Biology subjects

Ryu, H.

Publications and source records attributed to Ryu, H..

At least 19 recordsLinked to original sources

bioRxiv2026

Hyperactivation of the AXL-ICD/SIRT2 axis by Amyloid-β impairs astrocytic autophagic flux and exacerbates neuroinflammation

Autophagy dysfunction and neuroinflammation are central to Alzheimer's disease (AD), yet how extracellular amyloid-{beta} (A{beta}) couples to impaired autophagic flux and heightened neuroinflammation remains unknown. Here, we identify the TAM receptor AXL as a molecular transducer that couples A{beta} sensing to the regulation of autophagy and neuroinflammation in astrocytes. A{beta} induces {gamma}-secretase-dependent cleavage of AXL, generating a nuclear intracellular domain (AXL-ICD) that forms phase-separated condensates and activates autophagy gene transcription through SIRT2-mediated recruitment of the RUVBL1/2-INO80 chromatin-remodeling complex. This axis is activated in astrocytes of postmortem AD brains. Concurrently, AXL-ICD binds to the SIRT2 catalytic domain and suppresses its deacetylase activity, increasing -tubulin acetylation and altering microtubule dynamics. While moderate AXL-ICD levels promote autophagic flux, excessive elevation paradoxically triggers microtubule hyperstabilization, thereby impairing autophagosome-lysosome fusion and causing pathological accumulation of autophagosomes and H2O2. The inhibitory peptide AxSBiP disrupts the AXL-ICD/SIRT2 interaction, restores autophagic flux, reduces plaque burden, and normalizes A{beta}-induced H2O2 production and astrogliosis in APP/PS1 mice. We propose the AXL-ICD/SIRT2 axis as an effective therapeutic target to reduce A{beta} burden and neuroinflammation in AD

neuroscience↗

bioRxiv2026

The anatomical compartment defines distinct immune remodeling within human visceral adipose tissue during aging

Age-associated inflammation varies across tissues, but whether distinct visceral adipose tissue (VAT) depots undergo inflammatory remodeling in a depot-specific manner remains unclear. Here we profiled human peri-organ VAT, comparing kidney-associated fat (KF, from kidney transplantation donors) and gallbladder-associated fat (GBF, from asymptomatic cholecystectomy patients with incidental polyps), using single-cell RNA sequencing, flow cytometry, intracellular protein profiling and in situ analysis. GBF showed broad tissue-residency and granzyme K-associated remodeling across conventional, regulatory and innate-like lymphocyte compartments, whereas KF showed stronger B cell remodeling, greater myeloid representation and more compartmentalized changes within resident effector-like CD8+ T cell states. We further identified age-associated CD20+ T cells with features consistent with local B-T cell interaction and an antigen-experienced, granzyme K-associated inflammatory memory phenotype. In situ analysis revealed age-associated myeloid accumulation and crown-like structure remodeling, accompanied by distinct myeloid inflammatory programs in KF and GBF. Finally, depot-specific immune signatures associated with clinical indices of adjacent kidney and liver function. These findings indicate that age-associated distinct immune programs within peri-organ VAT depots track with local tissue context and the state of the adjacent organ.

immunology↗

bioRxiv2026

Estimating the fraction of variance of crystallized intelligence explained by cortical surface area in early adolescence

The relationship between cortical morphology and intelligence during adolescence has been widely studied, with existing literature reporting varying degrees of association across different modeling approaches. This study provides a comprehensive comparison of model performance in investigating the association between crystallized intelligence and cortical surface area using data from 11,351 subjects in the Adolescent Brain Cognitive Development (ABCD) study. We evaluate ten widely used models ranging from linear regression to graph convolutional networks across three covariate adjustment formulations: full (no adjustment), partial (age and sex adjusted), and total surface area (TSA) partial (age, sex, and TSA adjusted). Using bootstrap resampling with 50 iterations, we estimate the fraction of variance explained (FVE) for each model. Our results suggest that more complex models do not lead to higher FVE, with LASSO having the highest FVE of 15.9% (full formulation), Ridge at 10.5% (partial formulation), and Principal Component Regression (PCR) with 102 PCs at 2.5% (TSA partial formulation). Our results also reveal that the relationship between cortical surface area and crystallized intelligence is predominantly driven by global factors age, sex, and TSA, rather than by localized cortical surface area.

neuroscience↗

bioRxiv2026

A novel fracture lattice in spiny mouse skin facilitates tissue autotomy and regeneration

Autotomy is a unique phenotype whereby an animal sheds a body part to escape predation1-3. The timing and location of autotomy are tightly regulated by preformed planes of weakness (aka fracture planes) which facilitate tissue loss. While autotomy is often followed by regeneration, these phenotypes are rarely reported in mammals4-9. A notable exception are spiny mice (Acomys) which exhibit skin autotomy and more remarkably, complete tissue regeneration10-14. Presently, mechanisms underlying autotomy and complete regeneration in Acomys skin remain elusive. Here, we report the discovery of a honeycomb-like fracture lattice in Acomys skin whose design directs tissue destruction but also facilitates regenerative healing. Unlike the single continuous surface of a fracture plane, this fracture lattice consists of a three-dimensional array of hexagonal units whose boundaries guide tissue breakage. Moreover, we identify collagen VI as the main constituent of the fracture lattice and find that it is distinctly arranged to initiate fracturing and propagation of skin tearing. By preconditioning the tissue for autotomy, the fracture lattice dampens the damage-induced inflammatory response but also upregulates a pro-regenerative gene signature, accelerating skin appendage regeneration. Lastly, we discovered the key role of spiny hairs in fracture lattice formation, as inhibiting their development leads to abnormal pattern formation and changes in skin fracture mechanics. Our results present a novel example of a uniquely evolved structural adaptation in mammalian skin that links tissue patterning, autotomy and regeneration. We expect that the application of a modular compartment structure to artificial skin and other organ engineering may enhance resilience to injury and facilitate efficient regeneration.

developmental biology↗

bioRxiv2026

Pharmacological intervention targeting neuroimmune axis in the aging hypothalamus prevents age-associated physiological decline

Systemic physiological aging is largely driven by disrupted metabolic homeostasis, yet the central mechanisms of this metabolic dysfunction remain poorly defined. Here, we identify the hypothalamus as a critical hub driving systemic aging through neuroimmune-mediated mechanisms. Single-cell transcriptomic and immunohistochemical analyses revealed that aged hypothalami exhibit significant infiltration of CD8 T lymphocytes, beginning in middle age, with signatures of activation and tissue residency. These T cells intimately interact with tanycytes and microglia, promoting neuroinflammation and progressive tanycyte loss, a defining hallmark of hypothalamic aging. T cell receptor profiling revealed a substantial presence of invariant natural killer T (iNKT) and mucosal-associated invariant T (MAIT) cells, likely activated through cytokine-driven, antigen-independent mechanisms. In aged hypothalamus, microglia secrete chemokines CCL3 and CCL4, whose ectopic expression in young mice was sufficient to trigger persistent hypothalamic T cell infiltration and accelerated systemic aging. Circulating oxidized LDLs (OxLDLs) were identified as upstream inducers of this chemokine response. Notably, pharmacological blockade of the CCL3/4-CCR5 axis with Maraviroc and Cenicriviroc prevented T cell recruitment and ameliorated metabolic and physiological impairments. Given the clinical safety of CCR5 antagonists and individuals lacking functional CCR5 remain generally healthy throughout life, our findings highlight midlife CCL3/4-CCR5 inhibition as a translatable therapeutic target for delaying age-related decline and promoting healthspan.

neuroscience↗

bioRxiv2025

Structural basis of cyclic phytocytokine recognition by the HSL3/NUT receptor

Plant receptor kinases perceive diverse peptide signals to coordinate stress responses and developmental programs. The HAESA-LIKE 3 (HSL3/NUT) receptor recognizes CTNIP/SCREW phytocytokines--disulfide-stabilized cyclic peptides that regulate immune signaling and stress adaptation. However, how HSL3 distinguishes these structurally constrained cyclic peptides from linear signaling molecules remains unknown. Here we report near-atomic resolution cryo-EM structures of HSL3 in apo and CTNIP448-70-bound states at [~]2.6 [A], using Arabidopsis CTNIP4 as a representative family member, revealing distinct mechanisms for cyclic peptide recognition. The conserved CTNIP motif occupies a negatively charged pocket in HSL3s C-terminal region through a combination of polar contacts, hydrogen bonds, salt bridges, and van der Waals interactions. The receptor employs a two-step recognition mechanism--electrostatic steering followed by motif anchoring--that enables rapid ligand capture and release, consistent with the transient nature of stress signaling. Notably, an N-glycan at Asn449 directly contacts the CTNIP4 peptide, establishing glycosylation as an active participant in ligand recognition. Structure-guided mutagenesis combined with reactive oxygen species (ROS) burst assays confirmed the functional importance of key binding interfaces. N-terminal truncation experiments revealed a minimal active fragment: CTNIP451-70 supported both rapid ROS production and sustained seedling growth inhibition, whereas the shorter CTNIP454-70 variant retained ROS activity but failed to trigger long-term seedling growth inhibition. Structure-guided coevolutionary analysis across plant lineages reveals patterns of both conserved and variable receptor-ligand interfaces, highlighting evolutionary flexibility while preserving core features of recognition. These conserved recognition principles, mediated by receptor glycosylation and evolutionary plasticity, enable specificity in peptide signaling with implications for engineering stress-resilient crops.

plant biology↗

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

Immune Cell Dysfunction of SARS-CoV-2: Mathematical Modeling of the Within-Host Immune Dynamics

The COVID-19 pandemic has spurred extensive research into viral transmission and control, yet the mechanisms of the human immune response to SARS-CoV-2 remain incompletely understood, particularly the role of natural killer (NK) cells and cytokine regulation in disease severity. Mathematical modeling provides a powerful approach to bridge this gap by linking viral dynamics with immune interactions. In this work, we develop a mechanistic within-host model, formulated in a system of coupled ordinary and delayed differential equations, to investigate the contributions of NK cell activity, interferon signaling, and pro-inflammatory cytokines to viral clearance and disease outcome. Model parameters are estimated from experimental data, and computational simulations are used to explore how dysregulated NK responses and cytokine feedback loops may drive divergent clinical outcomes. Local sensitivity analysis identifies the most influential parameters shaping host-pathogen dynamics, highlighting potential control points for intervention. In addition, knockdown simulations are performed to mimic potential therapeutic interventions, allowing us to evaluate their advantages and limitations in silico. These findings provide mechanistic insights into COVID-19 immune dynamics and offer a foundation for guiding the design of future treatment strategies. HighlightsO_LIWe develop a within-host mathematical model of the SARS-CoV-2 immune response. C_LIO_LIThe model incorporates key cytokines and immune cells including Natural Killer cells. C_LIO_LINumerical simulations reproduce cytokine storms and NK cell dysfunction in severe disease. C_LIO_LISensitivity analysis identifies parameter impact and potential therapeutic interventions. C_LI

immunology↗

bioRxiv2025

Modeling Bistable Dynamics Arising from Macrophage-Tumor Interactions in the Tumor Microenvironment

Macrophages in the tumor microenvironment (TME), known as tumor-associated macrophages (TAMs), originate primarily from circulating monocytes that differentiate under the influence of tumor-derived signals. Within the TME, naive macrophages can adopt either a pro-inflammatory, anti-tumor (M1-like) or anti-inflammatory, pro-tumor (M2-like) phenotype. These pheno-typic shifts significantly affect tumor progression, making TAMs attractive targets for therapeutic intervention aimed at blocking recruitment, promoting anti-tumor polarization, or disrupting tumor-macrophage interactions. In this study, we develop a mathematical model capturing the temporal dynamics of tumor volume alongside populations of naive, M1-like, M2-like, and mixed (M1/M2) phenotype TAMs. The model incorporates the bidirectional influence between tumor development and macrophage polarization. We conduct the bifurcation as well as global sensitivity analyses to identify regions of bistability for tumor dynamics in the parameter space and the impact of sensitive parameters on TME. The model results are then linked to treatment strategies that may effectively induce transitions from high to low tumor burden. HighlightsO_LIWe propose a mathematical model to describe the temporal evolution of the tumor volume alongside different phenotypes of tumor-associated macrophages (TAMs). C_LIO_LIWe investigate the impact of TAMs on tumor growth and decline as well as the influence of the tumor on transition rates between different TAM phenotypes. C_LIO_LIBifurcation and global sensitivity analyses reveal the regions of bistability for tumor dynamics and the impact of sensitive model parameters on the tumor microenvironment. C_LIO_LIModel results are linked to treatment strategies that manipulate the bistable system to transition from high to low tumor volume. C_LI

systems biology↗

bioRxiv2025

Identification of reactive CpGs and RNA expression in early COVID-19 through cis-eQTM analysis reflecting disease severity and recovery

Multi-omics analyses of severe COVID-19 cases are crucial in deciphering the complex interplay between genetic and epigenetic factors. Here, we present an analysis of Expression Quantitative Trait Methylation (eQTM) to investigate the complex interplay of methylation and gene expression pattern during the acute phase of severe COVID-19. We identified 16 differentially expressed genes and 30 nearby differentially methylated CpG sites. Six key genes--SRXN1, FURIN, IL18RAP, FOXO3, GCNT4, and FKBP5--were either up-regulated or down-regulated near hypomethylated CpG sites. These genes are associated with viral infiltration, immune activation, lung damage, and oxidative stress-related multi-organ failure, which are the hallmarks of severe COVID-19. Interestingly, during the recovery phase, methylation and gene expression levels returned to baseline, underscoring the rapid and reversible nature of these molecular changes. These findings provide insight into the dynamics of epigenetic and transcriptomic shifts according to the infectious stage, supporting potential prognostic and therapeutic approaches for severe COVID-19.

bioinformatics↗

bioRxiv2024

Reversible Transcriptomic Age Shifts from Physiological Stress in Whole Blood

We developed a genome-wide transcriptomic clock for predicting chronological age using whole blood samples from 463 healthy individuals. Our findings reveal profound age acceleration, up to 24.47 years, under perturbed homeostasis in COVID-19 patients, which reverted to baseline upon recovery. This study demonstrates that the whole blood transcriptome can track reversible changes in biological age induced by stressors in real physiological time, suggesting a potential role for anti-aging interventions in disease management.

bioinformatics↗

bioRxiv2024

Loss of MEF2C function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice

Genetic changes and epigenetic modifications are associated with neuronal dysfunction in the pathogenesis of neurodegenerative disorders. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear. Here, we identified an ALS-associated SNP located in the intronic region of MEF2C (rs304152), residing in a putative enhancer element, using convolutional neural network. The enhancer mutation of MEF2C reduces own gene expression and consequently impairs mitochondrial function in motor neurons. MEF2C localizes and binds to the mitochondria DNA, and directly modulates mitochondria-encoded gene expression. CRISPR/Cas-9-induced mutation of the MEF2C enhancer decreases expression of mitochondria-encoded genes. Moreover, MEF2C mutant cells show reduction of mitochondrial membrane potential, ATP level but elevation of oxidative stress. MEF2C deficiency in the upper and lower motor neurons of mice impairs mitochondria-encoded genes, and leads to mitochondrial metabolic disruption and progressive motor behavioral deficits. Together, MEF2C dysregulation by the enhancer mutation leads to mitochondrial dysfunction and oxidative stress, which are prevalent features in motor neuronal damage and ALS pathogenesis. This genetic and epigenetic crosstalk mechanism provides insights for advancing our understanding of motor neuron disease and developing effective treatments.

neuroscience↗

bioRxiv2024

Tissue Regeneration Requires Edema Fluid Clearance by Compensatory Lymphangiogenesis in Zebrafish

Lymphangiogenesis is essential for tissue regeneration and edema clearance, and delayed or failed lymphangiogenesis is a critical cause of impaired healing. However, elucidating the dynamic changes in lymphangiogenesis during tissue regeneration in animal models in real-time has been challenging; thus, the mechanisms of compensatory lymphatic activation for edema clearance remain unclear. To address this, zebrafish were subjected to osmotic stress using a hypertonic solution (375 mOsm/L) and hypotonic solution (37.5 mOsm/L) to induce tissue damage followed by edema formation. Intravital imaging of Tg(mrc1a:egfp; kdrl:mcherry) larvae unveiled substantial lymphatic vessel remodeling during tissue regeneration. The increase of lymphatic endothelial progenitor cells accompanied by sustained expansion and remodeling of primary lymphatics during recovery suggested active lymphangiogenesis during tissue repair. We developed a novel method using translating ribosome affinity purification to scrutinize the translatome of lymphatic endothelial cells in vivo. This analysis revealed the upregulation of key pro-lymphangiogenic genes, notably vegfr2 and vegfr3, during tissue regeneration. Pharmacological inhibition of these Vegfr2/Vegfr3 prevented compensatory lymphangiogenesis and impaired healing. Our findings provide a new model of in vivo live imaging of regenerative lymphangiogenesis, presenting a novel approach to investigating lymphatic activation during tissue regeneration.

developmental biology↗

bioRxiv2024

Identification of 17 novel epigenetic biomarkers associated with anxiety disorders using differential methylation analysis followed by machine learning-based validation

BackgroundThe changes in DNA methylation patterns may reflect both physical and mental well-being, the latter being a relatively unexplored avenue in terms of clinical utility for psychiatric disorders. In this study, our objective was to identify the methylation-based biomarkers for anxiety disorders and subsequently validate their reliability. MethodsA comparative differential methylation analysis was performed on whole blood samples from 94 anxiety disorder patients and 296 control samples using targeted bisulfite sequencing. Subsequent validation of identified biomarkers employed an artificial intelligence- based risk prediction models: a linear calculation-based methylation risk score model and two tree-based machine learning models: Random Forest and XGBoost. Results17 novel epigenetic methylation biomarkers were identified to be associated with anxiety disorders. These biomarkers were predominantly localized near CpG islands, and they were associated with two distinct biological processes: 1) cell apoptosis and mitochondrial dysfunction and 2) the regulation of neurosignaling. We further developed a robust diagnostic risk prediction system to classify anxiety disorders from healthy controls using the 17 biomarkers. Machine learning validation confirmed the robustness of our biomarker set, with XGBoost as the best-performing algorithm, an area under the curve of 0.876. ConclusionOur findings support the potential of blood liquid biopsy in enhancing the clinical utility of anxiety disorder diagnostics. This unique set of epigenetic biomarkers holds the potential for early diagnosis, prediction of treatment efficacy, continuous monitoring, health screening, and the delivery of personalized therapeutic interventions for individuals affected by anxiety disorders.

bioinformatics↗

bioRxiv2024

Astrocytic hemoglobin is an H2O2-decomposing peroxidase and therapeutic target for Alzheimer's disease

Summary paragraphHemoglobin (Hb) is well-known for transporting oxygen in red blood cells within blood vessels1. Although Hb is also present in the brain2, its role remains poorly understood. Here, we show that Hb, found in astrocytes of neurodegenerative animal models and patients, displays significant antioxidant effects through its H2O2-decomposing peroxidase activity, and a small molecule enhancer boosts this activity, reducing aberrant H2O2 and mitigating H2O2-induced neurodegeneration. To counteract the harmful effects of aberrant H2O2-production in Alzheimers disease (AD), we developed KDS12025, a blood-brain barrier (BBB)-permeable small molecule that effectively enhances the peroxidase activity of Hb by a hundredfold, especially at a low level of Hb. KDS12025 and its analogs achieve this enhancement through its electron-donating amine group. KDS12025 reduces H2O2 levels in astrocytes, exhibits neuroprotective effects, and reverses memory impairment in AD models. Gene-silencing of Hb{beta} abrogates KDS12025s impact in both culture and animal models of AD. Moreover, KDS12025 prevented the death of dopaminergic neurons in a Parkinsons disease (PD) model without altering the oxygen-transporting function of Hb. KDS12025 extended survival and improved motor function even in the severe amyotrophic lateral sclerosis (ALS) mouse model. Our findings propose Hb as a new therapeutic target for neurodegenerative diseases, with KDS12025 emerging as a first-in-class drug candidate that enhances Hbs peroxidase activity to reduce H2O2. Boosting Hbs peroxidase activity with KDS12025 mitigates oxidative stress and alleviates neurodegeneration in AD, PD, and ALS with broad applicability for numerous oxidative-stress-driven diseases.

neuroscience↗

bioRxiv2024

Cell Simulation as Cell Segmentation

Single-cell spatial transcriptomics promises a highly detailed view of a cells transcriptional state and microenvironment, yet inaccurate cell segmentation can render this data murky by misattributing large numbers of transcripts to nearby cells or conjuring nonexistent cells. We adopt methods from ab initio cell simulation to rapidly infer morphologically plausible cell boundaries that preserve cell type heterogeneity. Benchmarking applied to datasets generated by three commercial platforms show superior performance and computational efficiency of this approach compared with existing methods. We show that improved accuracy in cell segmentation aids greatly in detection of difficult to accurately segment tumor infiltrating immune cells such as neutrophils and T cells. Lastly, through improvements in our ability to delineate subsets of tumor infiltrating T cells, we show that CXCL13-expressing CD8+ T cells tend to be more closely associated with tumor cells than their CXCL13-negative counterparts in data generated from renal cell carcinoma patient samples.

bioinformatics↗

bioRxiv2024

The sperm hook in house mice: a functional adaptation for migration and self-organised behaviour

In most murine species, spermatozoa exhibit a falciform apical hook at the head end. The function of the sperm hook is not yet clearly understood. In this study, we investigate the role of the sperm hook in the migration of spermatozoa through the female reproductive tract in Mus musculus (C57BL/6), using a deep tissue imaging custom-built two-photon microscope. Through live reproductive tract imaging, we found evidence indicating that the sperm hook aids in the attachment of spermatozoa to the epithelium and facilitates interactions between spermatozoa and the epithelium during migration in the uterus and oviduct. We also observed synchronised sperm beating, which resulted from the spontaneous unidirectional rearrangement of spermatozoa in the uterus. Based on live imaging of spermatozoa-epithelium interaction dynamics, we propose that the sperm hook plays a crucial role in successful migration through the female reproductive tract by providing anchor-like mechanical support and facilitating interactions between spermatozoa and the female reproductive tract in the house mouse.

cell biology↗

bioRxiv2024

Candidatus Nitrosocosmicus members are the dominant archaea associated with pepper (Capsicum annuum L.) and ginseng (Panax ginseng C.A. Mey.) plants rhizospheres

BackgroundAlthough archaea are widespread in terrestrial environments, little is known about the selection forces that shape their composition, functions, survival, and proliferation strategies in the rhizosphere. The ammonia-oxidizing archaea (AOA), which are abundant in soil environments, catalyze the first step of nitrification and have the potential to influence plant growth and development significantly. ResultsBased on archaeal 16S rRNA and amoA gene (encoding the ammonia monooxygenase subunit A) amplicon sequencing analysis, distinct archaeal communities dominated by AOA were found to be associated with the root systems of pepper (Capsicum annuum L.) and ginseng (Panax ginseng C.A. Mey.) plants compared to bulk soil not penetrated by roots. AOA related to "Candidatus Nitrosocosmicus", which, unlike most other AOA, harbor genes encoding manganese catalase (MnKat), dominated rhizosphere soils, and thus contributed to the development of distinct archaeal communities in rhizospheres. Accordingly, for both plant species, the copy number ratios of AOA MnKat genes to amoA genes were significantly higher in rhizosphere soils than in bulk soils. In contrast to MnKat-negative strains from other AOA clades, the catalase activity of a representative isolate of "Ca. Nitrosocosmicus" was demonstrated. Members of this clade were enriched in H2O2-amended bulk soils, and constitutive expression of their MnKat gene was observed in both bulk and rhizosphere soils. ConclusionsDue to their abundance, "Ca. Nitrosocosmicus" members can be considered key players mediating the nitrification process in rhizospheres. The selection of this MnKat-containing AOA in rhizospheres of several agriculturally important plants hints at a previously overlooked AOA-plant interaction. For additional mechanistic analyses of the interaction, this key clade of AOA with cultured representatives can be employed.

microbiology↗