Biology subjects

Qian, Z.

Publications and source records attributed to Qian, Z..

At least 19 recordsLinked to original sources

bioRxiv2026

WTAP-mediated epitranscriptomic program in alveolar macrophages confers prolonged protection against postinfluenza bacterial pneumonia

Secondary bacterial infections remain an intractable problem of seasonal influenza, primarily due to the depletion and defunctionalization of alveolar macrophages (AMs). Here, we described that N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, critically orchestrates trained immunity (TRIM) establishment in AMs. Influenza A virus (IAV)-trained AMs maintained low Wilms tumor 1-associated protein (WTAP) expression and reduced global m6A deposition for over two months. Mechanistically, this IAV-induced m6A decrease promotes TRIM by enhancing the RNA stability of phagocytic and metabolic genes, thereby boosting antibacterial function. Mimicking this m6A reduction pharmacologically or genetically recapitulates the IAV-trained TRIM phenotype, which improves phagocytosis and protects mice from secondary infection. Clinically, elevated WTAP in AMs correlates with impaired phagocytosis and disease severity in COVID-19 and COPD. These findings for the first time unveil how respiratory virus infection shapes AM TRIM via epitranscriptomic reprogramming, and offer prospective strategies for the prevention and treatment of post-viral bacterial complications.

immunology↗

bioRxiv2026

Photothermal Recycling Biosensing for Continuous, Sensitive Molecular Quantification

Continuous biochemical sensing provides valuable insights into an individuals physiological state and the mechanisms underlying pathophysiological changes. However, most existing bioanalytical methods are not compatible with continuous biochemical sensing. A major technical challenge lies in achieving rapid measurement readouts while maintaining high specificity and sensitivity in complex biological fluids. Sensitive molecular detection typically requires slow analyte-binder dissociation and long incubation to reach equilibrium, whereas rapid and frequent measurements demand fast association-dissociation kinetics that are difficult to reconcile for low-abundance analytes. To address this challenge, we introduce a sensing mechanism termed photothermal recycling (PTR), which mimics the thermal cycling process in polymerase chain reaction. Using plasmonic photothermal effects, PTR rapidly recycles binders to enable frequent measurements. We demonstrate a digital PTR assay capable of multi-hour biochemical monitoring with subpicomolar(pM) sensitivity in buffer, diluted serum, and saliva. This approach leverages localized thermal energy to dynamically modulate biomolecular recognition, offering a new bioanalytical paradigm for continuous biochemical sensing across diverse application settings.

bioengineering↗

bioRxiv2026

Detection of Somatic Point Mutations Directly from Spatial Transcriptomics Enables in vivo Spatiotemporal Lineage Tracing

Spatial transcriptomics reveals tissue organization but lacks in vivo lineage-tracing methods applicable to humans. We introduce SpaceTracer, a computational framework that accurately detects somatic single-nucleotide variants (SNVs) directly from spatial transcriptomics data. By leveraging naturally occurring somatic SNVs, SpaceTracer reconstructs cellular phylogenies within native tissue architecture, enabling the mapping of lineage spread, migration, lineage-coupled expression changes and lineage-aware local interactions. Applied to human cutaneous squamous cell carcinoma, it traced tumor initiation and progressions, uncovered widespread pre-invasive migration of dedifferentiated epithelial cells and characterized mutant B cells migrating from tertiary lymphoid structures (TLS) into the tumor boundary. The framework also reconstructed developmental lineages across multiple tissues and identified tissue-resident mutant immune cells. SpaceTracer thus provides a perturbation-free platform for high-resolution spatiotemporal lineage tracing, offering a transformative tool for elucidating complex biological systems--especially tumor-immune ecosystems--with direct implications for advancing cancer immunotherapy.

bioinformatics↗

bioRxiv2025

Drift, selection and convergence in the evolution of a nonribosomal peptide

Nonribosomal peptides play important roles in microbial ecology and medicine, for example as toxins and antibiotics such as penicillin1. Like ordinary proteins, nonribosomal peptides are subject to evolutionary change, which is driven by rampant recombinations of their synthetases2. This makes it difficult to study the evolutionary histories of nonribosomal peptides, because recombination is a serious challenge for phylogenetic inference3. Here we use recombination-aware phylogenetics and ancestral sequence reconstruction to retrace the evolution of GameXPeptides, nonribosomal peptides entomopathogenic bacteria use to kill their insect prey4. By untangling the complex histories of their synthetases, we discover dozens of new GameXPeptides and show striking patterns of structural convergence. In analogy to classic statistical test for natural selection acting on nucleotide mutations, we develop a similar test for whether selection acts to fix recombinations. We provide statistical and experimental evidence of both neutral genetic drift and natural selection in the diversification of GameXPeptides. GameXPeptides variants rapidly evolved highly insect specific toxicities, suggesting that their diversification may be driven by an evolutionary arms race. Our work suggests that small, fast evolving alteration to nonribosomal peptides can overcome host resistance on short timescales, with important implications for the evolution of resistance evading antibiotics.

evolutionary biology↗

bioRxiv2025

Hierarchical taxonomic constraints shape bacterial nitrogen cycling across functional and molecular scales

Microbes are essential for global nitrogen cycling, yet the extent to which taxonomic identity constrains functional potential remains poorly quantified. Using 73,472 representative bacterial genomes, we establish a multi-scale quantitative framework revealing systematic, hierarchical relationships between taxonomic identity and nitrogen cycling functional potential. Hierarchical variance decomposition reveals that taxonomy explains 20-46% of functional variation across six nitrogen pathways, with the strongest constraints for dissimilatory nitrite reduction to ammonium (46.1%) and nitrogen fixation (44.2%), both negatively correlated with functional prevalence. K-means clustering identifies four class-level functional archetypes (Functionally Inactive, Diversified, Integrated, and Specialized) among 77 bacterial classes. 1,281 genera resolve into five ecological strategies differentiated by their nitrogen retention versus loss capabilities, exhibiting strong phylogenetic signals. Cross-scale validation demonstrates 78.7% genus-level conformity to class-level archetypes, confirming hierarchical functional organization. Molecular evolutionary analysis of 13 genes reveals sequence conservation as a dimension partially independent of pathway-level functional constraints. Paradoxically, the functionally most constrained pathway exhibits only moderate sequence conservation (nrfA: 9th/13 genes), while a moderately constrained pathway shows exceptional conservation (napA). Four constraint-conservation patterns demonstrate that gene-specific structural and ecological factors generate evolutionary rate variation independently of taxonomic associations. Our results establish a hierarchical framework in which taxonomic constraints set baseline functional potential, ecological trade-offs shape strategy diversification, and molecular evolution modulates gene-level conservation patterns across biological scales. This framework establishes quantitative baselines that enable probabilistic inference of nitrogen cycling capabilities from taxonomic composition, with potential applications in amplicon-based community analysis, targeted cultivation, and biogeochemical modeling. ImportanceA fundamental challenge in microbial ecology is inferring functional potential from taxonomic data--a relationship widely assumed but never rigorously quantified. Resolving this is critical because while amplicon sequencing provides cost-effective taxonomic profiling, functional characterization requires expensive metagenomics, limiting large-scale biogeochemical studies. We provide the first systematic quantification demonstrating that taxonomic identity explains 20-46% of nitrogen cycling functional variation, operating hierarchically from class to genus level. Crucially, we reveal that taxonomic constraints operate at both functional distribution and molecular evolution levels as partially independent dimensions, indicating distinct evolutionary mechanisms. This work establishes quantitative foundations for taxonomy-based functional prediction, enabling researchers to extract functional insights from readily available taxonomic surveys. As reference databases expand, this framework will enhance predictive capabilities for nitrogen cycling and broader biogeochemical processes.

genomics↗

bioRxiv2025

An EEG-based Multi-Scale Hybrid Attention and Squeeze Network for objective taste assessment

Taste perception is central to flavor experiences. Electroencephalography (EEG) signals carry rich information about taste perception. Because these neural data are independent of verbal reports and bypassing conscious filtering, EEG holds promise as a neural-sensing platform for objective taste representation. However, taste-evoked EEG signals exhibit complex spatiotemporal and spectral dynamics that require advanced computational approaches to decode effectively. This study developed an EEG-based Multi-Scale Hybrid Attention and Squeeze Network (MHASNet) for taste evaluation. EEG signals evoked by distinct taste stimuli were recorded, a dedicated taste-EEG dataset was compiled, and a novel deep learning architecture, MHASNet, was designed to classify these signals. MHASNet synergistically integrates multi-scale convolutions to capture temporal dynamics across different time scales, dual-attention mechanisms to localize discriminative brain regions and electrode positions, and a squeeze-and-excitation module to optimize frequency-band contributions-collectively enabling precise extraction of taste-specific neural signatures. Results showed that the proposed model achieved superior performance across five taste categories (sweet, sour, salty, bitter, and tasteless), with 94.33% accuracy, 91.37% F1-score, 91.89% precision, and 92.07% recall. These results surpass benchmark models while maintaining millisecond-level inference latency suitable for real-time applications. By complementing subjective evaluations and instrumental analyses, the model offers an objective, neurophysiology-based solution for taste evaluation.

neuroscience↗

bioRxiv2025

Dual Targeting of IKKβ and NR4A1 for AML Therapy

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with poor clinical outcomes and limited therapeutic options. Aberrant activation of the IKK{beta}-NF-{kappa}B pathway occurs in approximately 40% of AML cases and contributes to leukemogenesis. However, pharmacological inhibition of IKK{beta} has been limited by serious toxicities, including neutrophilia. Here we identify IKK{beta} and NR4A1 as critical drivers of AML progression in certain models and develop a proteolysis-targeting chimera (PROTAC) capable of degrading the proteins. Although NR4A1 has previously been described as a tumor suppressor in AML, our findings demonstrate that NR4A1 exhibits oncogenic functions in some AMLs of the (pro)monocytic lineage. Notably, elevated expression of IKK{beta} and NR4A1 in AML is associated with poor clinical outcomes, playing non-redundant oncogenic roles in AML. To therapeutically target IKK{beta} and NR4A1, we designed and synthesized a series of celastrol-based PROTACs that exploit celastrols ability to bind both IKK{beta} and NR4A1. Among these compounds, the lead A9 induces potent cytotoxicity in multiple AML cell lines and primary AML samples through cereblon E3 ligase-dependent degradation of IKK{beta} and/or NR4A1. In vivo, A9 suppresses leukemia progression in a KMT2A::MLLT3 AML mouse model without inducing neutrophilia, supporting PROTAC-mediated degradation of IKK{beta} and NR4A1 as a promising therapeutic strategy. Plain language summaryAcute myeloid leukemia (AML) is a predominant form of blood cancer with devastating consequences in both young and adult populations. Despite some advances in AML treatment over the last decade, there is still an unmet medical need to develop new drugs for difficult-to- treat AMLs. We discover that two proteins, namely IKK{beta} and NR4A1, play important roles in promoting the AML disease and could be associated with more severe AML subtypes. To target and destroy those proteins within AML cells, we employ a novel targeted protein degradation approach, which involved design, synthesis, and screening of PROTAC drugs, to discover a drug possessing pronounced AML cell killing activity by virtue of IKK{beta} and NR4A1 degradations. The drug also significantly reduces AML progression in mice without any noticeable adverse effects. Our current efforts involve more comprehensively testing the benefit of the drug (and its analogs) in a wide range of clinically relevant AML models. Key PointsO_LIIKK{beta} and NR4A1 are clinically relevant drivers of AML pathogenesis. C_LIO_LIA novel celastrol-based PROTAC can effectively degrade IKK{beta} and/or NR4A1 to potentially treat AML. C_LI

cancer biology↗

bioRxiv2025

The genomic and transcriptional landscape of the spinal cord H3K27-altered diffuse midline glioma suggests the potential therapeutic strategy

Diffuse midline glioma with H3K27-altered (DMG) is a lethal pediatric malignancy that primarily occurs in the brainstem of children. In adults, DMG arising in the spinal cord is rarely reported and remains poorly understood. The cellular architecture and clinical outcomes of DMG vary depending on the tumors location. To dissect the genomic and transcriptional architecture of a cohort of spinal cord DMG patients, we conducted whole-exome sequencing and single-cell RNA sequencing on 19 tumor samples from 7 patients. We identified previously underappreciated stem-like cells associated with hypoxia in malignant tumor cells, which were present in all samples of spinal cord DMG but absent in published intracranial DMG, corroborating cellular heterogeneity based on tumor location. We discovered that tumor-associated myeloid cells constituted the largest population of non-malignant cells in adult spinal cord DMG. Our research revealed a transition from microglia to macrophages, characterized by enhanced cell-to-cell interactions mediated through the VEGF signaling pathway network. Notably, we found that epigenetic agents can repress the expression of hypoxia-related gene programs in patient-derived spinal cord DMG cultures and inhibit cell proliferation in vitro. Collectively, our study reveals a crucial anatomical dimension that DMG exhibits a location-specific genomic and transcriptional landscape despite shared H3K27 alterations, providing the paradigm for developing precision therapeutic strategies that extend beyond DMG to other molecularly defined yet anatomically divergent malignancies.

cancer biology↗

bioRxiv2025

Reference-guided genome assembly at scale using ultra-low-coverage high-fidelity long-reads with HiFiCCL

Population genomics using short-read resequencing captures single nucleotide polymorphisms and small insertions and deletions but struggles with structural variants (SVs), leading to a loss of heritability in genome-wide association studies. In recent years, long-read sequencing has improved pangenome construction for key eukaryotic species, addressing this issue to some extent. Sufficient-coverage high-fidelity (HiFi) data for population genomics is often prohibitively expensive, limiting its use in large-scale populations and broader eukaryotic species and creating an urgent need for robust ultra-low coverage assemblies. However, current assemblers underperform in such conditions. To address this, we propose HiFiCCL, the first assembly framework specifically designed for ultra-low-coverage high-fidelity reads, using a reference-guided, chromosome-by-chromosome assembly approach. We demonstrate that HiFiCCL improves ultra-low-coverage assembly performance of existing assemblers and outperforms the state-of-the-art assemblers on human and plant datasets. Tested on 45 human datasets ([~]5x coverage), HiFiCCL combined with hifiasm reduces the length of misassembled contigs relative to hifiasm by an average of 21.19% and up to 38.58%. These improved assemblies enhance germline structural variant detection, reduce chromosome-level mis-scaffolding, enable more accurate pangenome graph construction, and improve the detection of rare and somatic structural variants based on the pangenome graph under ultra-low-coverage conditions.

bioinformatics↗

bioRxiv2025

The denitrosylase SCoR2 controls cardioprotective metabolic reprogramming

Acute myocardial infarction (MI) is a leading cause of morbidity and mortality, and therapeutic options remain limited. Endogenously generated nitric oxide (NO) is highly cardioprotective, but protection is not replicated by nitroso-vasodilators (e.g., nitrates, nitroprusside) used in clinical practice, highlighting specificity in NO-based signaling and untapped therapeutic potential. Signaling by NO is mediated largely by S-nitrosylation, entailing specific enzymes that form and degrade S-nitrosothiols in proteins (SNO-proteins), termed nitrosylases and denitrosylases, respectively. SNO-CoA Reductase 2 (SCoR2; product of the Akr1a1 gene) is a recently discovered protein denitrosylase. Genetic variants in SCoR2 have been associated with cardiovascular disease, but its function is unknown. Here we show that mice lacking SCoR2/Akr1a1 exhibit robust protection in an animal model of MI. SCoR2 regulates ketolytic energy availability, antioxidant levels and polyol homeostasis via S-nitrosylation of key metabolic effectors. Human cardiomyopathy shows reduced SCoR2 expression and an S-nitrosylation signature of metabolic reprogramming, mirroring SCoR2-/- mice. Deletion of SCoR2 thus coordinately reprograms multiple metabolic pathways--ketone body utilization, glycolysis, pentose phosphate shunt and polyol metabolism--to limit infarct size, establishing SCoR2 as a novel regulator in the injured myocardium and a potential drug target. Impact statementMice lacking the denitrosylase enzyme SCoR2 demonstrate robust cardioprotection resulting from coordinate reprogramming of multiple metabolic pathways. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/642752v2_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@72bfbborg.highwire.dtl.DTLVardef@189cbc4org.highwire.dtl.DTLVardef@1a0cc51org.highwire.dtl.DTLVardef@1c61004_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2025

Stress-activated neuronal ensemble in the supramammillary nucleus stores anxiety but not memory

Anxiety is a prevalent negative emotional state induced by stress; however, the neural mechanism underlying anxiety is still largely unknown. We used acute and chronic stress to induce anxiety and test anxiety-like behavior; immunostaining, multichannel extracellular electrophysiological recording and Ca2+ imaging to evaluate neuronal activity; and virus-based neuronal tracing to label circuits and manipulate circuitry activity. Here, we identified a hypothalamic region, the supramammillary nucleus (SuM), plays important role in anxiety-like behavior. We then characterized a small ensemble of stress-activated neurons (SANs) that are recruited by stress. These SANs respond specifically to stress, and their activation robustly increases anxiety-like behavior in male mice. We also found that ventral subiculum (vSub)-SuM projection but not dorsal subiculum (dSub)-SuM projections encode anxiety-like behavior and that inhibition of these vSub-SuM projections has an antianxiety effect. These results indicate that the reactivation of stress-activated supramammillary cells and relevant neural circuits are important neural processes underlying anxiety-like behavior.

neuroscience↗

bioRxiv2024

RNA methylation controls stress granule formation and function during erythropoiesis

Stress granules (SGs) are crucial in RNA regulation, affecting cell fate and function. SGs contain RNAs, some of which can be methylated. We studied m6A RNA modifications during the human CD34+ HSPCs (hCD34+) differentiating into erythroid cells and found that mRNAs encoding many erythroid-specific proteins had decreased methylation during differentiation. Increased levels ALKBH5 demethylase during erythropoiesis controls the levels of the 3UTR methylation of these mRNAs. hCD34+ carrying ALKBH5 mutations demonstrated a block in erythropoiesis, and mass-spectrometry studies of the mutant cells showed decreased levels of SG proteins, including the core granule protein ATXN2. ALKBH5 directly regulates the methylation of the mRNA of ATXN2. ATXN2 overexpression accelerated the erythroid differentiation of HSPCs and rescued the erythroid differentiation of ALKBH5 mutant cells. Very few SGs are found in normal human erythroid progenitors. SGs accumulated substantially in ALKBH5 mutant cells, and surprisingly overexpression of ATNX2 reduced SG numbers to normal. Polysome analysis demonstrated m6A-modified RNAs to be enriched in the pre-polysome fractions that were less translated. This work establishes a mechanism by which during stress, ATXN2 facilitates the release of SG-stored m6A-modified RNAs including erythroid-specific and SG-enriched RNAs that are loaded onto functional ribosomes, allowing better translation and accelerated erythroid differentiation during stress.

cell biology↗

bioRxiv2024

Single-cell atlas of developing mouse palates reveals cellular and molecular transitions in periderm cell fate

Cleft palate is one of the most common congenital craniofacial disorders that affects childrens appearance and oral functions. Investigating the transcriptomics during palatogenesis is crucial for comprehending the etiology of this disorder and facilitating prenatal molecular diagnosis. However, there is limited knowledge about the single-cell differentiation dynamics during mid- and late-palatogenesis, specifically regarding the subpopulations and developmental trajectories of periderm, a rare but critical cell population. Here we explore the single-cell landscape of mouse developing palates from E10.5 to E16.5. We systematically depict the single-cell transcriptomics of mesenchymal and epithelial cells during palatogenesis, including subpopulations and differentiation dynamics. Additionally, we identify four subclusters of palatal periderm and construct two distinct trajectories of cell fates for periderm cells. Our findings reveal that Claudins and Arhgap29 play a role in the non-stick function of the periderm before the palatal shelves contact, and Pitx2 mediates the adhesion of periderm during the contact of opposing palatal shelves. Furthermore, we demonstrate that epithelial-mesenchymal transition (EMT), apoptosis, and migration collectively contribute to the degeneration of periderm cells in the medial epithelial seam. Taken together, our study suggests a novel model of periderm development during palatogenesis and delineates the cellular and molecular transitions in periderm cell determination.

genomics↗

bioRxiv2024

A bone-derived protein primes rapid visual escape via GPR37 receptor in a subpopulation of VTA GABAergic neurons

Rapid escape against visual threats is critical for survival. Whether it requires a permissive mechanism is unknown. Here, we show that osteocalcin (OCN), a protein produced by bone and persisted in the brain, primes rapid visual escape response by increasing excitability of VTA GABAergic neuron subpopulation via OCN-GPR37-cAMP-THIK-1 (K2P13.1) pathway. Knock-out of OCN or its receptor GPR37, and conditional knock-out of GPR37 in VTA GABAergic or glutamatergic neurons caused delayed escape. Reconstituting OCN-GPR37 signaling specifically in VTA was sufficient to restore normal response. Single-cell transcriptomics combined with electrophysiology showed that OCN decreases potassium currents in a subpopulation of VTA GABAergic neurons via GPR37-induced cAMP reduction and subsequent THIK-1 suppression. This elevation of excitability in VTA neuron subpopulation can be recapitulated by HM4Di, an inhibitory chemogenetic GPCR commonly used to suppress neuronal activity. Our study demonstrated that visual behavior requires a bone-derived protein that tunes electrophysiology of central nervous system neurons. Graph AbstractO_ST_ABSIn briefC_ST_ABSThe bone-brain axis regulates visual escape behavior. Osteocalcin (OCN), a small protein secreted by bone, plays a permissive role in rapid visual escape. This is achieved through GPR37 receptor expressed in a subpopulation of VTA GABAergic neurons. OCN-GPR37 signaling increases neuronal excitability by decreasing K+ current via THIK-1 channel suppression. HighlightsO_LIThe bone-derived protein osteocalcin and its receptor GPR37 in VTA are required for rapid visual escape response. C_LIO_LIGPR37 is expressed in a subpopulation of VTA GABAergic neurons and primes rapid visual escape. C_LIO_LIOsteocalcin-GPR37 signaling increases neuronal excitability by suppressing THIK-1 (K2P13.1) channel via cAMP reduction. C_LIO_LIActivation of HM4Di increases excitability of subpopulation of VTA GABAergic neurons and enhances rapid visual escape. C_LI O_FIG O_LINKSMALLFIG WIDTH=192 HEIGHT=200 SRC="FIGDIR/small/607510v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1b7ef5dorg.highwire.dtl.DTLVardef@c3eea2org.highwire.dtl.DTLVardef@167dd75org.highwire.dtl.DTLVardef@1fc5613_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

CellClear: Enhancing Single-cell RNA Data Quality via Biologically-Informed Ambient RNA Correction

Ambient RNA, caused by the pool of mRNA molecules released from lysed or dead cells in samples, poses persistent challenges to single-cell RNA sequencing data analysis, and leads to potential problems such as inaccurate classification of cell types and downstream functional analyses. Here we propose CellClear to estimate and remove the ambient RNA expression programs in single-cell RNA sequencing data. CellClear demonstrates significant increase in the accuracy of ambient gene expression correction comparing with state-of-art methods, without distorting native information of individual cell types.

bioinformatics↗

bioRxiv2024

ACE2-independent sarbecovirus cell entry is supported by TMPRSS2-related enzymes and reduces sensitivity to antibody-mediated neutralization

The COVID-19 pandemic, caused by SARS-CoV-2, demonstrated that zoonotic transmission of animal sarbecoviruses threatens human health but the determinants of transmission are incompletely understood. Here, we show that most spike (S) proteins of horseshoe bat and Malayan pangolin sarbecoviruses employ ACE2 for entry, with human and raccoon dog ACE2 exhibiting broad receptor activity. The insertion of a multibasic cleavage site into the S proteins increased entry into human lung cells driven by most S proteins tested, suggesting that acquisition of a multibasic cleavage site might increase infectivity of diverse animal sarbecoviruses for the human respiratory tract. In contrast, two bat sarbecovirus S proteins drove cell entry in an ACE2-independent, trypsin-dependent fashion and several ACE2-dependent S proteins could switch to the ACE2-independent entry pathway when exposed to trypsin. Several TMPRSS2-related cellular proteases but not the insertion of a multibasic cleavage site into the S protein allowed for ACE2-independent entry in the absence of trypsin and may support viral spread in the respiratory tract. Finally, the pan-sarbecovirus antibody S2H97 enhanced cell entry driven by two S proteins and this effect was reversed by trypsin. Similarly, plasma from quadruple vaccinated individuals neutralized entry driven by all S proteins studied, and use of the ACE2-independent, trypsin-dependent pathway reduced neutralization sensitivity. In sum, our study reports a pathway for entry into human cells that is ACE2-independent, supported by TMPRSS2-related proteases and associated with antibody evasion.

molecular biology↗

bioRxiv2024

BLADE-ON-PETIOLE interacts with CYCLOIDEA to fine-tune CYCLOIDEA-mediated flower symmetry in Monkeyflowers (Mimulus)

AbstractMorphological novelties, or key innovations, are instrumental to the diversification of the organisms. In plants, one such innovation is the evolution of zygomorphic flowers, which is thought to promote outcrossing and increases flower morphological diversity. We isolated three allelic mutants from two Mimulus species displaying altered floral symmetry and identified the causal gene as the orthologue of Arabidopsis BLADE-ON-PETIOLE. We found that MlBOP and MlCYC2a physically interact and this BOP-CYC interaction module is highly conserved across the angiosperms. Furthermore, MlBOP self-ubiquitinates and suppresses MlCYC2a self- activation. MlCYC2a, in turn, impedes MlBOP ubiquitination. Thus, this molecular tug-of-war between MlBOP and MlCYC2a fine-tunes the expression of MlCYC2a, contributing to the formation of bilateral symmetry flowers, a key trait in angiosperm evolution. One Sentence SummaryMolecular tug-of-war between MlBOP and MlCYC2a fine-tunes the expression of MlCYC2a, contributing to the bilateral flower symmetry formation.

developmental biology↗

bioRxiv2023

Variability in donor lung culture and relative humidity impact the stability of 2009 pandemic H1N1 influenza virus on nonporous surfaces

Respiratory viruses can transmit by multiple modes, including contaminated surfaces, commonly referred to as fomites. Efficient fomite transmission requires that a virus remain infectious on a given surface material over a wide range of environmental conditions, including different relative humidities. Prior work examining the stability of influenza viruses on surfaces has relied upon virus grown in media or eggs, which does not mimic the composition of virus-containing droplets expelled from the human respiratory tract. In this study, we examined the stability of the 2009 pandemic H1N1 (H1N1pdm09) virus on a variety of nonporous surface materials at four different humidity conditions. Importantly, we used virus grown in primary human bronchial epithelial (HBE) cultures from different donors to recapitulate the physiological microenvironment of expelled viruses. We observed rapid inactivation of H1N1pdm09 on copper under all experimental conditions. In contrast to copper, viruses were stable on polystyrene plastic, stainless steel, aluminum, and glass, at multiple relative humidity conditions, but greater decay on ABS plastic was observed at short time points. However, the half-lives of viruses at 23% relative humidity were similar among non-copper surfaces and ranged from 4.5 to 5.9 hours. Assessment of H1N1pdm09 longevity on nonporous surfaces revealed that virus persistence was governed more by differences among HBE culture donors than by surface material. Our findings highlight the potential role of an individuals respiratory fluid on viral persistence and could help explain heterogeneity in transmission dynamics. IMPORTANCESeasonal epidemics and sporadic pandemics of influenza cause a large public health burden. Although influenza viruses disseminate through the environment in respiratory secretions expelled from infected individuals, they can also be transmitted by contaminated surfaces where virus-laden expulsions can deposit. Understanding virus stability on surfaces within the indoor environment is critical to assessing influenza transmission risk. We found that influenza virus stability is affected by the host respiratory secretion in which the virus is expelled, the surface material on which the droplet lands, and the ambient relative humidity of the environment. Influenza viruses can remain infectious on many common surfaces for prolonged periods, with half-lives of 4.5-5.9 hours. These data imply that influenza viruses are highly persistent in indoor environments in biologically-relevant matrices. Decontamination and engineering controls should be used to mitigate influenza virus transmission.

microbiology↗