Biology subjects

Liu, X.

Publications and source records attributed to Liu, X..

At least 181 records · Page 10Linked to original sources

bioRxiv2026

Microbial network rewiring mediates the function-biosafety trade-off in transboundary Pamir lakes

The Pamir Plateau is a transboundary water tower whose source lakes serve as critical biogeochemical hubs with implications for downstream freshwater security. However, it remains unclear how environmental shifts in these high-altitude lakes reshape the microbial communities that drive ecosystem functioning and water safety. Here, we conducted a multi-omics survey across 20 lakes spanning Chinese and Tajikistani Pamir. Our results revealed that prokaryotes exhibited lower diversity but higher among-lake connectivity in China, while eukaryotes showed higher diversity but stronger dispersal limitation. These contrasting biogeographic responses triggered profound rewiring of microbial associations. Under intensified anthropogenic pressures, Chinese cross-kingdom networks decoupled from environmental constraints and became more centralized and complex. Conversely, Tajikistani lakes maintained more modular networks governed by hydrochemical filtering. Critically, this rewiring mediated a trade-off between multifunctionality and potential biosafety risk, with higher element cycling abundances in Chinese lakes, whereas Tajikistani lakes harbored larger biosafety burden dominated by virulence, pathogen, and toxic-algae potential. Incorporating network topology also substantially improved the prediction of these ecological consequences. These findings highlight the importance of network-informed monitoring and management strategies to safeguard ecosystem sustainability in transboundary Pamir lakes under global change.

microbiology↗

bioRxiv2026

The P3018S disease variant reveals how dynein's trailing motor sets ensemble velocity.

Mutations in the cytoplasmic dynein heavy chain (DYNC1H1) underlie a range of neurodevelopmental disorders yet how individual variants perturb dynein function remains poorly understood. We characterize the disease-associated P3018S mutation, located in the AAA4 module and within the Lis1-interacting region of the motor. Dynein-dynactin-BicD2 (DDB) complexes containing P3018S dynein move at half the wild-type velocity and generate reduced stall forces but retain the ability to assume the inhibitory phi conformation that Lis1 suppresses, respond to Lis1, and assemble into higher-order force-generating states. Several Schizosaccharomyces species, which lack Lis1, naturally encode a serine at this position, suggesting evolutionary relevance for dynein activation. Using mixed wild-type-mutant assemblies, we find that the dynein occupying the trailing position on dynactin dictates ensemble velocity, and that the leading dyneins LIC enhances trailing-motor velocity by [~]130%, revealing a mechanism for leading-to-trailing motor stimulation within multi-dynein assemblies.

biophysics↗

bioRxiv2026

The Magnaporthe oryzae Effector AvrPii Attenuates Rice Immunity by Targeting the Calcium-Associated ANK Protein AVIN8

Rice blast, caused by the fungus Magnaporthe oryzae, poses a severe threat to global rice production. Although numerous M. oryzae effectors have been identified, the molecular mechanisms remain poorly understood. The effector AvrPii triggers ETI upon recognition by NLR receptor Pii and has been shown to target host exocytosis and oxidative metabolic pathways to suppress immunity. Here, we identify AVIN8 (AvrPii-interacting protein 8) as a new target of AvrPii. AVIN8 is an ankyrin-repeat (ANK) protein localized to the plasma membrane and nuclear envelope, with sequence similarity to known ANK calcium channels. AVIN8 expression is induced during early M. oryzae infection. Overexpression of AVIN8 enhances blast resistance, whereas its silencing increases susceptibility. AVIN8 promotes chitin-triggered ROS production in a Ca2+-dependent manner. In contrast, AvrPii impairs Ca2+ influx and chitin-triggered ROS burst. Our findings reveal a virulence strategy in which M. oryzae effector AvrPii hijacks the Ca2+ influx-associated ANK protein AVIN8 to suppress early calcium and PTI signaling in rice.

plant biology↗

bioRxiv2026

A chromatin accessibility map of pea aphid brain and embryo identifies tissue-specific regulatory elements

The pea aphid (Acyrthosiphon pisum) is an important model organism for studying complex biological traits, including wing polyphenism and host-symbiont interactions, yet its regulatory genomic landscape remains largely uncharacterized. Here we present the first genome-wide chromatin accessibility map of the pea aphid, generated using the assay for transposase-accessible chromatin followed by sequencing (ATAC-seq). We profiled open chromatin regions (OCRs) in adult brains and late-stage embryos from winged and wingless morphs maintained under solitary or crowded conditions. We also paired ATAC-seq with RNA-seq in embryonic samples to examine the relationship between chromatin accessibility and gene expression. Libraries showed a high abundance of reads from the aphid endosymbionts Spiroplasma and Buchnera, reflecting preferential Tn5 transposase insertion into nucleosome-free bacterial DNA. After computational removal of these reads, the remaining aphid-mapping libraries displayed hallmarks of high-quality ATAC-seq data. We identified a consensus set of 37,127 OCRs enriched at promoters and distal regulatory elements, with substantial overlap with computationally predicted enhancers and enrichment for transcription factor binding motifs. Tissue identity was the dominant driver of chromatin variation, accounting for 85% of variance along the first principal component, with 19,513 differentially accessible regions distinguishing brain from embryo samples. By contrast, differences associated with wing morph or crowding treatment were modest. Promoter accessibility was significantly and positively correlated with gene expression genome-wide. Together, these data constitute a foundational regulatory genomics resource for the pea aphid and establish a framework for mechanistic studies of gene regulation in this ecologically and economically important insect.

genomics↗

bioRxiv2026

Integrated Collagen Architecture and Composition Improve Risk Stratification in Triple-Negative Breast Cancer

PurposeTriple-negative breast cancer (TNBC) exhibits substantial clinical heterogeneity, with some patients experiencing early recurrence and poor survival despite similar clinicopathologic features. We sought to determine whether quantitative measures of intratumoral collagen architecture and composition derived from standard histopathologic specimens can identify patients at risk of recurrence and adverse survival outcomes. Experimental DesignWe analyzed a retrospective cohort of 79 TNBC tumors assembled into a tissue microarray using a multimodal computational pathology framework integrating Massons Trichrome staining with COL1 and COL3 immunohistochemistry. Collagen architecture was quantified using fiber-based image analysis and unsupervised clustering, while collagen composition was assessed using a normalized COL3:COL1 ratio. Associations with recurrence-free interval (RFI) and overall survival (OS) were evaluated using Kaplan-Meier analysis, restricted mean survival time (RMST), and Cox proportional hazards modeling. ResultsUnsupervised analysis identified four distinct collagen architectural states, which were consolidated into low-risk and high-risk groups based on recurrence patterns. High-risk collagen architecture was associated with significantly worse long-term RFI (log-rank p=0.025; RMST difference 10.1 months). Independently, a higher COL3:COL1 ratio was associated with improved OS (log-rank p=0.042; RMST difference 9.4 months). Integration of architectural and compositional biomarkers further refined risk stratification, identifying a subgroup with high-risk architecture and low COL3:COL1 ratio that exhibited the poorest survival outcomes. Notably, collagen-based stratification identified patients with divergent outcomes not readily predicted from tumor stage alone. ConclusionsQuantitative assessment of intratumoral collagen architecture and composition provides clinically meaningful prognostic information in TNBC and enables stratification of recurrence and survival risk. These findings support extracellular matrix phenotyping as a practical and scalable computational pathology approach for refining risk assessment in TNBC. Translational RelevanceTriple-negative breast cancer (TNBC) remains clinically challenging due to heterogeneous outcomes that are not fully captured by standard clinicopathologic variables. In this study, we demonstrate that quantitative features of intratumoral collagen architecture and composition, derived from routine pathology specimens, provide clinically meaningful prognostic information. Collagen-based biomarkers, including distinct collagen architectural phenotypes and the COL3:COL1 ratio, identify patient subgroups with distinct recurrence and survival outcomes, particularly among individuals whose risk is not adequately predicted by conventional staging. Importantly, these features can be extracted from widely available histological stains and immunohistochemistry, supporting the potential integration into existing pathology workflows. These findings support the tumor microenvironment as an underutilized source of biomarkers and suggest that extracellular matrix-based phenotyping may improve risk stratification and inform clinical decision-making in TNBC.

cancer biology↗

bioRxiv2026

Satellite Glial Cells Drive Homeostatic Synaptic Structural Plasticity in Sympathetic Neurons

Sympathetic neuronal (SN) activity critically regulates the development and function of peripheral organs and tissues. The demonstration of activity-dependent modulation of SN output suggests that compensatory forms of plasticity could contribute to maintaining the stability of sympathetic circuits. Such plasticity mechanisms could act to restrain SN hyperactivity, a key driver of hypertension in humans and in the spontaneously hypertensive rat (SHR). In this study we examined how long-term changes in activity impact synaptic properties in postnatal sympathetic neuron cultures using chemogenetic and pharmacological manipulations and by examining the effects of enhanced activity of SHR neurons. We showed that bidirectional changes in neuronal activity resulted in homeostatic shifts in synaptic density to counteract long-term activity manipulations. In the absence of sympathetic satellite glial cells (SGCs) there was no synaptic compensation in the cultures. Direct chemogenetic activation of SGCs was sufficient to drive a decrease in synaptic sites and neuronal activity, while glial inhibition blocked activity-dependent synaptic compensation, demonstrating a role for the SGCs in homeostatic regulation of synaptic properties. We found that the SGCs responded to cholinergic signaling by downregulating the expression of the synaptic regulators NGF and TNF, suggesting that reciprocal signaling between SNs and SGCs acts to stabilize sympathetic output during long-term changes in circuit activity. Finally, we showed that these plasticity mechanisms are disrupted in postnatal SHR neurons, with an attenuated neuronal response to glia signaling during synapse formation and activity-dependent plasticity. Taken together, this work describes a new homeostatic activity-dependent plasticity mechanism in the peripheral nervous system.

neuroscience↗

bioRxiv2026

A data-driven redefinition of global biodiversity hotspots

The 36 global biodiversity hotspots harbor a disproportionate share of the worlds endemic species, making their conservation critical for planetary health. Traditionally hotspots were defined as ecoregions with [≥]1,500 endemic vascular plant species and >70% natural habitat loss; this relied heavily on expert judgment, with subjective assessments of endemism and habitat loss applied. Challenges in defining endemism, quantifying habitat loss, and the global unevenness in available vascular plant data have hindered hotspot identification over the past decades. Here, we built a global dataset of 150,487 rare vascular plants, identified from 88.1% of the worlds known vascular species, and recognize hotspots based on their richness using three complementary conservation targets and algorithms. We then quantified natural habitat loss and habitat fragmentation using high-resolution remote sensing data and assessed the diversity and distribution of terrestrial vertebrates within these newly identified hotspots. Our data-driven method recovered all the 36 established global biodiversity hotspots, revised 17, and identified 11 new hotspots spanning diverse ecosystems across six continents. These 47 hotspots cover 26.63% of global land area, yet contain 83.8% of rare vascular plants, 92.4% of mammals, 96.1% of birds, 87.8% of reptiles, and 95.0% of amphibians. Collectively, they encompass >89% of terrestrial vertebrates classified as IUCN threatened species. Only 10 hotspots have undergone [≥]70% habitat loss, and the lack of a consistent relationship with habitat fragmentation suggests that this criterion is not globally applicable. Effectively protecting [~]27% of Earths land could theoretically safeguard >89.8% of threatened terrestrial species and >67% of threatened terrestrial species hotspot area, assuming effective protection of the identified biodiversity hotspots. Targeted conservation efforts within these global biodiversity hotspots can meet the established biodiversity targets of the Kunming-Montreal Global Biodiversity Framework as well as post-2030 biodiversity targets. Most importantly, our framework enables conservation scientists to iteratively identify and update global biodiversity hotspots in step with growing global biodiversity data.

ecology↗

bioRxiv2026

NFIC-mediated CaSR endocytosis defines a hyperactive TOMM20highCHGAhigh oxyphil cell state as a pathological driver of autonomous secondary hyperparathyroidism

Secondary hyperparathyroidism (SHPT) is a debilitating complication of chronic kidney disease. Its clinical management is frequently compromised by calcimimetic resistance, a refractory state primarily driven by the progressive downregulation of the membrane calcium-sensing receptor (CaSR). Despite the centrality of CaSR as a therapeutic target, the mechanisms governing its aberrant expression and membrane localization remain incompletely elucidated. Here, we generated a single-cell transcriptomic atlas of human parathyroid tissues from SHPT and primary hyperparathyroidism (PHPT) patients, uncovering a unique stromal-immune niche that is specifically induced by uremic stress in SHPT. Our data also observed a striking dissociation between CaSR mRNA and its abundance as a membrane protein in SHPT tissues. Pseudotime trajectory analysis showed a progressive decline in CaSR pathway activity and a concomitant increase in endo-lysosomal activity along the trajectory, terminating in pathological oxyphil cells as the endpoint of chief cell differentiation in SHPT. Mechanistically, Nuclear Factor I C (NFIC) transcriptionally activated clathrin light chain B (CLTB) and Ras-related protein Rab7a (RAB7A) to trigger clathrin-mediated endocytosis and lysosomal degradation of CaSR, thus reducing its membrane abundance. This degradative program was further validated by multiplex immunofluorescence in TOMM20highCHGAhigh pathological oxyphil cells in human SHPT tissues. To translate these mechanistic findings into a clinically actionable strategy, we repurposed the clinically approved lysosomal inhibitor hydroxychloroquine (HCQ) to block this CaSR degradation pathway. In patient-derived xenograft (PDX) mouse models, co-administration of HCQ and cinacalcet acted synergistically to restore membrane CaSR expression, normalize serum PTH and calcium levels and suppress parathyroid tumor growth more effectively than monotherapies. Collectively, our single-cell-guided study identifies an NFIC-driven endo-lysosomal program as a previously unrecognized mechanism underlying CaSR downregulation and calcimimetic resistance in SHPT, and establishes HCQ repurposing as a clinically tractable therapeutic strategy for patients with refractory SHPT.

cell biology↗

bioRxiv2026

3'UTR Insertion of a Directed-Evolved RNA Element for Enhanced Translation

Translation efficiency remains a major limitation for RNA therapeutics. Conventional optimization targets the 5 untranslated region (5 UTR), while the 3 UTR is viewed mainly as a stabilizing element. Here, we demonstrate that the 3 UTR can be rationally engineered to actively enhance translation. Using an intracellular directed-evolution platform based on the SINEB2 element, we identified RNA modules P51 and its compact variant P51t3,which markedly increased protein output without affecting mRNA levels. P51t3 consistently boosted expression two- to six-fold across plasmid, in vitro transcribed mRNA, and recombinant AAV systems. Mechanistic studies revealed that P51t3 binds ribosomal protein RPL39, recruiting 60S subunits to the initiation site through the natural closed-loop translation model. By integrating evolutionary selection with 3 UTR design, this work redefines the 3 UTR as an active translational enhancer and provides a broadly applicable regulatory element for next-generation mRNA and gene-delivery therapeutics.

molecular biology↗

bioRxiv2026

Helminth-remodeled microbial indole-3-lactic acid drives AhR-dependent disease tolerance

Helminths systemically suppress host immunity, yet whether they impose immune tolerance by rewiring host-associated microbial metabolism remains unclear. Here we show that Trichinella spiralis infection remodels intestinal tryptophan metabolism to generate an AhR-dependent regulatory immune state. T. spiralis infection enriched the commensal bacterium Ligilactobacillus murinus, which converted tryptophan into indole-3-lactic acid (ILA), a microbial metabolite that directly engaged the aryl hydrocarbon receptor. Antibiotic-mediated microbiota depletion abolished infection-induced ILA accumulation, AhR activation and Treg/Th17 rebalancing, whereas fecal microbiota transplantation from infected donors or supplementation with L. murinus or ILA restored these effects. Pharmacological blockade or genetic deletion of AhR eliminated the ability of T. spiralis, L. murinus and ILA to restrain LPS-induced cytokine-storm-like lung inflammation, establishing AhR as an essential host node in this circuit. Extending these findings to viral inflammatory disease, oral ILA improved survival and reduced pulmonary immunopathology in SARS-CoV-2-infected K18-hACE2 mice. Re-analysis of human COVID-19 metabolomic data further revealed reduced circulating ILA in severe disease. These findings define a helminth-remodeled microbial tryptophan metabolic pathway that promotes disease tolerance and identify the ILA-AhR axis as a candidate postbiotic strategy for limiting hyperinflammatory tissue injury.

immunology↗

bioRxiv2026

Proteogenomics of Blumeria hordei supports RNA and protein coding innovative potential derived from transposable elements

Some filamentous plant-pathogenic fungi have comparably large genome sizes within the fungal kingdom due to the proliferation of transposable elements (TEs). Blumeria hordei (Bh), the causal agent of the powdery mildew disease on barley, is a filamentous obligate biotrophic fungus. Compared to other ascomycetes, it contains a low number of genes but a high genomic TE content of approximately 75%. Yet, a comprehensive understanding of the contribution of TEs to the RNA and protein landscape of Bh is lacking. Here, we use Bh as a model to study transcripts and proteins derived from genes and individual TEs. Therefore, we created two high-quality genome assemblies of the German Bh isolate TUM1 and the Australian Bh isolate AUS1. We applied deep proteomics with mass spectrometry, long-read and short-read sequencing on both DNA and RNA. Based on these multi-omic resources, we completed nearly gapless genome assemblies, new gene and TE annotations, and effector predictions. Using long-read RNA sequencing, we detected extensive co-transcription of TEs and genes as TE-gene chimeric transcripts. We identified previously unpredicted splice variants or genes, partially supported by proteomics. The intergenic and TE genomic space of Bh TUM1 gives rise to thousands of transcripts and several novel TE-derived proteins that lack from previous TE protein predictions. Together, this supports an existing potential for expression of novel transcripts and proteins from highly abundant TEs in the Bh genome.

plant biology↗

bioRxiv2026

Tree diversity intensifies soil microorganism-tree interactions

O_LIA productivity-driven higher nutrient demand of trees in diverse mixtures is frequently reported. Yet, it remains unclear how tree diversity influences microorganisms-plants interactions, in which microbes facilitate tree nutrient acquisition in exchange for carbon (C) to meet the resource demand of both. C_LIO_LIUsing a long-term tree diversity experiment in the subtropics, we assessed microbial investment in C-, nitrogen (N)-, and phosphorus (P)-acquiring enzymes in litter and mineral soil, testing the effects of tree species richness and mycorrhizal type (arbuscular (AM)- vs. ectomycorrhizal (EcM)-associated tree species). C_LIO_LIWith increasing tree species richness, microbial investment in C acquisition decreased, while investment in N and/or P acquisition increased in litter and in mineral soil. In mineral soil of AM-associated tree mixtures, ecoenzymatic stoichiometry revealed a shift from microbial investment in C toward P acquisition as tree species richness increased. C_LIO_LIOur findings suggest that tree diversity strengthens microbe-tree interactions in terms of C-for-nutrient exchange. This highlights the key role of soil microorganisms, particularly in AM symbiosis, shaping tree diversity-biogeochemical feedbacks. C_LI

ecology↗

bioRxiv2026

Lineage-specific lncRNAs critically determine cross-species differences in tumors

Diverse mouse models have been generated to study human tumors. Although mouse and human tumors share similar differentially expressed genes and cancer hallmarks, many drugs that work in mice fail in humans. What makes mouse models poorly recapitulate human tumors remains unclear. We postulate that transcriptional regulation by lineage-specific long noncoding RNAs (LS lncRNAs) critically determines cross-species and cross-tumor differences. To test this hypothesis, we identified LS lncRNAs, predicted their target genes, integrated 9,058 RNA-seq samples from 13 human tumors and their mouse counterparts, and analyzed transcriptional regulation by LS lncRNAs across cellular contexts. LS lncRNAs substantially and tumor-specifically reconfigure transcription and signaling, and strongly influence cancer immunity and anti-cancer drug efficacy. These results provide systematic information for exploring and interpreting human tumor mouse models and for identifying human- and tumor-specific diagnostic and therapeutic targets. They also present an analytical approach applicable to other human diseases and their mouse models.

systems biology↗

bioRxiv2026

Ancestral Musaceae karyotype reconstruction provides insights into chromosome evolution and bract coloration

The banana family (Musaceae) exhibits remarkable diversity in both karyotype structure and bract coloration, yet the evolutionary dynamics of chromosomes and the genomic and regulatory basis underlying color diversification remain poorly understood. Here, we present a telomere-to-telomere (T2T), gap-free genome assembly of Musa exotica, an ornamental species with brightly colored bracts occupying an early-branching lineage within sect. Callimusa (Musa L.). By integrating this high-quality genome with other available Musaceae genomes, we reconstruct the ancestral Musaceae karyotype (AMK) for the first time, inferring a haploid chromosome number of n = 17. Comparative genomic analyses reveal recurrent, highly complex lineage-specific inter-chromosome rearrangements across extant Musaceae lineages, leading to inferred stepwise reductions in chromosome number to n = 11, 10, and 9. Notably, closely related species share similar rearrangement patterns, suggesting conserved evolutionary trajectories shaped by lineage-specific structural remodeling. Strikingly, rearrangement-associated regions are enriched for functionally important genes, particularly structural genes (CHS and F3H) and regulatory transcription factors (MYB and bHLH) involved in the anthocyanin biosynthesis pathway. Integrative transcriptomic and regulatory analyses further demonstrate coordinated activation of anthocyanin biosynthetic genes (CHS, CHI, F3'5'H, and ANS) in bracts, with expression divergence largely decoupled from gene dosage and predominantly driven by transcriptional regulation. Co-expression analyses reveal extensive MYB- and bHLH-enzyme interactions, underscoring their central role in modulating pathway activity and bract coloration diversity. Collectively, our findings suggest a link between genome structural evolution to trait diversification, offering a refined framework for understanding genome evolution and phenotypic diversification in Musaceae and other monocots. SignificanceWe reconstructed the ancestral Musaceae karyotype and revealed extensive lineage-specific chromosome rearrangements underlying karyotype evolution. Rearrangement-associated regions are enriched for anthocyanin biosynthetic and regulatory genes, suggesting that genome structural evolution may have contributed to bract coloration diversification in Musaceae. Integrative transcriptomic analyses further indicate that variation in anthocyanin-mediated bract coloration is more closely associated with transcriptional regulation than with gene dosage alone.

evolutionary biology↗

bioRxiv2026

HIV-1 interactions with sialic acid-binding bacterial lectins promote virus infectivity in vitro and mucosal transmission in humanized mice

Most HIV-1 transmission occurs at mucosal surfaces, which are colonized by the host microbiota. However, interactions between HIV and bacteria or bacterial products derived from the human microbiome are poorly characterized, and their biological consequences are largely unexplored. Here, we evaluated the effects of sialic acid-binding lectins expressed by bacterial species ubiquitous in the human microbiota on HIV-1 infectivity using viruses produced in 293T cells and human primary cells. We demonstrated that these bacterial lectins enhanced HIV-1 infectivity in a sialoglycan-dependent manner. Specifically, Siglec-like binding region lectins (SLBR-N, SLBR-H, and SLBR-B) from Streptococcus gordonii and Staphylococcal superantigen-like lectins (SSL3, SSL4, and SSL11) from Staphylococcus aureus increased HIV-1 infectivity to varying extents, depending on lectin type and virus strain. Among these lectins, SLBR-N exhibited the greatest potency, corresponding with its superior ability to bind virions and promote virus-cell attachment. This enhancing activity was observed for direct infection of TZM-bl reporter cells and primary CD4+ T cells, as well as trans-infection in the presence or absence of the mannose-binding host lectin DC-SIGN. Importantly, these findings were corroborated in vivo using humanized mice, in which pre-exposure to SLBR-N promoted rectal HIV-1 transmission and increased viral burdens in plasma and splenic cells. Collectively, the data show sialoglycan-binding bacterial lectins as microbial factors that can enhance HIV-1 transmission at mucosal surfaces, highlighting a potential direct role for the microbiota in modulating HIV-1 acquisition risk. Author SummaryHIV is commonly transmitted from one person to another across mucosal surfaces, such as those lining the genital and rectal tracts, which are densely populated by bacteria that make up the human microbiota. Yet, surprisingly little is known about how these bacteria and the molecules they produce influence HIV infection. In this study, we investigated a group of bacterial proteins known as sialic acid-binding lectins that are expressed by common members of the human microbiome: Siglec-like binding region lectins from Streptococcus gordonii and superantigen-like lectins from Staphylococcus aureus. Using multiple HIV strains and several types of target cells, we demonstrate that lectin binding to HIV can increase virus attachment to target cells and thereby enhance infection, although the magnitude of this effect varies among lectins and virus strains. Lectin binding also facilitates HIV spread from cell to cell and promotes mucosal HIV infection in a humanized mouse model, resulting in a higher viral burden in the blood and tissues. These findings identify bacterial lectins as important factors that can influence HIV infection and implicate a potential role for the human microbiota in determining susceptibility to HIV infection.

microbiology↗

bioRxiv2026

The crop pathogen Blumeria hordei exhibits genome-wide pervasive selective and neutral sweepstakes reproduction signatures.

The fungal crop pathogen Blumeria hordei, causal agent of powdery mildew on barley, presents life-history and epidemiological characteristics, as well as and selective pressures due to modern agriculture leading to expected sweepstakes reproduction, that is highly skewed offspring distributions. Using genome-wide polymorphism data and population genomics inferences, we aim to 1) infer the past demographic history and the strength of sweepstakes reproduction in B. hordei, and 2) quantify the contributions of these selective and neutral processes in the genome. An new inference method based on Neural Posterior Estimation and diversity and linkage disequilibrium statistics was developed and tested on simulated and B. hordei genomic data. We confirm that B. hordei exhibits a moderate sweepstakes reproduction (-parameter of 1.6). We highlight that the Site Frequency Spectrum (SFS) appears sensitive to the joint occurrence of sweepstakes and recent demographic changes, which may caution on the reliability of the SFS to infer sweepstakes reproduction. We then scan the genome for selective sweeps, adjusting the significance thresholds of the methods for demographic history and sweepstakes reproduction, thereby yielding a counterintuitive result. When conditioning the significance threshold for sweep detection on simulations under sweepstakes and demography, a very large number of putatively selected regions is found (11.6% of the genome). We suggest that sweepstakes reproduction in B. hordei is due to 1) neutrality (clonal/sexual phases and Boom-and-Bust cycles) generating a genome-wide level of background noise in the coalescent genealogies, and 2) selective sweepstakes due to pervasive positive selection. Our findings have important implications for both population genomic methodology and our understanding of pathogen evolution.

evolutionary biology↗

bioRxiv2026

Vessel-Resolved Mapping of Perivascular Spaces Reveals Hierarchical Neurofluid Organization In Vivo

Perivascular spaces (PVS) are central to cerebrospinal fluid (CSF)-interstitial fluid (ISF) exchange in the brain, yet their brain-wide organization and in vivo accessibility remain poorly resolved due to limited spatial resolution and contrast specificity of existing imaging approaches. Prior gadolinium (Gd)-enhanced MRI studies demonstrate global tracer distribution but yield spatially diffuse signals that do not resolve PVS at the level of individual vessels. Here we introduce an ultra-high-resolution dual-contrast MRI framework that enables vessel-resolved mapping of PVS across the whole brain in vivo. This approach combines ultra-high-field imaging, an implantable radiofrequency coil for enhanced local sensitivity, and intraventricular Gd delivery to achieve sufficient contrast and spatial specificity for detecting vessel-associated perivascular signal. Using this framework, we show that PVS are hierarchically organized along vascular trees, extending from major surface arteries into deep cortical and subcortical regions. Signal patterns along arterial branches and junctions indicate that PVS follows vascular topology. Quantitative analysis reveals that only a subset of penetrating vessels ([~]6%) exhibits detectable PVS signal, indicating heterogeneous organization across vascular networks independent of vessel caliber. Widespread detection of PVS, including in the hippocampus, further demonstrates that ventricularly delivered tracers access a distributed, vessel-associated perivascular network in vivo. These results establish an anatomical framework for mapping perivascular transport pathways across the brain, bridging global tracer imaging with vessel-resolved organization, and enabling investigation of how vascular architecture and fluid dynamics shape CSF-ISF exchange.

neuroscience↗

bioRxiv2026

Mitochondrial uracil DNA glycosylase contributes to nuclear base excision repair

The universally conserved enzyme uracil-DNA N-glycosylase (UNG) plays a central role in maintaining genome stability. It functions as the initiating factor in uracil base excision repair (UBER) by catalyzing the removal of uracil lesions in genomic DNA, a necessary first step in restoring genome integrity after hydrolytic deamination of cytosine to uracil or misincorporation of deoxy-uridine monophosphate during replication. Although methods have been developed to study UBER in vitro and in cellulo, none provide a quantitative readout of UNG activity on the chromosomal DNA of living cells. To address this gap, we created an UNG biosensor (U-report) that utilizes a modified cytosine base editor to generate a targeted genomic uracil lesion in a fluorescent reporter for C-to-U editing activity. UNG activity ablation through uracil DNA glycosylase inhibition (Ugi) or UNG-knockout results in elevated reporter fluorescence. Isoform-specific knockouts show that mitochondrial UNG1 also contributes to UBER of nuclear DNA. Our studies establish a real-time biosensor for quantification of chromosomal DNA uracil excision activity in living cells and, in support of prior studies, indicate that both UNG isoforms should be addressed in small molecule inhibitor development programs. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/721890v2_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@8e6566org.highwire.dtl.DTLVardef@a33b03org.highwire.dtl.DTLVardef@774663org.highwire.dtl.DTLVardef@ae1814_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗