk of drought-driven mortality; and e) benchmarking remote-sensing data products and land-surface models.

plant biology↗

bioRxiv2026

Risk-Window Palbociclib Exposure Delays ErbB2-Driven Mammary Tumorigenesis and Suppresses Mammary Epithelial Cell Stemness

ErbB2 overexpression occurs in 15-20% of invasive breast cancer (BC) and inactivation of Cyclin D1-CDK4/6 axis reduce mammary stem/progenitor cells in ErbB2-driven tumorigenesis. Here, we explored the preventive role of short-term palbociclib intervention in MMTV-ErbB2 mice. Palbociclib significantly inhibited the proliferation and stemness of ErbB2-overexpressed BC cells in vitro and in vivo. Furthermore, short-term palbociclib exposure during the early premalignant risk window significantly delayed mammary tumor development and reduced tumor multiplicity, accompanied by the suppression of epithelial proliferation and ductal/alveolar morphogenesis in premalignant tissues, as well as prolonged tumor-free survival compared with controls. Importantly, palbociclib reduced the luminal epithelial (CD24high/CD49flow), mammary reconstitution unit-enriched (CD24high/CD49fhigh) subpopulations, and luminal progenitor/TIC-enriched (CD61high/CD49fmid) subpopulations. These changes were accompanied by diminished mammary epithelial cell stemness functions, including colony-forming, mammosphere-forming, and 3D growth activities of mammary epithelial cells. Mechanistically, palbociclib-treated tissues showed inhibition of the Cyclin D1-CDK4/6-RB-E2F axis and coordinated attenuation of ER-, ErbB2- and Wnt/{beta}-catenin-associated signaling. Together, we demonstrate that short-term CDK4/6 inhibition during a premalignant risk window produces a sustained delay in ErbB2-driven mammary tumorigenesis, associated with remodeling of the mammary epithelial hierarchy and suppression of proliferative and stem/progenitor-associated activity, suggesting CDK4/6 inhibition as a strategy for ErbB2-positive BC prevention.

cancer biology↗

bioRxiv2026

Multi-Omics analysis provides crucial insights into ecological adaptation to dryland of a dominant grass (Psammochloa villosa, Poaceae) in Northwest China

Desertification exerts dramatic selection pressures on the evolution of plants. Despite the key role of ecological adaptation by natural selection to arid grasslands and subsequent intraspecific divergence, specific mechanisms driving this process remain poorly understood. Psammochloa villosa, a perennial forage grass endemic to the arid grasslands in Northwest China, where it thrives in shifting and semi-fixed sand land due to its exceptional drought tolerance, provides an ideal system to study adaptive evolution to aridity. In our study, we assembled a high-quality, chromosome-scale genome and conducted genomic resequencing of 42 populations across its major distribution. The genome assembly, which is approximately 1.55 Gb in size, has a super-scaffold N50 of 66.79 Mb, with 75.84% of the sequences identified as transposable elements. Coalescent phylogeny and genomic collinearity analyses strongly supported that P. villosa and Neotrinia splendens, as the closest taxa, shared a recent whole-genome duplication (WGD) event occurring approximately 18-20 Mya and followed by their divergence around ~11.2 Mya. Based on ancestral grass karyotype (AGK) reconstruction from synteny analysis, our results suggest that, relative to the AGK after the {rho}-WGD event, P. villosa and N. splendens underwent similar chromosomal restructuring and lineage-specific retention of numerous copies, providing a genomic basis for potential ecological adaptation and intraspecific diversification. The expanded XTH family, which encodes enzymes mediating xyloglucan endotransglucosylation and hydrolysis and thereby regulating xyloglucan remodeling, showed strong transcriptional responses under PEG-6000 treatment, suggesting that retained copies may be associated with xerophytic adaptation in P. villosa. Together, these findings suggest that WGD-derived gene retention created a delayed reservoir of genetic diversity that was later shaped by desertification and Qinghai-Xizang Plateau environmental changes, contributing to climate-associated genomic islands and intraspecific differentiation.

genomics↗

bioRxiv2026

Integrated Transcriptomics and Histological Analysis Reveals Gill Adaptation Mechanisms to Hypoxic Stress in Largemouth Bass (Micropterus salmoides)

Largemouth bass (Micropterus salmoides) is a globally significant freshwater aquaculture species known for its rapid growth, high-quality flesh, and excellent nutritional value. Given the increasing incidence of hypoxia in its aquaculture setting, understanding the molecular mechanisms underlying gill adaptation to hypoxic stress is critical for improving resilience in this species. To achieve this, we employed full-length transcript sequencing using PacBio Iso-Seq and high-throughput Illumina RNA-seq to construct a comprehensive transcriptome profile. Histological analyses revealed apparent structural alterations in gill tissues under hypoxic stress (dissolved oxygen: 2.0 +/- 0.5 mg/L, duration: 96 h), including curved and swollen gill filaments, apoptosis, and epithelial cell vacuolation. Comparative transcriptomic analysis revealed pronounced shifts in the expression of genes involved in energy metabolism, angiogenesis, immune responses, cell proliferation, and apoptosis. Notably, the down-regulation of genes associated with cell cycle and proliferation suggests that M. salmoides may conserve energy by suppressing cell division under hypoxic conditions. In contrast, the increased expression of apoptosis-related genes, including Caspase 7, indicates that apoptosis may play a protective role to maintain tissue homeostasis under hypoxia. Furthermore, the suppression of chemokine-mediated immune pathways implies that hypoxia redirects energy toward essential metabolic processes at the cost of local immune responses. GO and KEGG enrichment analyses identified TNF- and chemokine-mediated signaling pathways as key regulators for tissue homeostasis and adaptive responses to hypoxic stress. These findings enhance our understanding of the mechanisms underlying hypoxia adaptation and provide valuable genetic resources for breeding strategies aimed at enhancing hypoxia tolerance in M. salmoides.

genomics↗

bioRxiv2026

Estimand-aware and donor-aware triangulation of predefined gene-set signals across human tendon transcriptomic datasets

We analysed five predefined programmes across three human tendon transcriptomic contexts: acute exercise-associated fibroblast pseudobulks (E-MTAB-15400; 4 control and 4 exercise samples), mechanically stretched donor-derived cells (GSE150482; 3 normal and 3 tendinopathy donors), and paired lesional versus grossly normal-appearing tendon (GSE26051; 23 donor pairs). Inference was conducted at the sample, donor or donor-pair level. Non-stimulated GSE150482 single-cell RNA sequencing comprised only N1 and D1, whereas stretched single-cell RNA sequencing comprised N1-N3 and D1-D3; the conditions also used Drop-seq and 10X Chromium, respectively. A donor-replicated disease-by-stimulation interaction is therefore not estimable. Within-context Benjamini-Hochberg adjustment supported acute mechanical-response, extracellular-matrix (ECM) and protein-folding differences and paired-lesion collagen, integrin and ECM differences, but no stretched donor-background difference. Exact label permutations, a conservative global 15-test adjustment, leave-one-unit analyses, a Fib1-Fib4 pooled sensitivity and a paired exact Wilcoxon sensitivity qualified these findings. Integrin was fully nested in ECM, while collagen overlapped 52/79 genes with ECM. Collagen fibril organization showed the most directionally consistent matrix-associated pattern across the three non-equivalent contrasts, without establishing a disease-specific loading response or causal mechanism. The analysis demonstrates why public tendon datasets must be integrated by estimand and biological inference unit rather than pooled as interchangeable replications.

bioinformatics↗

bioRxiv2026

Precision cooling assists electrical stimulation: Breaking selectivity barriers in nerve control

Peripheral neuromodulation can relieve pain through sensory activation or conduction block. However, electrical stimulation of mixed nerves couples these intended effects to unwanted neural activity. Here we demonstrate local cooling can separate targeted from off-target neural activity. In the rat sciatic nerve, precooling reduced the onset response to kilohertz-frequency stimulation by about 90% and maintained block in the target pathway during rewarming. During low-frequency stimulation, spatially graded cooling suppressed A{delta} enriched activity and blocked nontarget propagation. This produced a directional, A{beta} biased afferent output. A cooling-electrical neural digital twin predicted both responses and linked them to field-edge transition dynamics and spatially separated control of recruitment and conduction. These findings provide a mechanistically grounded route beyond the targeting limits of electrical stimulation alone.

bioengineering↗

bioRxiv2026

An Oxidative Stress-Associated Seven-Gene Prognostic Signature in Lung Adenocarcinoma: Integrative Transcriptomic Analysis Across Public Cohorts

Lung adenocarcinoma is molecularly heterogeneous, and oxidative-stress programs can support either tumor restraint or tumor adaptation depending on cellular context. This study integrated public lung adenocarcinoma transcriptomic cohorts to identify oxidative-stress-associated expression features and evaluate their prognostic relevance. Expression profiles from The Cancer Genome Atlas, Genotype-Tissue Expression project, and GEO series GSE31210, GSE40791, and GSE30219 were analyzed. Differential expression, weighted gene co-expression network analysis, functional enrichment, univariable Cox regression, and least absolute shrinkage and selection operator Cox modeling were combined to derive a risk signature. Immune-cell enrichment, gene set enrichment analysis, gene set variation analysis, and pan-cancer analyses were used for biological characterization. A total of 1,305 genes differed between tumor and control samples, including 498 upregulated and 807 downregulated genes. Intersection of differentially expressed genes, the oxidative-stress-associated co-expression module, and the oxidative-stress gene set yielded 44 genes enriched in responses to reactive oxygen species and hydrogen peroxide, antioxidant and peroxidase activities, focal adhesion, Rap1 signaling, and PI3K-Akt signaling. A seven-gene signature comprising FBLN5, HBB, FYN, HGF, TFAP2A, PLIN5, and F2RL1 stratified the 523-sample training cohort and the 207-sample internal validation cohort into groups with different overall survival. Time-dependent areas under the receiver operating characteristic curve at 1, 3, and 5 years were 0.677, 0.622, and 0.649 in training and 0.613, 0.691, and 0.706 in internal validation. In the 85-case GSE30219 external cohort, corresponding values were 0.588, 0.661, and 0.631; survival separation followed the expected direction but did not reach statistical significance (log-rank P = 0.100). Seventeen immune-cell signatures differed between risk groups, while high-risk tumors were enriched for cell-cycle, DNA-replication, mismatch-repair, glycolytic, E2F, G2M-checkpoint, MYC-target, and mTORC1-related programs. The signature therefore captures reproducible oxidative-stress-associated transcriptional variation with moderate prognostic discrimination. Its clinical utility requires prospective evaluation, complete clinical adjustment, and experimental validation.

cancer biology↗

bioRxiv2026

Accurate and scalable decontamination of imaging-based spatial transcriptomics via optimal transport

Imaging-based spatial transcriptomics enables molecule-resolved profiling of gene expression and tissue organization in situ. However, segmentation errors, transcript spillover and three-dimensional cell overlap can introduce misassigned transcripts into cell-level expression profiles, compromising biological interpretation and obscuring genuine signals. Existing methods either remove suspect expression at the cost of signal loss or lack a biologically grounded criterion for transcript assignment. Here we present CellDot, an optimal-transport framework that determines the fate of each transcript by retaining it in its host cell, reassigning it to a plausible neighboring cell or removing it as background. By integrating reference-guided expression compatibility with spatial information and data-adaptive constraints, CellDot enables accurate and traceable molecule-level correction while preserving biologically meaningful variation. In evaluations across multiple human tumor datasets, CellDot exhibited superior performance compared to existing decontamination methods, successfully restoring spatial expression patterns that matched independent cross-platform measurements. Moreover, it significantly enhanced the recovery of cellular states, intercellular communication, and spatial niche programs. Our experiments using real data demonstrated CellDot's scalability and established it as the only method applicable to a whole-transcriptome Atera dataset, underscoring its distinct advantages in the field of spatial transcriptomics.

bioinformatics↗

bioRxiv2026

Revision of Paraglomeromycetes unveils a new order (Pervertustales), a new family (Innosporaceae), and a new genus (Opikia) in Glomeromycota

Currently, the fungal class Paraglomeromycetes (phylum Glomeromycota) consists of one order, Paraglomerales, with two families: Paraglomeraceae, comprising the genera Paraglomus with ten species and Innospora with one species, and the monogeneric and monospecific Pervetustaceae represented by Pervetustus with Pe. simplex. However, our morphological analyses of these species and an undescribed specimen morphologically resembling other Paraglomeromycetes species, as well as analyses of sequences of these fungi and environmental sequences, indicated that the current taxonomic composition of this class should be updated. We did so here by creating in Paraglomeromycetes Pervetustales ord. nov. with Pervetustus and Opikia catenata gen. nov. and sp. nov., as well as transferring Innospora with In. majewskii to Innosporaceae fam. nov. These novelties were introduced primarily based on strong genetic divergences of the analyzed taxa, as many morphological and histochemical features of their spores and mycorrhizal structures overlap. Only Op. catenata possesses the unique trait of occasionally producing spores in chains. This mode of sporulation has also not been recognized in any other Glomeromycota species. Unlike species of Pervetustales and Innosporaceae, which produce single-walled spores, the subcellular spore structure of Paraglomus species contains one or two walls.

microbiology↗

bioRxiv2026

Molecular Editing in Protein Degradation: From a Dual NSD2/GSPT1 Degrader to an NSD2-Selective PROTAC and a GSPT1-Selective Molecular Glue

Both NSD2 and GSPT1 represent compelling targets for anti-cancer drug discovery. Herein, we carried out single-atom modification of LLC0424, an NSD2 degrader with GSPT1 neosubstrate engagement, to yield two structurally analogous molecules with divergent modes of action: 424-ND, an NSD2-selective degrader, and 424-GD, a GSPT1-selective degrader. 424-ND drove selective NSD2 degradation and suppressed androgen receptor (AR) signaling in prostate cancer cells. 424-GD induced selective degradation of GSPT1 and upregulated the integrated stress response markers ATF4 and ATF3. Biolayer interferometry revealed distinct ternary complex cooperativity profiles in the presence of NSD2 or GSPT1, which directly correlate with the observed biased degradation activity. Molecular dynamics and metadynamics simulations showed that the compounds adopt distinct low-energy conformational ensembles with different spatial orientations, likely underlying their divergent cooperativity and selectivity. These findings demonstrate that minimal structural alteration permits precision control over degrader target selectivity, while furnishing selective chemical probes for NSD2 and GSPT1.

cancer biology↗

bioRxiv2026

scOLAR: Ontology-Anchored Open-Set Annotation of Single-Cell RNA-seq Data

Single-cell RNA sequencing profiles cellular heterogeneity at atlas scale, making automated annotation essential. However, target datasets often contain novel cell types missing from incomplete references. We present scOLAR, an ontology-guided open-set framework that learns prototypes over the Cell Ontology and uses both reference and target expression to annotate known classes while detecting unfamiliar populations. Guided by ontology hierarchies and decision-boundary regularization, scOLAR penalizes coarse-lineage misclassification and groups novel cells without requiring predefined cluster counts. Across benchmarks, scOLAR achieves a novelty-detection AUROC of 0.9726 and an average precision of 0.9871, enabling structured post-hoc lineage-level interpretation of populations absent from the reference.

bioinformatics↗

bioRxiv2026

Source of genome-wide deleterious variation in a global cattle cohort

Background Identifying deleterious DNA changes underpins efforts to improve animal health, welfare, and sustainable breeding. In cattle, current variant prioritization focuses on coding changes, uses single annotation types, and gives limited resolution in non-coding sequence. Results We developed BovCADD (bovine Combined Annotation-Dependent Depletion), a nucleotide-level deleteriousness score for substitutions in Bos taurus and Bos indicus, combining evolutionary constraint, sequence context, epigenetic and regulatory annotations, and gene and protein features. A logistic regression model trained on 41.9 million high-frequency derived alleles from about 3,700 cattle, contrasted with context-matched simulated variants, scored all 8.1 billion possible substitutions. BovCADD distinguished known pathogenic variants from background variation, discriminated among variants within the same consequence class, and scored intronic and intergenic sites. Aggregating scores identified genes carrying rare deleterious variation and revealed elevated genetic load at trait-relevant loci and in bottlenecked, intensively selected populations. Conclusions BovCADD provides the first genome-wide, nucleotide-resolution measure of deleteriousness in cattle, extending variant interpretation to non-coding sequences and linking variant-level prioritization to population-level patterns of mutational burden. Precomputed scores for all substitutions are publicly available.

genomics↗

bioRxiv2026

CellART: a unified framework for extracting single-cell information from high-resolution spatial transcriptomics

Understanding how different cell types assemble into tissues and organs, as well as how they interact to transmit and receive biological signals, is essential for advancing biomedical and biological research. Recent advancements in spatial transcriptomics (ST) technologies have opened new avenues for investigating biological systems by achieving subcellular spatial resolution. Since cells are the fundamental units of life, extracting single-cell information from high-resolution ST data is crucial. However, existing ST platforms often capture sparse transcript counts per spot or measure only a limited number of genes, complicating the extraction of comprehensive single-cell information. In this study, we introduce CellART, a unified framework designed to extract single-cell information across diverse high-resolution ST platforms, including VisiumHD, Xenium, MERFISH, and Stereo-seq. By leveraging multimodal data, such as staining images, spatial transcriptomics data, and single-cell RNA sequencing references, CellART simultaneously performs cell segmentation and cell type annotation through a seamless integration of deep learning and probabilistic modeling. We demonstrate the efficiency, generalizability, and robustness of CellART across various high-resolution spatial transcriptomics platforms, capable of processing datasets containing millions of spots. Comprehensive experiments validate the biological relevance and accuracy of the recovered cellular information within spatial configurations. Notably, we highlight the utility of CellART in breast and colorectal cancer datasets, showcasing its ability to fully leverage high-resolution ST data. By enhancing cellular resolution, CellART facilitates the identification of transient cancer cell states and immune cell subtypes. Furthermore, CellART enables investigations into cancer-immune cell communication, uncovering both established interactions and novel ligand-receptor pairs. The outputs of CellART are compatible with widely used community tools, facilitating a variety of downstream analyses.

bioinformatics↗

bioRxiv2026

Maladaptive Piezo1 Mechanotransduction Drives Smooth Muscle Aging in the Gut

Age-related gastrointestinal dysfunction is common, but the mechanisms of aging-associated smooth muscle failure remain unclear. We show that aging in mice slows whole gut and colonic transit, increases regional stiffness, and reduces smooth muscle contractility. Inducible smooth muscle cell (SMC) specific deletion of Piezo1 preserved youthful transit and force generation, whereas Piezo1 activation in young mice phenocopied aging-associated transit delay. Single cell transcriptomics, RNA velocity, stiffness-controlled cell and tissue cultures, and pharmacologic studies revealed that Piezo1 couples increased stiffness to Ca2+, calcineurin, NFAT signaling, loss of contractile gene programs, leading to age-related contractile loss and contractile to synthetic SMC remodeling and gut wall stiffening. Human intestinal SMCs supported conservation of this pathway, and PIEZO1 gain of function carriers showed a trend toward delayed colonic transit. Thus, maladaptive SMC Piezo1 mechanotransduction is a targetable mechanism of aging-associated gut dysmotility.

physiology↗

bioRxiv2026

Conservation of Nuclear Receptor DAF-12 with Evidence for Ligand Diversification in Plant-Parasitic Nematodes

Plant-parasitic nematodes cause extensive crop losses that threaten global food security and create substantial economic hardship, yet strategies for their control remain limited. Although plant-parasitic nematodes have life cycles that mirror those of their free-living and animal-parasitic relatives, comparatively little is known about the signals that drive life-cycle progression. Dafachronic acids (DAs) are steroid hormones that control life cycle by activating DAF-12 nuclear receptors in Caenorhabditis elegans and animal-parasitic nematodes. To define whether an analogous pathway exists in plant-parasitic nematodes, we investigated the responsiveness of DAF-12 orthologs from six plant-parasitic nematode species to {Delta}7-DA, an endogenous DAF-12 ligand in C. elegans and several animal-parasitic nematodes. We find that whereas some plant-parasitic nematode receptors are activated by {Delta}7-DA, others are not. Structural modeling of all six ligand-binding domains, together with docking of {Delta}7-DA into each model, indicates that responsiveness is governed by a combinatorial ligand-recognition network surrounding the ligand carboxylate rather than by any single contact residue. We further demonstrate that egg and second-stage juvenile extracts from the soybean cyst nematode, Heterodera glycines, lack detectable DA but contain distinct lipophilic fractions that activate its DAF-12 ortholog. Together, these findings suggest that many plant-parasitic nematodes utilize endogenous DAF-12 ligands that are structurally distinct from DA. Uncovering modulators of this pathway could lead to new strategies to combat nematode-driven crop loss.

molecular biology↗