Biology subjects

Roy, A.

Publications and source records attributed to Roy, A..

At least 19 recordsLinked to original sources

bioRxiv2026

TRACEDD: A Tool-grounded Reasoning and Agentic Coordination for Explainable Drug Design

Drug discovery depends on coordinated decisions across target validation, structure analysis, molecular design, developability assessment and synthetic feasibility, but current computational methods often operate as disconnected tools. Here, we introduce TRACEDD (Tool-grounded Reasoning and Agentic Coordination for Explainable Drug Design), a framework that makes three primary contributions: (1) It establishes a 'tool-first' multi agentic architecture where LLMs orchestrate validated computational tools rather than replace them, ensuring scientific rigor. (2) It implements a multi-agent system that mirrors expert discovery teams, enabling transparent and traceable decision-making through a Reason-Act-Observe loop. (3) It demonstrates an end-to-end workflow, from target validation to synthesis planning, that adaptively handles real-world data variability, such as the absence of experimental structures. The framework decomposes discovery into specialized agents for target validation, druggability assessment, molecular generation, lead optimization, ADMET evaluation, literature evidence integration and retrosynthesis, all operating through a Reason Act Observe workflow. Using JAK2 as a representative case, we show that the system can retrieve experimental protein structures, invoke AlphaFold when structures are unavailable, identify druggable pockets and perform de novo molecular generation. Known JAK2 inhibitors are used to define design hypotheses and guide reinforcement learning-based molecular generation, with docking scores/predicted pIC50 and other physicochemical/ADMET properties serving as reward and prioritization signals. The framework demonstrates a tool-first, reasoning-driven approach in which each major decision is linked to explicit tool invocation, intermediate evidence. By combining agentic orchestration with domain-specific computational tools, the system supports transparent, adaptable and human-verifiable molecular design workflows, providing a foundation for more reliable AI-assisted drug discovery.

bioinformatics↗

bioRxiv2026

Keratinizing Squamous and Intestinal Metaplasia in Urothelium of Long-term Catheterized Patients with Chronic Urinary Tract Infections

Purpose: Many spinal cord-injured (SCI) patients are recurrently catheterized to manage urinary retention and incontinence. Microbial pathogens colonize urethral catheter surfaces, persist in form of biofilms and trigger inflammatory responses in the bladder. Our objective was to determine bladder tissue changes due to long-term inflammation using LC-MS proteomics. Experimental Design: We examined longitudinal proteomic profiles from eight SCI patients, sampled over 2 to 6 months, in a patient-specific manner as well as compared with trauma patients diagnosed with acute urinary tract infections (UTI). The sample sources were urinary pellets (UP) from all subjects, and catheter biofilm extracts (CB) from SCI patients. Bioinformatic protein network and western blot analyses served to corroborate evidence of protein and cell differentiation changes in the urinary tract of SCI patients. Results: More than 50 proteins with functional or structural roles in the epidermal cornified envelope were quantitatively increased in proteomic profiles from three SCI patients. This included stress response keratins and proteins involved in keratin crosslinking, e.g. transglutaminases and small proline-rich proteins, suggesting occurrence of keratinizing squamous epithelial metaplasia. Protein co-expression network analyses supported epithelial trans-differentiation changes. Nearly thirty proteins with gastro-intestinal epithelial cell expression specificity were enriched in proteomic profiles from a single SCI patient. Among those were mucin-2 and sucrase-isomaltase, secreted proteins detected in samples for only that patient via western blots. This finding was consistent with intestinal epithelial metaplasia. Conclusions and clinical relevance: Without using invasive cystoscopy and histopathology, proteomic analyses from easily available UP and CB samples allowed us to infer cell differentiation changes in urothelial tissues of SCI patients with chronic infections, supporting a concept of clinical relevance for urothelial metaplasia screening, a precursor stage of urothelial neoplasms.

molecular biology↗

bioRxiv2026

A Distal Super-Enhancer Regulate CD47 Expression and Promotes Macrophage-Mediated Phagocytosis of Ovarian Cancer Cells

CD47 is an innate immune checkpoint that can protect tumor cells from macrophage-mediated clearance, but the regulatory mechanisms underlying its expression in ovarian cancer (OC) remain incompletely understood. Here, we investigated the epigenetic regulation of CD47 expression in OC. Single-cell and spatial transcriptomic analyses indicated preferential CD47 expression in malignant epithelial cells. Integration of publicly available epigenomic datasets revealed a distal regulatory region with enhancer-associated features across ovarian cancer models and HGSOC patient samples. A genome-wide CRISPR-Cas9 screen further implicated PITX2 and EP300 as regulators of CD47 expression. Chromatin immunoprecipitation assays showed PITX2 and EP300 occupancy at candidate enhancer elements within this CD47 regulatory region. Comparative epigenomic analyses suggested that features of this regulatory landscape are also present in fallopian tube epithelial cells and become more prominent in OC. Together, these findings support a PITX2-EP300 regulatory axis associated with CD47 expression and provide evidence for its potential contribution to tumor immune evasion.

cancer biology↗

bioRxiv2026

Extracellular water withdrawal drives disease resistance in the phyllosphere

A central question in immunity is how hosts arrest pathogen growth. Diverse plant pathogens create a water-soaked niche in host tissue essential for pathogenesis, yet how water shapes infection outcome is unknown. Using genetics and hyperspectral imaging, we show that extracellular water status is rate-limiting for both compatible and incompatible interactions. We find that the hypersensitive response of effector-triggered immunity (ETI) is, mechanistically, a desiccation event. Water loss imposes osmotic stress that arrests bacterial division while the pathogen remains alive and metabolically active, rather than killing it. Restoring apoplastic water reverses this stasis and licenses growth despite intact immune signaling and cell death. Water status, not immune signaling per se, gates pathogen growth. This reframes ETI as a controlled desiccation mechanism and identifies hydration as a decisive lever on disease outcome.

plant biology↗

bioRxiv2026

Atypical immunity induced by extracellular water in plants

Microbial pathogens require nutrients and water to support their growth and proliferation. Pathogen-mediated resource acquisition is orchestrated by the secretion of virulence factors that have evolved a diversity of forms (from effector proteins to small toxins), but which have converged in function (resource acquisition). A key observable virulence mechanism employed by a large number of microbial pathogens to cause disease is to induce a water-rich niche in the extracellular space (i.e. the apoplast) of their host, known as water-soaked lesions. Given the ubiquity of this virulence mechanism, we asked whether plants respond to pathogen-induced extracellular water to activate immune programs. We find that inducing a water-soaked apoplast induces an atypical transcriptional response, yet results in a functional immune response that restricts pathogen growth as effectively as canonical pattern-triggered immunity. Genetic and functional analyses reveal a role for the immune phytohormone salicylic acid (SA) in mediating apoplastic water-induced immunity (AWII). These results suggest that plants engage in an immune-priming program in response to apoplastic water accumulation, suggesting that the pathogenic niches induced during infection may be perceived as danger signals.

plant biology↗

bioRxiv2026

Overexpression of miR-424(322)/-503 induces severe dilated cardiomyopathy by regulating the fatty acid oxidation gene expression program

Fatty acid oxidation (FAO) is a major energy source in the adult heart, and disruption of cardiac metabolism is closely associated with heart failure. Here, we investigated the effects of cardiac-specific overexpression of the H19X-encoded miR-424(322)/-503 cluster using an inducible transgenic mouse model. Sustained miR-424(322)/-503 overexpression caused rapid metabolic and functional deterioration, with early impairment of fatty acid oxidation. Short-term induction reduced FAO activity and downregulated genes involved in lipid metabolism, while glycolytic enzyme activity remained largely unchanged. Continued miR-424(322)/-503 expression subsequently led to severe dilated cardiomyopathy characterized by ventricular dilation, wall thinning, fibrosis, reduced contractility, and high mortality. Importantly, disease progression was dependent on the level and duration of miR-424(322)/-503 expression, as intermittent or lower-dose induction delayed cardiac dysfunction and prolonged survival. Withdrawal of miR-424(322)/-503 expression after the onset of dysfunction promoted substantial functional recovery. Together, these findings identify miR-424(322)/-503 as a potent regulator of cardiac metabolic reprogramming that disrupts fatty acid metabolism and drives progressive heart failure.

molecular biology↗

bioRxiv2026

From vehicles to wildlife: transferable deep learning for trajectory generation

Realistic simulation of animal movement is fundamental to conservation, habitat modeling, and ecological scenario evaluation. Traditional approaches struggle to capture multi-scale trajectory dynamics, while generative deep learning for complete trajectory simulation remains largely unexplored in ecology due to data scarcity. We show that a diffusion model pre-trained on millions of vehicle GPS trajectories can be fine-tuned on hundreds of seabird central-place foraging trips to simultaneously generate ecologically realistic trajectories for five species and six breeding colonies. The fine-tuned model consistently outperforms four state-of-the-art baselines (GAN, VAE, HMM, iSSF) across movement metrics spanning step dynamics, spatial distribution, and behavioral temporality, with comparable or shorter computation times. Domain transfer reaches full performance in 35 minutes versus 7 hours from scratch, and conditioning on species and colony enables generalization to unseen combinations from as few as 10 trajectories. These results establish cross-domain transfer learning as a new paradigm for data-efficient generative animal movement modeling.

bioinformatics↗

bioRxiv2026

Mechanistically informed adaptive dosing for cancer immunotherapy using AI-guided decision making

Optimizing dose and schedule remains a central challenge in oncology drug development, particularly for immunotherapies where fixed dosing regimens often fail to account for patient specific heterogeneity in tumor-immune dynamics. Here, we present a hybrid quantitative systems pharmacology-reinforcement learning-Monte Carlo Tree Search (QSP-RL-MCTS) framework for personalized immunotherapy dosing that formulates dose selection as a sequential decision-making problem. The approach integrates a mechanistic QSP model of prostate cancer immunotherapy, transcriptomics informed virtual patient populations and data driven AI system comprising reinforcement learning and Monte Carlo tree search. Reinforcement learning is used to learn adaptive generalized dosing policies that optimize treatment outcomes across the population, while Monte Carlo Tree Search provides forward-looking evaluation of RL predicted dosing trajectories to refine patient-specific decisions. On benchmarking against fixed dosing regimens of ipilimumab, the remission rate of the proposed model (95.2%) was comparable to the highest fixed dosing regimen of 10 mg/kg per dose while the median total dose (72 mg/kg) of the proposed model designed regimen was comparable to the lowest fixed dosing regimen of 3 mg/kg per dose. The model is generalizable across different dosing protocols and can be extended to predict optimal dose under different therapeutic scenarios. Analysis of the learned dosing trajectories enables stratification of patients into distinct response groups and identifies drug activity rate as the dominant determinant of long-term treatment outcome. These results demonstrate how mechanistically guided artificial intelligence can transform population-level dose optimization into patient-specific, biologically interpretable treatment strategies for precision immuno-oncology.

systems biology↗

bioRxiv2026

Transition of a Yeast Endosymbiont from a Free-living to Host-reliant Lifestyle Through Gene Loss and Horizontal Gene Transfer

Endosymbiosis is widespread throughout the tree of life. Understanding how the transition of a bacterial endosymbiont from facultative to host-dependent obligate life occurs is an important question for defining the origin of endosymbiosis. A novel gram-positive bacillus, Brevibacillus sp. TJ4 was isolated from the nitrogen-fixing yeast Rhodotorula mucilaginosa JGTA-S1, which houses several endobacteria within its cells. TJ4 can survive independently of yeast but exhibits genomic and metabolic features characteristic of an evolving endosymbiont, slowly assuming a host-dependent, obligate lifestyle. The TJ4 genome contains several incomplete pathways for carbohydrate, amino acid, vitamin, and cofactor metabolism, which is reflected in its increased reliance on host-derived nutrients and auxotrophy compared with that of other Brevibacillus spp. Comparative genomics revealed widespread genome rearrangements, loss of synteny, and multiple cross-genus and inter-kingdom horizontal gene transfer (HGT) events in TJ4 compared to other Brevibacillus spp. These HGTs include the acquisition of genes from bacteriophages and co-resident endobacteria of JGTA-S1. One such horizontally acquired gene, Type II 3-dehydroquinate dehydratase (AroQ), appears to have originated from the Rhodotorula host itself. This acquisition functionally restores the shikimate pathway in strain TJ4, as evidenced by the phylogenetic placement of AroQ from TJ4 within the clade of fungal AroQ homologs. Potential exploitation of the host JGTA-S1 appears to be a probable mode of endosymbiosis of TJ4, an evolving endosymbiont that we named Brevibacillus rhodotorulae sp. nov.

microbiology↗

bioRxiv2026

Automated detection of blink reflexes evoked by optogenetic stimulation of TRPV1-expressing corneal nociceptors in transgenic mice

BackgroundConventional rodent models for the study of corneal pain commonly evoke eye blink reflex using methods that indiscriminately activate polymodal nociceptors, mechanoreceptors, and thermoreceptors at temporal resolutions that dont closely match the sub-second timescale of underlying neural dynamics. New methodWe introduce a novel automated behavioral paradigm for detecting blink reflexes in transgenic TRPV1-ChR2-EYFP mice, enabled by cell-type-specific, millisecond-precision optogenetic stimulation of corneal nociceptors (490 nm light). Using multi-feature quantification, we achieve robust automated detection using univariate and multivariate classifiers. ResultsTRPV1-ChR2-EYFP mice exhibited blink reflexes to high-intensity blue light (490 nm, 10 ms pulses) in a threshold-dependent manner (N=3). Blink probability was 77.1 {+/-} 17.1% at high intensity (2.77 mW/mm2) versus 4.2 {+/-} 4.2% at low intensity (0.46 mW/mm2). Red light (638 nm) produced no intensity-dependent change. Noxious air puff evoked blinks in >95% of trials under all conditions. DeepLabCut-based pose estimation extracted six features quantifying the blink reflex, enabling automated detection with [≥]98% accuracy using univariate and multivariate classifiers. Comparison with existing methodsUnlike conventional air puff paradigms, this optogenetic approach enables precise, cell-type-specific stimulation of corneal nociceptors, supporting automated analysis of blink responses at sub-second resolution. ConclusionsThis video tracking behavioral method using machine learning algorithms that accurately classify blink versus no-blink enables high-throughput and observer-independent empirical assessment of blink reflex, suggestive of corneal pain. Moreover, inducing blink reflex in TRPV1-ChR2 mice using high-intensity blue light also demonstrates nociceptive-specific behavioral responses analogous to somatosensory optogenetically-evoked hindpaw pain in the same animal genotype.

neuroscience↗

bioRxiv2026

A Dual-Function Guanidinium Scaffold that Couples Copper Sequestration with Redox Protection in Wilson disease

Wilson disease (WD) is caused due to mutations in the copper ATPase gene ATP7B, that result in accumulation of labile copper pools and the consequent disruption of cellular redox homeostasis through uncontrolled copper-mediated reactive oxygen species generation. Current therapies mainly depend on high-affinity copper chelation to lower metal burden which sometimes also strip copper from cuproproteins and may disturb physiological copper-dependent processes. It also does not directly suppress pathological copper reactivity i.e., free radical generation, a major driver of WD progression. To overcome these limitations, we have rationally designed Gua-Cu-3, a C-symmetric guanidinium-based molecule that can chelate labile copper without metal stripping from cuproproteins due to moderate binding affinity and it has intrinsic antioxidant activity within a single nanosheet-forming supramolecular self-assembly. Spectroscopic, calorimetric, and computational analyses revealed controlled multivalent copper coordination (Kd = 95.4 M) while radical-scavenging and hydroxyl-radical inhibition assays further revealed potent redox-regulatory activity. In cellular models of copper overload, Gua-Cu-3 treatment reduces ATP7B trafficking from trans-Golgi network, confirming effective intracellular copper sequestration. This was accompanied by a marked reduction in oxidative stress, reduction of translocation of Nrf2 in nucleus and of HO-1 expression, thereby limiting lipid peroxidation which leads to restoration of cellular homeostasis, including improved lysosomal integrity, reduced endoplasmic reticulum stress, decreased mitochondrial superoxide levels, and diminished apoptosis. Importantly, the protective effects extended, beyond cultured cells, Gua-Cu-3 attenuates oxidative stress in ATP7B-homolog-deficient C. elegans and rescues copper-induced developmental defects in zebrafish, outperforming D-penicillamine, which is currently in use for Wilson disease management. These findings establish Gua-Cu-3 as a molecularly designed supramolecular copper-reactivity buffer that couples-controlled copper sequestration with redox regulation which is distinct from conventional copper depletion and provides a framework for treating Wilson disease and other disorders associated with metal dyshomeostasis and oxidative stress.

Cell Biology↗

bioRxiv2026

Breaking the bottleneck: self-supervised deep learning framework for fully automated fossil CT segmentation

Semantic segmentation of domain-specific imaging data where labelled training examples are scarce and foreground-background contrast is low remains an open challenge in deep learning applied to science. Palaeontological computed tomography (CT) exemplifies this problem: digitally isolating fossilised bone from surrounding rock matrix is labour-intensive ([≥]100 hrs/dataset), subjective, and often reliant on expensive proprietary software, creating a "segmentation bottleneck" that prevents large-scale and rapid processing of CT data collections. Here we present a self-supervised, end-to-end framework combining SimCLR v1 contrastive pretraining with deterministic pseudo-label generation and U-Net refinement to fully automate fossil CT segmentation without manual annotation. Using 50,626 CT images from the Middle Jurassic Kilmaluag Formation spanning amphibians, reptiles, dinosaurs, and early mammals, the framework achieved a Dice coefficient of 93.66% and IoU of 82.42% on a held-out specimen not seen during training, comparable to the highest Dice and IoU values reported in recent Deep Learning-based fossil CT segmentation studies. Cross-taxon generalisation was validated geometrically on six fully external specimens, achieving sub-voxel mesh agreement with manually thresholded references. By eliminating the annotation requirement that has limited prior deep learning approaches in palaeontology, this framework reduces per-specimen processing from [~]100 person-hours to 6 hrs (one-time UNet training) +1-3 minutes (mesh generation per specimen), an essential first step towards batch processing and analysis of CT data for large-scale comparative and quantitative analyses.

paleontology↗

bioRxiv2026

Cell Mechanics Regulate Membrane Tubulation-Driven Trogocytosis in Adherent Cells

Trogocytosis is a widespread and physiologically important process in which one cell ingests fragments of another. It has been observed in diverse biological contexts, such as in Entamoeba histolytica, a human enteric parasite that nibbles host intestinal cells via trogocytosis, thereby invading the tissue and leading to lethal extra-intestinal disease, and in macrophages on interaction with adherent tumor monolayers. Despite its physiological relevance, knowledge of trogocytosis with adherent cells remains elusive. Here, we established a monolayer-based trogocytosis assay and uncovered a distinct membrane-tube-mediated trogocytic mechanism operative in adherent cells. We characterized it into four sequential events: contact, membrane tubulation, stretching, and scission. By targeting the proteic constituents of target cell stiffness, we show that trogocytic output exhibits a non-monotonic dependence on the viscoelastic properties of the target cell, with maximal uptake occurring in an intermediate mechanical regime. Further, we integrated live-cell trogocytosis observations with a viscoelastic model-based theoretical framework to propose a tube-breaking mechanism across distinct mechanical subtypes. Finally, using micropatterning, we demonstrated that target cell shape influences trogocytosis kinetics. This work suggests that trogocytosis is sensitive to the mechanical state of the target cell.

cell biology↗

bioRxiv2026

Exploiting NDH-2 Vulnerability: Quinolines as Antitubercular Agents

Mycobacterium tuberculosis possesses a flexible metabolic system helping it to survive inside the host. The type II NADH dehydrogenase, composed of Ndh and NdhA, essential for bacilli, is a promising drug target. Based on ATP depletion values, two quinoline scaffolds were shortlisted after screening of a library of drug like molecules. Structurally, both 64-9C and 64-9D carry ester moieties at the 5- and 8-positions of the quinoline core, respectively. Ease to re-synthesise 64-9D resulted in synthesis of a focused library of compounds, with MIC values of 0.25-4 g/mL, consistent with ATP depletion. These compounds exhibited bactericidal activity against non-replicating mycobacteria, and showed potent efficacy against multidrug-resistant isolates. Altered, intracellular NADH/NAD+ ratio and reduced respiration was indicative of oxidative phosphorylation inhibition. Inhibition of the purified recombinant NDH protein uncompetitively, SNPs in gene encoding NDH-2 for selected one step mutants and, molecular modelling of 4FQN and 2FQN validated NDH-2 as a target for these compounds. The derivative 2FQN exhibited dose-dependent bactericidal efficacy in mice, underscoring the potential of the series as a promising anti-tuberculosis candidates.

microbiology↗

bioRxiv2026

Effects of Phthalate Metabolite Mixture Exposure on Mouse Oocyte Development

Phthalates are pervasive endocrine-disrupting chemicals widely used in consumer products. The wide use of many phthalates results in chronic human exposure to complex mixtures rather than single compounds. Despite extensive studies on individual compounds, the combined effects of phthalate metabolites on oogenesis remain poorly understood. Here, we developed a precise microinjection-based single-oocyte toxicological assay to examine the impact of a defined phthalate metabolite mixture on meiotic progression. Phthalate mixture exposure markedly impaired oocyte maturation, as most oocytes failed to extrude the first polar body. Mechanistic analyses revealed severe meiotic defects, including disrupted spindle morphology, chromosome misalignment, disorganized actin cytoskeleton, and impaired mitochondrial function, accompanied by excessive reactive oxygen species (ROS) accumulation and DNA damage. Single-cell transcriptomic profiling further identified differentially expressed genes enriched in biological processes related to exocytosis, secretory pathway regulation, and cytoskeletal organization, as well as in MAPK, JAK-STAT, cGMP-PKG, and GnRH signaling pathways that are essential for follicular development and oocyte maturation. Together, these findings demonstrate that combined phthalate exposure directly compromises female gamete quality and underscore the importance of evaluating mixture effects when assessing risks to womens reproductive health.

cell biology↗

bioRxiv2026

Magnetoactive hydrogels to probe curvature-directed endothelial cell mechanosensing

The vascular system exhibits complex, non-planar geometries that become further distorted during pathological remodeling, including arterial tortuosity and aneurysms. Although hemodynamic shear stress is a well-established regulator of vascular function, the direct effects of curvature as an intrinsic geometric cue remain poorly defined. This is largely because existing in vitro models are static and fail to capture the dynamic changes that accompany disease progression. To address this gap, we used a magnetoactive hydrogel platform that enables real-time, on-demand curvature of endothelial monolayers to reproduce clinically established tortuosity metrics. Using this system, we found that elevated curvature increased nuclear localization of yes-associated protein (YAP), with the strongest response in convex relative to concave regions of highly tortuous endothelial monolayers. This mechanosensitive response was accompanied by reduced VE-Cadherin junctional thickness and increased membrane localization of endothelial nitric oxide synthase. Together, these findings identify local curvature, independent of shear stress, as a regulator of endothelial cell mechanosensing and function, and establish a dynamic hydrogel platform for isolating geometric regulation from shear stress inputs in vascular mechanobiology.

bioengineering↗

bioRxiv2026

CD180 identifies chemoresistant stem-like blasts and reveals a KMT2A-driven vulnerability in acute myeloid leukaemia

Relapse and chemoresistance remain major challenges in paediatric acute myeloid leukaemia (PAML), particularly in KMT2A-rearranged (KMT2A-r) subtypes where conventional markers such as CD34 are often absent, complicating measurable residual disease (MRD) detection. Leukaemia stem/regenerating cells (LSC/LRC) drive disease initiation, progression, and relapse, sharing stemness and chemoresistance properties that make them critical therapeutic targets. Using high-dimensional spectral flow cytometry, we identified CD180, a Toll-like receptor-like surface protein, as highly expressed on blasts and stem-like populations in KMT2A-r AML, while near absent on normal haematopoietic stem cells (HSCs). PAML KMT2A-r exhibits an unconventional immunophenotype dominated by CD34-CD180 populations. Integrated single-cell transcriptomics and functional profiling revealed CD180high clusters enriched for quiescence, oxidative phosphorylation, and KMT2A/LSC stemness signatures. CD180 cells demonstrated robust leukaemia-initiating capacity in xenograft models and persisted through therapy, re-emerging at relapse with phenotypic plasticity. Epigenomic analysis showed CD180 is a direct transcriptional target of the KMT2A::MLLT3 fusion complex, regulated by intragenic enhancers and downregulated by menin and BET inhibitors. Longitudinal single-cell analysis confirmed persistence and clonal evolution of CD180 populations during treatment and relapse, underscoring their mechanistic role in chemoresistance and disease progression. In summary, CD180 marks dynamic, relapse-driving populations in KMT2A-r PAML, persists through therapy, and importantly is near absent on normal HSCs, offering a selective therapeutic window. These findings position CD180 as a clinically actionable biomarker for MRD detection and a compelling therapeutic target for eradicating chemoresistant, stem-like cells in paediatric AML. Main PointsO_LICD180 marks chemoresistant, relapse-driving stem-like blasts in KMT2A-r paediatric AML, overcoming CD34-based MRD limitations. C_LIO_LIAbsent on normal HSCs, CD180 is a KMT2A::MLLT3 target and actionable for MRD, relapse prediction, and CD180-directed therapies. C_LI NoveltyThis study introduces CD180 as a novel biomarker and therapeutic target in AML, particularly KMT2A-rearranged subtypes where conventional markers are often absent. Unlike MRD strategies focused on bulk blasts, CD180 marks chemoresistant, stem-like populations driving relapse, critical reservoirs poorly defined in paediatric AML. This work fills a major gap in prognostic assessment and therapy by enabling precise detection of relapse-driving cells and offering a selective therapeutic window.

cancer biology↗

bioRxiv2026

Hydroperiod buffers water surface decline in dryland wetlands: A 36-year analysis in Hwange National Park

Drylands are experiencing increasingly intense and frequent drought events due to climate change. Wetlands in drylands are therefore under increasing pressure as their inundation regimes are altered. In southern African savannas, wetlands are often the only sources of free water for the ecosystem. Changes in the hydroperiod may alter vegetation and water surfaces, which could be early signals of desertification in their immediate vicinity. To investigate trends in surface cover around wetlands, we applied linear multispectral unmixing to Landsat pixels located near wetlands in Hwange National Park. We assessed spatial gradients in vegetation, water, and bare soil dynamics from 1986 to 2022. The studied wetlands were also grouped by hydroperiod to test whether the response of each surface cover differed with the reliability of the water resource. Our results show a significant decrease in the water fraction of wetlands with short hydroperiods, which was significantly negatively correlated with increasing temperature. Furthermore, water fraction was significantly positively correlated with vegetation fraction. This correlation suggests that vegetation could be affected if water surfaces continue to decline. Finally, this study is the first to demonstrate a decline in water surfaces in Hwange National Park, with potential implications for wildlife conservation.

ecology↗