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Frank, M.

Publications and source records attributed to Frank, M..

At least 19 recordsLinked to original sources

LOAM: A family of genomic language models trained on long-read soil metagenomes

Soil ecosystems represent a vast, largely uncharacterised reservoir of microbial diversity. Metagenomic assembly has unlocked access to this resource, and recent advances in long-read sequencing have improved the recovery and quality of microbial genomes from complex samples. While genomic language models have proven highly effective at capturing biological concepts from large sequence datasets, they have predominantly been trained on reference genomes or short-read assemblies. Here, we present LOAM, a family of decoder-only genomic language models ranging from 25 to 624 million parameters and trained exclusively on Oxford Nanopore long-read environmental metagenomes. LOAM model performance scales predictably with model size and training-token budget. Despite a relatively small training sequence corpus, LOAM models outperformed comparably sized models across biological benchmarks, and achieved performance competitive with substantially larger state-of-the-art models trained on much larger datasets. Context-intervention experiments further showed that LOAM models use genomic information over several kilobases, highlighting the potential value of increased contiguity provided by long-read metagenome-assembled genomes. For probe-based benchmark tasks, we systematically evaluated representations across hidden layers and revealed that task-relevant biological information was frequently more linearly accessible from intermediate than final model layers. Finally, we observed that variation in zero-shot variant-effect prediction was strongly associated with the presence of homologous target sequences in the pre-training corpus. Together, these results establish long-read environmental metagenomes as a viable foundation for training competitive genomic language models and demonstrate the importance of both model scale and training-corpus composition for biological generalisation.

genomics↗

Spike and host glycan determinants of HKU1 airway tropism

Human coronavirus HKU1 comprises two distinct serotypes, A and B, whose spike proteins are substantially divergent. Here, we show that spikes from both serotypes preferentially bind 9-O-acetylated 2,8-linked disialosides. Cryo-electron microscopy of the B-type N5 spike reveals a conserved extended binding site in domain S1A that accommodates both the terminal and penultimate sialic acid residues, with interactions involving the penultimate residue substantially enhancing binding. Spike N-glycan processing modulates affinity and linkage selectivity; glycans flanking the binding pocket offer a plausible structural basis for these effects. In contrast to the HKU1-A spike, which adopts open S1B-up conformations upon ligand binding, the N5 apo structure showed that the ligand-binding site was already formed and the e1 relay element register-shifted in most protomers. Nevertheless, we detected neither spontaneous opening nor a transition to an S1B-up state following ligand binding. These findings, obtained with a minimally modified ectodomain, differ from recent reports of ligand-independent opening. Molecular dynamics simulations indicated that membrane-embedded GT3, but not GD3, presents its glycan chain in a geometry compatible with S1A-mediated engagement. Concordantly, in human nasal epithelial cultures cell surface GT3-like O-acetylated trisialoside glycotopes were detected in ciliated cells, linking their cell-type-specific presentation to HKU1 tropism.

microbiology↗

RNAquarium: an archive-scale atlas of zebrafish gene expression coupled with pan-taxonomic profiling reveals diverse viral drivers of transcriptomic states

Zebrafish RNA-seq studies span diverse developmental, physiological, and disease contexts, yet most analyses remain confined to individual experiments and disregard the non-zebrafish component of the data. We present RNAquarium, a scalable framework for joint transcriptomic and metatranscriptomic analysis of RNA-seq data and apply it to all publicly available zebrafish RNA-seq datasets in the Sequence Read Archive. This resource captures transcriptomic structure across development and tissues, reveals diverse microbial and viral associations, and identifies previously undescribed zebrafish viruses including a close relative of human influenza B virus linked to distinct host transcriptional states. We further demonstrate that archive-scale transcriptomes can support foundation-model training and prediction of infection-associated transcriptomic signatures. RNAquarium provides an open framework and interactive portal for exploring the breadth of zebrafish gene expression patterns and associated taxa profiled across a large re-search community and establishes a generalizable strategy for integrating transcriptomic and metatranscriptomic analyses across the diversity of life represented in public sequencing archives.

genomics↗

A multimodal perturbation atlas defines the phenotypic resolution of cellular morphology.

Modeling cellular behavior requires measurements that capture how cells evolve across time, environments, and interventions. Microscopy is uniquely suited to this goal: it is non-destructive and can be applied to living cells in their native context. Yet its phenotypic resolving power remains incompletely characterized relative to molecular assays. Here, we present a multimodal perturbation atlas of 1,000 pooled CRISPR knockouts in A549 cells, profiled by fluorescence microscopy (42 live, 13 fixed markers), label-free quantitative phase imaging of the same live cells (at single timepoints), and single-cell RNA sequencing (scRNA-seq). We develop deep learning frameworks to interpret the rich cell-biological signatures in these ~65M single-cell profiles. At matched reagent cost, phase imaging exceeds the phenotypic resolution of both fluorescence imaging and scRNA-seq, and more reliably recovers higher-order pathway organization. These results establish intrinsic morphology as a high-precision readout of cellular state, and lay a foundation for live-cell profiling of phenotypic trajectories.

systems biology↗

DanioDecima: A DNA sequence-to-function model of zebrafish embryogenesis

Deep learning DNA sequence-to-function models offer the promise of gaining mechanistic insights into genome regulation, however their performance is often limited by data scarcity in the species of interest. We present DanioDecima, a zebrafish-specific model leveraging transfer learning from human and mouse-trained models to predict tissue- and cell-type-specific gene expression during zebrafish embryogenesis. Initializing DanioDecima with pretrained human and mouse Borzoi and Decima weights raises the median pseudobulk Pearson r sub-stantially across cell-types and improves gene-level correlations of test set genes. An in silico directed-evolution loop guided by DanioDecima scoring generated synthetic promoters whose motif architectures cluster by the expected target lineage. These findings exemplify a cross-species transfer learning methodology for sequence-to-function models, and position DanioDecima as a practical resource for zebrafish regulatory engineering.

genomics↗

Specialised root hair cells facilitate rhizobial infection

Legumes establish symbiotic partnerships with soil bacteria that convert atmospheric nitrogen into plant-available forms. Symbiotic bacteria enter through root hairs following recognition by cell surface receptors that help identify compatible symbionts. However, many root hairs express these receptors, and it has long remained unclear why only a small fraction become infected. Here, we use single-cell transcriptomics to show that legumes pre-specify a rare root hair population for infection before bacterial contact. These susceptible root hairs represent less than one percent of the total, express infection-associated genes prior to encountering symbionts and are conserved in distantly related legumes. Their abundance is regulated by the hormone ethylene and correlates with infection capacity. Our findings reveal that root hair cells do not respond uniformly to symbionts but are instead transcriptionally specialised in advance to control infection entry points. This pre-specification provides a mechanism to balance symbiotic benefits against pathogen infection risks and may exemplify a more general strategy used by multicellular hosts to spatially restrict microbial access.

plant biology↗

NLRP3 acts as a direct sensor of intracellular potassium ions

The NLRP3 inflammasome is a sentinel of cellular homeostasis, and its activation triggers the assembly of a molecular machinery that drives inflammation in infection, cardiovascular, metabolic, and neurodegenerative diseases. The majority of the many triggers known to activate NLRP3 are believed to induce potassium ion (K+) efflux from the cell as a fundamental danger signal for compromised cellular integrity. However, it has remained unclear how a reduction in intracellular K+ concentration is mechanistically translated into conformational changes in NLRP3 that promote inflammasome assembly, interleukin (IL)-1 release, and cell death. Here, we provide evidence that alterations in K+ levels directly regulate the conformation of the NLRP3 protein. In cell-free lysates derived from cell lines and primary blood immune cells high K+ concentrations stabilized a compact, protease-resistant structure resembling inhibitor-bound NLRP3, whereas low K+ conditions or the presence of a K+ chelator favored an open, more flexible and protease-accessible conformation. Notably, human NLRP3 remained responsive to K+ even when exogenously expressed in macrophage-like Drosophila cells or purified as recombinant protein. This indicates that K+ sensing occurs independently of cellular co-factors and is consistent with direct ion coordination. Of note, stimulation with the K+-independent NLRP3 agonist CL097 failed to recapitulate the conformational transition caused by K+ efflux inducer, nigericin. Moreover, pathogenic gain-of-function mutant variants of NLRP3 constitutively resembled the open and flexible protease-accessible conformation. Mapping K+-interactions by high-performance computation suggested that K+ ions populate the nucleotide binding pocket of the FISNA-NACHT module of individual NLRP3 chains but also stabilize face-to-face interactions within inactive oligomeric cage assemblies via the NACHT-adjacent acidic loop. Collectively, our findings enable us to propose a mechanistic model of how intracellular K+ ions preclude NLRP3 activation prior to efflux and thus how NLRP3 responds to cellular danger as a direct K+ sensing protein.

immunology↗

Obesity-Driven Lung Lipidome Remodeling Suppresses NK Cell Activation and Antiviral Immunity to Influenza Infection

Obesity is a major risk factor for severe influenza A virus (IAV) infection, however, the innate immune mechanisms underlying this increased vulnerability remain unclear. Here, we identify significant defects in natural killer (NK) cell antiviral responses in mice with diet-induced obesity. In lean mice, NK cells are critical for protection as NK cell depletion during IAV infection led to increased lung viral load, morbidity, and mortality. In contrast, in obese mice NK cell depletion had minimal impact on viral replication or survival. Notably, IAV infection in obese mice recapitulated the phenotype observed in NK cell-depleted lean mice, indicating that obesity is associated with preexisting NK cell dysfunction. Following IAV infection, obese NK cells in the lung were functionally impaired with diminished activation (CD69+), cytokine production (IFN-{gamma}), and cytolytic activity (Granzyme B) accompanied by defects in the mTOR signaling pathway and reduced glycolytic and oxidative metabolism. Bulk and spatial lipidomics revealed obesity and infection-driven remodeling of the lung lipidome. We observed increased triglyceride accumulation, abundance of long-chain free fatty acids, and a shift toward monounsaturated phospholipid species, reshaping the lung microenvironment that coincides with NK cell metabolic dysfunction. Consistent with this lipid-rich environment, obese NK cells sustained high expression of the lipid transporter CD36 post-IAV infection and accumulation of intracellular lipids (LipidTOX+), consistent with mechanisms known to suppress NK cell function. Notably, short-term weight loss (4 weeks) was sufficient to restore NK cell metabolism, antiviral function, and survival following IAV infection. These findings uncover a lipid-associated mechanism regulating NK cell function and show it plays a critical role in defense against infection and that it is dysfunctional in obesity. We suggest that targeting immunometabolism could lead to new antiviral therapies and potentially improve vaccine efficacy, especially in high-risk populations such as obesity. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/710186v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@313263org.highwire.dtl.DTLVardef@1e31111org.highwire.dtl.DTLVardef@758ba6org.highwire.dtl.DTLVardef@12372d0_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Spatial and temporal localization of Serratia ureilytica causing cucurbit yellow vine disease in cucurbits indicates phloem-associated colonization and systemic movement

Cucurbit yellow vine disease (CYVD), caused by the bacterium Serratia ureilytica, is a phloem-associated disease of cucurbits. This study characterized the spatial and temporal distribution of S. ureilytica in Cucurbita pepo cultivar Delicata plants under greenhouse conditions using a GFP-tagged isolate (P01). Seedlings were sampled weekly for four weeks. Transverse sections from the stem, petiole, leaf, shoot apex, and root were imaged by laser scanning confocal and fluorescent dissecting microscopy. In parallel, bacterial abundance in each plant tissue was assessed by quantifying colony-forming units (CFU) via droplet plating over a 4-week time course. Across plant tissues and time points, S. ureilytica fluorescent signal was primarily concentrated in the inner and outer periphery of the bicollateral vascular bundles, with higher magnification images revealing mainly symplastic localization within phloem-associated cells. Consistent with the imaging results, bacterial quantification data showed a high abundance of CFUs in the main stem across weeks, with an irregular pattern of presence in the distal tissues at later time points. These results suggest that S. ureilytica is predominantly localized within phloem-associated cells and spreads both acropetally and basipetally during infection.

plant biology↗

Disentangling blade and vasculature shape in grapevine leaves

The leaf blade and vasculature develop together within a shared morphological space. Despite shared molecular patterning pathways, it is unknown if developmental and evolutionary variation affect these tissues separately or together in a coordinated way. Grapevine leaves have a morphometric history and abundant data measuring the shape of the blade and vasculature together. Using a combination of topological data analysis and deep learning, we perform reciprocal semantic segmentation of leaf blade and vasculature. Each tissue contains sufficient information to predict the other. We hypothesize that this is due to a one-to-one relationship between blade and vein. Using thin plate splines to swap and warp different combinations of blade and vein shapes, we show that a set of leaves with a many-to-one relationship of blade and vein are distinguishable from true leaves. We also swap blade and vein across the developmental series and between species and show that only reversing the developmental series disrupts the relationship between blade and vasculature. We end by discussing the evolutionary and developmental implications that there is a unique, one-to-one mapping between blade and vein that allows each to be predicted from the other. Author summaryLeaves are made of two closely connected parts: the flat blade that captures light and the network of veins that transports water, nutrients, and developmental signals. Although these tissues grow together and share common molecular patterning pathways, it has remained unclear whether a particular blade shape is uniquely linked to a specific vein pattern. In this study, we use grapevine leaves as a model system and combine mathematical shape analysis with deep learning to examine this relationship. We show that the shape of the blade alone can accurately predict the vein network, and that the vein network can likewise predict the blade. This finding suggests a near one-to-one relationship between these two tissues. To test this idea, we created artificial leaves in which blade and vein shapes were deliberately mismatched. Although these synthetic leaves appeared realistic at a global level, a neural network was able to distinguish them from real leaves based on subtle differences. We further show that this tight coupling is maintained by the developmental sequence of leaf growth rather than by species identity, revealing a conserved constraint linking leaf form and internal structure.

plant biology↗

The transcriptional repressor LjTIE1 constrains cytokinin signaling to balance infection and organogenesis during root nodule symbiosis

O_LICytokinin (CK) is a key regulator of root system architecture including primary root (PR) and lateral root (LR) development. During root nodule symbiosis in legumes, CK promotes nodule organogenesis in the root cortex while simultaneously suppressing infection thread (IT) formation in the epidermis, yet the molecular mechanisms enabling this spatial specificity remain incompletely understood. TCP INTERACTOR CONTAINING EAR MOTIF PROTEIN (TIE) proteins negatively regulate CK signaling in Arabidopsis roots, but whether legume orthologs modulate symbiotic CK responses remains unknown. C_LIO_LIWe characterized Lotus tie1 loss-of-function mutants through root and nodulation assays, transcriptomics, confocal microscopy of CK signaling reporter TCSn, and ethylene quantification. C_LIO_LILjTIE1 expression was induced by CK and Nod-factor, tie1 mutants exhibited reduced PR length, LR density, IT formation, and nodule number alongside elevated ethylene emission - phenotypes fully rescued by ethylene biosynthesis inhibition. Despite enhanced CK signaling (confirmed via TCSn reporter and transcriptomics), tie1 roots formed no spontaneous nodules but displayed hypernodulation under exogenous CK treatment. C_LIO_LILjTIE1 provides temporal control of symbiosis by dampening CK signaling after nodule initiation, revealing a regulatory layer that prevents constitutive nodulation despite elevated CK perception. C_LI

plant biology↗

Achieving Micrometer-Scale 4D X-ray tomography of Living Leaf Tissue in the Laboratory

A methodology for achieving micrometer-scale 4D X-ray lab microscopy of living leaf tissue was developed to overcome challenges associated with delicate tissues, radiation damage, and motion artifacts during in vivo imaging. The study focused on optimizing laboratory based X-ray micro-computed tomography (microCT) parameters to balance high-resolution imaging with minimized physiological stress and radiation dose quantification. Assessing the dose-safe imaging window required comparing vertical and horizontal leaf mounting setups. Results demonstrated that the horizontal setup provided greater stability, preventing tissue degradation and maintaining sample viability during continuous acquisitions lasting up to 22 hours ([~]15600 Gy). MicroCT capacities were clearly able to resolve microstructures at the cellular level, achieving a pixel size down to 1 {micro}m. Furthermore, this optimized methodology confirmed the ability to track the spatiotemporal dynamics of applied compounds such as iohexol and aggregated nanoparticles within the leaf tissue. This work establishes that accessible laboratory based microCT enables the in vivo 4D monitoring of anatomical and physiological changes in living plants.

plant biology↗

Optimal Cannabinoid-Terpene Combination Ratios Suppress Mutagenicity of Gastric Reflux in Normal and Metaplastic Esophageal Cells

BackgroundEsophageal adenocarcinoma (EAC) frequently arises from chronic exposure to acid and bile reflux, with secondary bile acids, such as deoxycholic acid (DCA), contributing to its pathogenesis through mechanisms involving reactive oxygen species (ROS), oxidative DNA damage, and resistance to apoptosis. The human endocannabinoid system (ECS) regulates diverse anti-inflammatory, antioxidant, and analgesic pathways implicated in disease modulation. Despite its therapeutic promise, effective pharmacological activation of the ECS remains challenging. ObjectivesThis study aimed to evaluate whether specific cannabinoid-terpene combinations targeting the ECS could attenuate the mutagenic and cytotoxic effects of bile acid-induced stress in esophageal cell models. Additionally, we assessed the clinical significance of ECS-related protein receptors in the progression of EAC. DesignIn vitro experimental models combined with clinical samples analyses. MethodsWe utilized in vitro models, including human esophageal epithelial cell lines exposed to DCA and a Barretts esophagus gastroesophageal reflux (GER) model subjected to low pH and a bile acid cocktail. Patient-derived samples were analyzed to investigate the clinical association of ECS pathway markers with EAC progression. Experimental models were treated with varying ratios of phyto-cannabinoids and terpenes. Endpoints included assessment of DNA damage, mitochondrial membrane potential, and ROS production to identify optimal compound combinations. Expression of ECS-related protein receptors was evaluated in clinical samples to elucidate their role in EAC development. ResultsA 1:5 ratio of cannabigerol (CBG) to Phytol (Phy) was found to significantly reduce DCA-induced DNA damage, preserve mitochondrial membrane potential, and decrease ROS levels. This combination also enhanced apoptosis in damaged cells and diminished mutagenicity. Analysis of patient samples revealed that the expression of the ECS-associated receptor protein CB1 correlated with EAC progression, suggesting a broader clinical role for ECS modulation in cancer prevention. ConclusionModulation of the ECS through carefully selected cannabinoid-terpene ratios can mitigate bile acid-induced esophageal damage and may reduce carcinogenic progression. These findings support further in vivo investigations and raise the possibility of expanding cannabinoid-terpene therapeutics to other conditions involving similar pathogenic processes.

cancer biology↗

Characterizing a hallmark of glymphatic insufficiency: Wasteosomes accumulate in periventricular white matter hyperintensities and exhibit complex relationships with mixed pathology, sclerotic index and perivascular space

The glymphatic system is a recently elucidated waste clearance system in the brain, thought to be critical for the maintenance of homeostasis. Corpora amylacea or "wasteosomes", are discontinuous lipid labyrinth structures that are polyglucosan rich, retain cellular waste and are thought to be of astrocytic origin. Wasteosomes have been proposed as a hallmark of glymphatic insufficiency predominantly due to: 1) their spatial localization around glymphatic drainage points including periventricular (PV) regions, perivascular spaces (PVS), and sub-pial regions; and, 2) their correlation with aging, vascular disorders, neurodegenerative diseases, and conditions that impair sleep. White matter hyperintensities (WMHs) are diffuse hyperintense areas seen on T2-weighted or fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) scans that represent damage to white matter. PV WMHs and are known predictors of mild cognitive impairment, stroke, dementia and death. The relationship between wasteosome accumulation, PV WMHs, vascular pathology and PVS is currently unknown. For the first time, in a mixed diagnostic cohort of pathologically diagnosed: Alzheimers disease (AD), cerebrovascular disease (CVD), mixed AD/CVD, and control tissue with no pathological diagnosis, we connected the histopathological wasteosome profile in periventricular brain sections in relation to 7T FLAIR-MRI confirmed PV WMHs, vascular stenosis and PVS. Our results reveal wasteosomes accumulate in PV WMHs, are increased in proximity to large PV venules, and exhibit complex relationships with WMH severity, mixed pathology, sclerotic index and PVS. These findings suggest wasteosomes may serve as histological markers of impaired glymphatic drainage and provide new insights into the pathophysiology underlying white matter injury.

neuroscience↗

Novel polymer fixed-target microfluidic platforms with an ultra-thin moisture barrier for serial macromolecular crystallography

The advent of ultrabright fourth generation X-ray light sources, including X-ray free-electron lasers (XFELs) and diffraction limited synchrotrons, has significantly advanced the field of serial macromolecular protein crystallography (SX). SX experiments demand a continuous supply of fresh microcrystalline sample, ideally while minimizing overall sample consumption. Here, we introduce a novel, robust, and user-friendly polymer film technology that can be assembled in various configurations to encapsulate protein microcrystals and provide sample support for SX. This system provides an efficient hydration barrier over extended durations while maintaining an exceptionally low X-ray background. We have validated this technology by assessing hydration retention under both ambient and ultra-high vacuum conditions, and by evaluating its mechanical stability under XFEL pulses. Furthermore, we have demonstrated the effectiveness of this approach in two room-temperature serial crystallography studies to determine the structure of a 24 kDa Rapid Encystment Phenotype (REP24) protein from Franciscella tularensis.

biophysics↗

Redesigning petal shape, size, and color in soybean reveals unexpected phenotypes for floral organ development

Soybean (Glycine max) has not yet benefited from large-scale hybrid breeding efforts due to its small, self-fertilizing flowers that are difficult to emasculate, and limited attractiveness to pollinators. This study explores targeted floral trait engineering to enhance pollinator attraction, aiming to overcome barriers to soybean hybridization. We generated a high-resolution floral organ expression atlas and H3K4 trimethylation ChIP-Seq dataset to identify candidate genes involved in petal development, nectar sugar content, and petal pigmentation. Using CRISPR-based activation and repression systems, we modified the expression of AINTEGUMENTA (GmANT), BIGPETAL (GmBPE), and SUCROSE TRANSPORTER2 (GmSUC2). Contrary to expectations based on Arabidopsis homologs, transcriptional activation of GmANT_B and repression of GmBPE led to reduced, rather than increased, petal size, highlighting divergent regulatory mechanisms in soybean. Complementation of the W1 gene that controls petal pigmentation successfully converted white petals to purple, with preliminary evidence indicating that this color conversion may increase pollinator visitation. These results underscore the complexity of floral development in soybean and provide foundational tools and resources for future efforts to engineer reproductive traits for hybrid seed production.

plant biology↗

Probing the Role of Membrane in Neutralizing Activity of Antibodies Against Influenza Virus

Influenza poses a major health issue globally. Neutralizing antibodies targeting the highly conserved stem region of hemagglutinin (HA) of the influenza virus provide considerable protection against the infection. Using an array of advanced simulation technologies, we developed a high-resolution structural model of full-length, Fab-bound HA in a native viral membrane to characterize direct membrane interactions that govern the efficacy of the antibody. We reveal functionally important residues beyond the antibodys complementary-determining regions that contribute to its membrane binding. Mutagenesis experiments and infectivity assays confirm that deactivating the membrane-binding residues of the antibody decreases its neutralization activity. Therefore, we propose that the association with the viral membrane plays a key role in the neutralization activity of these antibodies. Given the rapid evolution of the influenza virus, the developed model provides a structural framework for the rational design and development of more effective therapeutic antibodies.

biophysics↗

A unified framework for hydromechanical signaling: Do plant signals go with the flow?

Local wounding in plants triggers signals that travel locally within the wounded leaf or systemically through the vasculature to distal leaves. The transmission mechanisms of this ubiquitous class of signals remain poorly understood. Here, we develop a unifying framework based on poroelastic dynamics to study two coupled biophysical processes - propagation of pressure changes and transmission of chemical elicitors via mass flows driven by these pressure changes - as potential mechanisms for the initiation and propagation of wound-induced signals. We show that rapid pressure changes in the xylem can transmit mechanical information across the plant, while their coupling with neighboring non-vascular tissue drives swelling and mass flow that can transport chemical elicitors to distal leaves. We confront our model predictions with signaling dynamics measurements in several species, and show that the poroelastic model captures observed mechanical, biochemical, and electrophysiological signals. This framework provides a valuable foundation for assessing mechanisms of signal transmission and for designing future experiments to elucidate factors involved in signal initiation, propagation, and target elicitation.

plant biology↗