Biology subjects

Xiong, C.

Publications and source records attributed to Xiong, C..

At least 19 recordsLinked to original sources

bioRxiv2026

High frequency of apomixis in subterranean islands challenges macro-climatic models of geographical parthenogenesis

The Geographical Parthenogenesis (GP) hypothesis traditionally links apomixis to high-latitude and alpine regions, driven by a combination of thermal stress, UV radiation, and pollination barriers. At the core of the GP hypothesis is Bakers Law, which asserts the evolutionary advantage of autonomous reproduction during the colonization of isolated habitats, frequently linking this advantage to macro-climatic stress. By investigating reproductive modes in subtropical subterranean karst caves, we test the core assumption that macro-climatic stress is the primary driver of apomixis. Our results suggest that barriers to pollination drive a high frequency of apomixis independently of thermal stress or UV radiation. Furthermore, we find a complete phylogenetic turnover between high-elevation, open, apomict-rich habitats and mid-elevation cave environments. Taxonomic composition in these caves is dictated by pre-adaptations to deep shade combined with a lineage-specific predisposition for autonomous reproduction. We propose that the GP hypothesis may be overly influenced by habitat sampling bias. Broader, unbiased sampling could yield a more nuanced and predictive framework to explain variations in apomixis frequency, ultimately providing deeper insights into the role of asexual reproduction in evolution

evolutionary biology↗

bioRxiv2026

RBM6-mediated alternative splicing facilitates the adaptation of Eurasian avian-like H1N1 swine influenza virus

The Eurasian avian{square}like (EA) H1N1 swine influenza virus (SIV), derived from avian influenza viruses (AIV), poses a serious threat to public health due to its capacity for cross{square}species transmission and pandemic emergence. The molecular determinants underlying its replication advantage over AIV remain poorly defined. Here, we identify RNA{square}binding motif protein 6 (RBM6) as a novel host factor that differentially regulates the replication of EA H1N1 SIV and AIV. Mechanistically, RBM6 binds to the critical M901 site of the viral M segment, thereby modulating RNA splicing. Substitution of M901C with M901T markedly reduced RBM6 binding, impaired M segment splicing, and attenuated viral replication both in vitro and in vivo. Conservation analysis revealed that M901T is common in avian strains, whereas M901C is predominantly maintained in swine strains, underscoring M901C as a determinant of swine adaptation. Complementation experiments further demonstrated that swine RBM6, but not avian RBM6, restored EA H1N1 SIV replication. Taken together, our findings uncover a previously unrecognized role of RBM6 in shaping influenza virus replication and highlight the RBM6-M901C axis may serve as potential targets for controlling influenza virus adaptation and interspecies transmission.

microbiology↗

bioRxiv2026

Lactylation of Influenza Virus Polymerase Acidic Protein Promotes Viral Replication and Pathogenicity

Influenza virus poses a potential risk of triggering the next global pandemic. In-depth investigation into the mechanisms underlying influenza virus replication and pathogenicity will provide robust support for controlling influenza virus infection. Although post-translational modifications are known to regulate viral infection, the role of lactylation in influenza virus replication remains elusive. In this study, influenza virus ribonucleoprotein complex subunits are found to be lactylated. Specifically, ATAT1 promotes viral polymerase acidic protein (PA) lactylation and enhances viral replication. In contrast, SIRT1 mediates de-lactylation of PA and exerts an inhibitory effect on viral replication. Further investigations reveal lactylation of PA at residues K605 and K609 is essential for viral replication and pathogenicity. Mechanistically, PA K605/609 residues are localized at the interaction interface of the ANP32-mediated polymerase asymmetric dimer; mutation at these residues inhibits polymerase asymmetric dimerization, thereby impairing RNA production during viral genome replication. Collectively, this study uncovers a novel mechanism by which influenza virus hijacks host enzymes to mediate PA lactylation, and expands the molecular regulatory network of influenza virus infection.

microbiology↗

bioRxiv2025

Neural Mechanisms of Willed Attention Control

Cueing paradigms are commonly used to study the neural mechanisms of visual spatial attention control. In these paradigms, each trial starts with an external cue, which instructs the subject to pay covert attention to a spatial location in anticipation of an impending stimulus (instructed attention). Recent work has introduced a new type of cue which prompts the subject to spontaneously decide which spatial location to attend (willed attention). We studied the neural mechanisms of willed attention control by analyzing fMRI and EEG data recorded at two institutions (UF and UC Davis) using the same willed attention paradigm. The findings include: (1) both instructional cues and the choice cue activated the DAN, (2) the choice cue additionally activated a frontoparietal decision network consisting of dorsal anterior cingulate cortex (dACC), anterior insula (AI), anterior prefrontal cortex (APFC), dorsal lateral prefrontal cortex (DLPFC), and inferior parietal lobule (IPL), (3) the decision about where to attend can be decoded in frontoparietal decision network in choice trials but not in instructional trials, and (4) EEG alpha oscillation patterns immediately preceding the choice cue, but not the instructional cues, predicted the postcue direction of attention and the frontoparietal decision network activity. Based on these findings we proposed a model of willed attention control suggesting how the direction of visual spatial attention was decided upon in the absence of external instructions.

neuroscience↗

bioRxiv2025

Leaf microbiome assembly is linked to plant phylogeny

Background and AimsThe plant microbiome is considered as an extended part of the plant genome, and it provides key functions in regulating plant fitness, and stress tolerance. Plants and associated microbiomes have co-evolved over millennia, yet evidence for a strong influence of plant phylogeny in influencing their microbiomes is largely lacking. Our main aims was to identify key drivers of plant microbiome assembly. MethodsHere, we conducted a full factorial experiment that included three levels of soil microbial diversity, five plant species from three functional groups (C3, C4, and C3 nitrogen-fixing), and two moisture availability levels. ResultsOur results showed that host identity and plant functional group exerted the strongest effect on leaf microbial assembly, while root and soil microbiomes showed less sensitivity to host selection. The initial soil microbial diversity and community structure significantly impacted soil and root microbial composition, but not leaf microbiomes. Importantly, we observed significant positive linkage between host phylogeny distance and Bray-Curtis dissimilarity index in leaf microbiomes. This finding was further validated through analysis of microbiome data from seven plant species grown across different field and environmental conditions. Interestingly, there was no significant impact of short-term water stress on plant microbial communities. ConclusionsBy providing empirical evidence for important role of host selection in shaping plant microbiomes, this study advances our fundamental knowledge of plant-microbe interactions and their co-evolutionary relationships, and enhances our ability to develop future tools harnessing plant microbiome to improve plant health and productivity.

microbiology↗

bioRxiv2025

A metagenomics-based tool for surveillance of bacterial pathogens in environmental samples

Bacterial pathogens are responsible for millions of human deaths and significant losses in food production annually. Soil acts as a natural reservoir for many critical bacterial pathogens, however, the lack of accurate, high-throughput methods to identify the distribution of bacterial pathogens in soil and other environments greatly limits our ability to develop effective surveillance and disease management strategies and policies. Here, we present MetaPatho, an easy-to-use, rapid, robust, and shotgun metagenomics-based tool for identifying human and plant bacterial pathogens in environmental metagenomes. We first constructed high-quality pathogenic databases for the identification of human and plant bacterial pathogens. In-silico tests and soil spike-in experiments, including pathogen DNA spike-in and cell spike-in tests, were then employed to examine the accuracy and robustness of our tool. The in-silico tests suggested that the tool accurately identified pathogenic sequences, achieving an average accuracy of 97.4%, with a specificity of 98.1% and a sensitivity of 97.2%. Further analyses from soil spike-in experiments showed that the tool accurately detected bacterial pathogens at different concentrations, achieving an average accuracy of 96.3%. Overall, our tools can provide a high-throughput and accurate surveillance of bacterial pathogens in environmental metagenomes, contributing to an effective risk management associated with human and plant diseases.

microbiology↗

bioRxiv2025

Structural basis of Retron-Eco8-mediated anti-phage defense

Retrons represent a novel class of bacterial defense systems that employ reverse transcriptase (RT), non-coding RNA, and effector proteins to counteract phage infections. In this study, we elucidate the molecular mechanism of a retron system, Retron-Eco8. Biochemical experiments reveal that the Retron-Eco8 holocomplex, rather than the effector alone, exhibits double-stranded DNA cleavage activity in an ATP-independent manner, triggering abortive infection and effectively halting phage propagation. Cryo-electron microscopy (cryo-EM) analysis reveals a supramolecular assembly comprising four RT subunits, four msDNA (multicopy single-stranded DNA) molecules, and four OLD (overcoming lysogenization defect) nucleases--a configuration critical for anti-phage defense. Structural comparisons between apo and ATP-Mg2+-bound states demonstrate a local conformational change. Notably, we identify the phage SSB (single-stranded DNA-binding) protein as an activator of Retron-Eco8, and phylogenetic analysis of SSB proteins further elucidates the phage resistance specificity. Collectively, our findings delineate the structural architecture of the Retron-Eco8 defense complex and provide mechanistic insights into retron-mediated bacterial immunity.

biophysics↗

bioRxiv2025

Representational Competition of Spatially and Temporally Overlapped Target and Distractor

Representational competition occurs when a task-relevant target stimulus and a distractor overlap in space and time. Given limited neural resources, it is expected that stronger representations of the distractor will result in weaker representations of the target, leading to poorer behavioral performance. We tested this hypothesis by recording fMRI while participants (n = 27) viewed a compound stimulus consisting of randomly moving dots (the target) superimposed on IAPS affective pictures (the distractor). Each trial lasted [~]12 seconds, during which the moving dots and the IAPS pictures were flickered at 4.29 Hz and 6 Hz, respectively. The task was to detect and report brief episodes of coherent motion in the moving dots. Depending on the emotion category of the IAPS pictures, the trials were classified as pleasant, neutral and unpleasant. Focusing on three ROIs: middle temporal cortex (MT), ventral visual cortex (VVC), as well as the primary visual cortex (V1), we performed MVPA analysis to decode the distractor categories in each ROI, and correlated the decoding accuracy, taken to index the strength of distractor representation, with the accuracy in detecting the episodes of coherent motion. The following results were found: (1) the decoding accuracy was above chance level in all ROIs, and (2) in MT and VVC but not in V1, the higher the decoding accuracy, the worse the behavioral performance. These results suggested that distractor information was represented in V1 as well as in the two motion-processing areas, and in the motion-processing areas, stronger representations of the distractor led to poorer ability to process attended information, leading to worse behavioral performance. The hypothesis was thus supported and trade-offs in the fidelity of stimulus representations prompted by neural competition demonstrated.

neuroscience↗

bioRxiv2025

The serine protease homolog Skanda modulates Toll-Phenoloxidase-mediated immunity in Drosophila

Extracellular serine protease (SP) cascades are central regulators of insect innate immunity. These cascades are negatively controlled by serine protease inhibitors (serpins) and fine-tuned by serine protease homologs (SPHs), which resemble SPs but lack catalytic activity. In Drosophila, a key SP cascade--the Toll-phenoloxidase (PO) pathway--governs both the melanization response and Toll-dependent antimicrobial peptide production. This cascade is triggered by secreted pattern-recognition receptors or microbial proteases and converges on two clip-domain SPs, Persephone and Hayan, which activate the Toll ligand Spatzle via the Spatzle-Processing Enzyme (SPE) and process prophenoloxidases. Here, we characterize the SPH Skanda and uncover its role in the Toll-PO cascade. skanda is genomically clustered with hayan and persephone and is transcriptionally induced upon infection. Skanda is unusual among SPHs, containing a long serine/threonine-rich region, two clip domains, and atypical disulfide bonds. Skanda is unstable and subject to cleavage by Grass. Functional assays show that Skanda dampens activation of Hayan, and to a lesser extent Persephone, within the Toll-PO cascade. Notably, skanda-deficient flies are highly susceptible to Staphylococcus aureus despite displaying normal Toll signaling and cuticular melanization. Moreover, compound mutants lacking two members of the hayan-psh-skanda cluster reveal a hidden contribution of Skanda to Toll activation in the absence of Persephone. Together, our results identify Skanda as a modulatory SPH that fine-tunes Toll pathway activity in concert with Persephone and Hayan.

immunology↗

bioRxiv2025

DAXX governs the silencing of LINE1 during spermatogenesis in mice

The suppression of transposable elements in germline is critical for safeguarding fertility. Here we identify that the DAXX, a potent transcription repressor and an H3.3 chaperone, is indispensable for transposable elements silencing during spermatogenesis. Male mice with conditional knockout of Daxx in germ cells mediated by Ddx4-cre display delayed meiotic progression, deformed and reduced production of sperms, and an age-dependent decline in fertility. The ablation of DAXX results in activation of evolutionarily young LINE1 and ERVs subfamilies. Mechanistically, DAXX interacts with DMAP1 to maintain DNA methylation of LINE1 in meiotic cells. In summary, this study identifies DAXX as a previously unknown regulator of spermatogenesis and demonstrates that it functions as an epigenetic regulator to maintain the silencing the young LINE1 by DNA methylation.

developmental biology↗

bioRxiv2025

Angular Deviation Diffuser: A Transformer-Based Diffusion Model for Efficient Protein Conformational Ensemble Generation

Protein functionality is inherently tied to its structure, with both static and dynamic conformations playing critical roles in defining biological activity. While molecular dynamics (MD) simulations have long been the standard for exploring protein dynamics, they come with high computational costs and limited sampling efficiency. Recent advances in deep learning, such as AlphaFold, have significantly improved static protein structure prediction, yet accurately generating the dynamic ensemble of protein conformations remains a complex challenge. In this study, we present a transformer-based diffusion model that generates diverse conformational ensembles of protein backbones by utilizing angular deviations as data flow. Our model combines a cutting-edge diffusion model with the principles of SE(3) symmetry to enhance both the accuracy and efficiency of conformational sampling. Applied to the Vivid (VVD) Photoreceptor protein system, the generated ensembles closely align with those from MD simulations while covering a broader range of conformational states. This approach offers an improved methodology for capturing protein dynamics, contributing to a more comprehensive understanding of protein structure and function.

bioinformatics↗

bioRxiv2025

A comprehensive comparison on clustering methods for multi-slide spatially resolved transcriptomics data analysis

Spatial transcriptomics (ST) data, by providing spatial information, enables simultaneous analysis of gene expression distributions and their spatial patterns within tissue. Clustering or spatial domain detection represents an essential methodology for ST data, facilitating the exploration of spatial organizations with shared gene expression or histological characteristics. Traditionally, clustering algorithms for ST have focused on individual tissue sections. However, the emergence of numerous contiguous tissue sections derived from the same or similar tissue specimens within or across individuals has led to the development of multi-slide clustering methods. In this study, we assess seven single-slide and three multi-slide clustering methods on two simulated datasets and three real datasets. Additionally, we investigate the effectiveness of pre-processing techniques, including spatial coordinate alignment (for example, PASTE) and gene expression batch effect removal (for example, Harmony), on clustering performance. Our study provides a comprehensive comparison of clustering methods for multi-slide ST data, serving as a practical guide for method selection in various scenarios.

bioinformatics↗

bioRxiv2025

Genomic feature of filled regions of telomere-to-telomere genomes in five model species

T2T genome is a telomere-to-telomere high-quality genome with exceptional accuracy, continuity and integrity. It significantly filled some gaps of chromosome. However, the genomic features unique to the filled regions assembled in the T2T genome across species remain unclear. Here, we collected and compared T2T genomes with their older version from human (Homo sapiens), animal (Mus musculus), and plants (Arabidopsis thaliana, Musa acuminata, and Fragaria vesca). We explored the newly filled regions generated by the T2T genome in comparison to the old one, and focused on: (1) the comparison of their locations, (2) the distribution of genomic features, and (3) gene annotation and gene function for filled regions. Research indicated that the filled regions of the T2T genome ordinarily appear in the centromere and telomere regions, contain a great number of repetitive sequences. The T2T genome revealed the identification of a certain number of newly annotated genes, alongside significant variations in common annotated genes. Interestingly, the genomic features of filled regions exhibit distinct patterns between plants and human/animal. T2T genomes feature analysis serves as a crucial resource for studying pattern characteristics across diverse species and advancing the in-depth development of genomics.

genomics↗

bioRxiv2024

Rhythmic Sampling and Competition of Target and Distractor in a Motion Detection Task

It has been suggested that the visual system samples attended information rhythmically. Does rhythmic sampling also apply to distracting information? How do attended information and distracting information compete temporally for neural representations? We recorded electroencephalography (EEG) from participants who detected instances of coherent motion in a random dot kinematogram (RDK; the target), overlayed on different categories (pleasant, neutral, and unpleasant) of affective images from the International Affective System (IAPS) (the distractor). The moving dots were flickered at 4.29 Hz whereas the IAPS pictures were flickered at 6 Hz. The time course of EEG spectral power at 4.29 Hz was taken to index the temporal dynamics of target processing. The spatial pattern of the EEG spectral power at 6 Hz was similarly extracted and subjected to a moving-window MVPA decoding analysis to index the temporal dynamics of processing pleasant, neutral, or unpleasant distractor pictures. We found that (1) both target processing and distractor processing exhibited rhythmicity at [~]1 Hz and (2) the phase difference between the two rhythmic time courses were related to task performance, i.e., relative phase closer to {pi} predicted a higher rate of coherent motion detection whereas relative phase closer to 0 predicted a lower rate of coherent motion detection. These results suggest that (1) in a target-distractor scenario, both attended and distracting information were sampled rhythmically and (2) the more target sampling and distractor sampling were separated in time within a sampling cycle, the less distraction effects were observed, both at the neural and the behavioral level.

neuroscience↗

bioRxiv2024

Age-related decline of PKA-RIIβ level in SNc dopaminergic neurons underlies PD pathogenesis

The cyclic-AMP dependent protein kinase A (Protein kinase A, PKA) regulates dopaminergic function in the substantia nigra pars compacta (SNc). However, whether PKA is involved in the pathogenesis of Parkinsons disease (PD) is unknown. Here, by collecting and analyzing the current worldwide SNc transcriptomic datasets of PD patients, we found a decline of PKA-RII{beta} subunit level in the SNc of PD patients. The decreased PKA-RII{beta} subunit level was positively correlated with decreased dopamine synthesis and increased oxidative stress in the SNc of PD patients. PKA-RII{beta} subunit is expressed in the striatum and the SNc. PKA-RII{beta} gene knockout mice (RII{beta}-KO) showed a age-related parkinsonism at 12 months of age. Using Cre-LoxP system, we observed that RII{beta} re-expression in the SNc dopaminergic neurons rescued parkinsonism of RII{beta}-KO mice. RII{beta} re-expression in striatal neurons did not affect parkinsonism of RII{beta}-KO mice. The spontaneous parkinsonism could be developed in 12-month-old SNc dopaminergic neuron-specific RII{beta}-deficient mice. Single-nucleus RNA sequencing revealed decreased PKA activity, reduced dopamine synthesis and raised oxidative stress in the SNc dopaminergic neurons of RII{beta}-KO mice. Adeno-associated virus (AAV)-mediated gene therapy targeting PKA-RII{beta} in the SNc dopaminergic neurons rescued parkinsonism in PD mouse model. Taken together, these findings indicate that PKA-RII{beta} may be a key factor of human genetic etiologies of PD. The therapy targeting PKA-RII{beta} in the SNc dopaminergic neurons may be promising for PD treatment.

neuroscience↗

bioRxiv2024

Stimulus repetition induces a two-stage learning process in primary visual cortex

Repeated stimulus exposure alters the brains response to the stimulus. We investigated the underlying neural mechanisms by recording functional MRI data from human observers passively viewing 120 presentations of two Gabor patches (each Gabor repeating 60 times). We evaluated support for two prominent models of stimulus repetition, the fatigue model and the sharpening model. Our results uncovered a two-stage learning process in the primary visual cortex. In Stage 1, univariate BOLD activation in V1 decreased over the first twelve repetitions of the stimuli, replicating the well-known effect of repetition suppression. Applying MVPA decoding along with a moving window approach, we found that (1) the decoding accuracy between the two Gabors decreased from above-chance level ([~]60% to [~]70%) at the beginning of the stage to chance level at the end of the stage ([~]50%). This result, together with the accompanying weight map analysis, suggested that the learning dynamics in Stage 1 were consistent with the predictions of the fatigue model. In Stage 2, univariate BOLD activation for the remaining 48 repetitions of the two stimuli exhibited significant fluctuations but no systematic trend. The MVPA decoding accuracy between the two Gabor patches was at chance level initially and became progressively higher as stimulus repetition continued, rising above and staying above chance level starting at the [~]35th repetition. Thus, results from the second stage supported the notion that sustained and prolonged stimulus repetition prompts sharpened representations. Additional analyses addressed (1) whether the neural patterns within each learning stage remained stable and (2) whether new neural patterns were evoked in Stage 2 relative to Stage 1.

neuroscience↗

bioRxiv2024

The discovery of phages in the Substantia Nigra and its implication for Parkinson's Disease

BackgroundA century ago, a mystery between virus and Parkinsons disease (PD) was described. Owing to the limitation of human brain biopsy and the challenge of electron microscopy in observing virions in human brain tissue, it has been difficult to study the viral etiology of PD. Recent discovery of virobiota reveals that viruses coexist with humans as symbionts. Newly-developed transcriptomic sequencing and novel bioinformatic approaches for mining the encrypted virome in human transcriptome make it possible to study the relationship between symbiotic viruses and PD. Nevertheless, whether viruses exist in the human substantial nigra (SN), and whether symbiotic viruses underlie PD pathogenesis remain unknown. MethodsWe collected current worldwide human SN transcriptomic datasets from the United States, the United Kingdom, the Netherlands and Switzerland. We used bioinformatic approaches including viruSITE and the Virus-Track to identify the existence of viruses in the SN of patients. The comprehensive RNA sequencing-based virome analysis pipeline was used to characterize the virobiota in the SN. The Pearsons correlation analysis was used to examine the association between the viral RNA fragment counts (VRFC) and PD-related human gene sequencing reads in the SN. The differentially expressed genes (DEGs) in the SN between PD patients and non-PD individuals were used to examine the molecular signatures of PD and also evaluate the impact of symbiotic viruses on the SN. FindingsWe observed the existence of viruses in the human SN. A dysbiosis of virobiota was found in the SN of PD patients. A significant correlation between VRFC and PD-related human gene expression was detected in the SN of PD patients. These PD-related human genes correlated to VRFC were named as the virus-correlated PD-related genes (VPGs). We identified three bacteriophages (phages), including the Proteus phage VB_PmiS-Isfahan, the Escherichia phage phiX174 and the Lactobacillus phage Sha1, that might impair the gene expression of neural cells in the SN of PD patients. The Proteus phage VB_PmiS-Isfahan was a common virus in the SN of patients from the UK, the Netherlands, and Switzerland. VPGs and DEGs together highlighted that the phages might dampen dopamine biosynthesis and weaken cGAS-STING function. InterpretationThis is the first study to discover the involvement of phages in PD pathogenesis. A life-long low symbiotic viral load in the SN may be a contributor to PD pathogenesis. Our findings unlocked the black box between brain virobiota and PD, providing a novel insight into PD etiology from the perspective of phages-human symbiosis.

bioinformatics↗

bioRxiv2024

GeneLLM: A Large cfRNA Language Model for Cancer Screening from Raw Reads

We present GeneLLM, a novel large language model that offers a transformative approach to non-invasive cancer detection and biomarker discovery by directly interpreting plasma cell-free RNA (cfRNA) sequences. Unlike traditional annotation-dependent methods, GeneLLM operates without prior knowledge, achieving significantly improved multi-cancer detection accuracy. Critically, GeneLLM identifies novel cfRNAs ( pseudo-biomarkers) originating from previously unannotated genomic regions-overlooked by existing methods-offering new therapeutic targets and insights into intercellular communication. This innovative, cost-effective approach bypasses traditional bioinformatics tools, generating novel pseudo-biomarkers that outperform existing methods even with low-depth sequencing data. Consequently, GeneLLM opens new avenues for biomarker discovery and expands our understanding of the extracellular transcriptomes role in cancer development.

bioinformatics↗