Biology subjects

Song, C.

Publications and source records attributed to Song, C..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

Spatial Transcriptomics Reveal Developmental Dynamics of the Human Cerebral Cortex and Striatum

The human fetal brain undergoes morphological changes that contribute to the development of regional functionalities. However, the features of structural development, the underlying molecular and cellular signatures in the fetal brain remain unclear. With spatial transcriptomics and snRNA-seq, we identified 25 forebrain regions and characterized the dynamic changes in the cortex and striatum during the late first and early second trimesters. In particular, we discovered that temporal lobe enriched NPY-expressing L2/3 EX neuron potentially interacted with L4 EX neurons during cortical expansion and arealization. Additionally, the gyrus and sulcus were developmental asynchronous, in which HOPX and SPARC genes were potentially involved. Further investigation on the striatum showed specific genes and cell types that enriched in patch and matrix compartments, and SST-positive interneurons potentially involved in the development of these structures. Together, our results give insights into the understanding of early fetal brain development.

bioinformatics↗

bioRxiv2025

A trade-off mechanism underpins the evolution of a young two-gene sex-determining system in plants

Sexual systems in animals and plants are remarkably diverse, with dioecy having evolved independently in numerous lineages. In plants, dioecy often evolved more recently than in the best-studied animal systems, making plants especially important for understanding how separate sexes evolved independently from functionally hermaphrodite ancestors. Despite long-standing theories of developmental trade-offs in sex allocation, the underlying genetic mechanisms remain elusive. Here, we show that the XY sex determination system in the dioecious plant species Eurycorymbus cavaleriei in Sapindaceae involves two Y-linked mutations that act jointly within the developmental male-female trade-off: YUN{Delta}, a truncated allele that lowers the dosage of the D-class MADS-box gene YUN, and SUNMAO, a novel sRNA locus that silences the X-linked SUN allele. In females, SUN stabilizes the HD-ZIP transcription factor KUN, which is a known sex determinant in another dioecious plant, thereby promoting femaleness by increasing YUN expression; loss of SUN expression, together with the effect of YUN{Delta}, shifts development toward males. Two interlocking regulatory loops in this "SKY" module (SUN-KUN-YUN) fine-tunes YUN dosage. This dioecious system in E. cavaleriei likely evolved by sequential mutations in genes acting in the predicted male-female trade-off system, with their close linkage reflecting a translocation, and later recombination-suppressing inversions.

plant biology↗

bioRxiv2025

Label invariance: a guiding principle for ecological models

Ecological models, though diverse in form, are strengthened when they obey guiding principles. We formalize and advocate for a foundational principle we call "label invariance", which says that a models dynamics must remain the same when identical individuals are arbitrarily grouped into distinct sub-populations. This principle is a necessary consequence of trait continuity--the observation that ecological interactions change continuously as organisms become more similar. Violation of label invariance often implies a hidden, intrinsic niche differentiation between species, which may obscure the mechanisms of biodiversity maintenance. We provide a general framework for constructing both deterministic and stochastic models that follow label invariance. We further demonstrate its utility as a complementary, non-statistical tool for empirical model selection. In sum, label invariance provides an important test for evaluating existing ecological models and a guide for developing new ones, promoting clarity in model assumptions from the outset.

ecology↗

bioRxiv2025

Psychedelic 5-HT2A agonist increases spontaneous and evoked 5-Hz oscillations in visual and retrosplenial cortex

Visual perception appears largely stable in time. However, psychophysical studies have revealed that theta waves (4-8 Hz) can modulate perception and have been linked to various cognitive states and functions. Neither the contribution of theta waves to cortical activity nor their impact during aberrant brain states have been resolved at high spatiotemporal scales. Here, using cortex-wide population voltage imaging in awake mice, we found that bouts of 5-Hz oscillations in the visual cortex are accompanied by similar oscillations in the retrosplenial cortex, occurring both spontaneously and evoked by visual stimulation. Injection of psychotropic 5-HT2AR agonist induced a significant increase in spontaneous 5-Hz oscillations, and also increased the power, occurrence probability and temporal persistence of visually evoked 5-Hz oscillations. This modulation of 5-Hz oscillations in both cortical areas indicates a strengthening of top-down control of perception, supporting an underlying mechanism of perceptual filling and visual hallucinations.

neuroscience↗

bioRxiv2025

A critical role of sux cistron-mediated sucrose uptake for virulence of the rice blight pathogen Xanthomonas oryzae pv. oryzae

The virulence of Xanthomonas oryzae pv. oryzae, the causal agent of bacterial blight (BB) of rice, critically depends on the activation of SWEET sucrose uniporters of the host. To date, the role of SWEET-released sucrose for virulence remains unclear. We here identified the sux locus of Xoo, consisting of a LacI-type repressor (SuxR), an outer membrane TonB-like porin (SuxA), an inner membrane MFS H+-symporter (SuxC), and a cytosolic sucrose hydrolase (SuxB). Structural and functional analyses demonstrate that SuxB has exclusive sucrose hydrolase activity. Mutant analyses show that the transporter SuxC and the sucrose hydrolase are necessary for growth of bacteria on sucrose, while SuxA is not essential, likely due to the ability of other porins to transport sucrose across the outer membrane. Consistent with a role of SuxR as a sucrose repressor, transcriptome studies show sucrose-dependent regulation of the suxA/suxB genes. Besides a role of sucrose for reproduction, we found that sucrose promotes motility, EPS production, biofilm formation, and virulence. Notably, the SuxC sucrose H+-symporter and the sucrose hydrolase SuxB were required for full virulence of Xoo on indica and japonica rice varieties. Our findings indicate that pathogen-induced sucrose efflux via SWEETs provides sucrose to Xoo, that Xoo uses the sux gene cluster to acquire and utilize sucrose, and that sucrose promotes bacterial fitness and xylem colonization. Significance StatementUnderstanding disease mechanisms is critical for developing strategies to protect plants against infections. Bacterial blight, a major threat to global rice production, is caused by Xanthomonas oryzae pv. oryzae strains that hijack rice SWEET sucrose uniporters. Xanthomonas oryzae pv. oryzae deploys a set of molecular "keys", TAL effectors, to trigger host sucrose release. Sugars could serve as nutrients for the bacteria or prime host defense. Here, we provide evidence that the pathogens ability to attack and grow depends on sucrose uptake. We explore how crucial virulence functions, such as motility, EPS production, and biofilm formation, depend on the activity of the sucrose utilization system, supporting a key role of sucrose for the nutrition of the bacteria in the xylem.

microbiology↗

bioRxiv2025

Improved Anisotropic Network Models for Membrane Protein Dynamics and Mechanosensitive Ion Channels

Mechanosensitive (MS) ion channels are crucial for translating mechanical stimuli into cellular responses; however, their dynamic properties pose significant challenges for experimental investigations. This study introduces two enhanced Anisotropic Network Models (ANMs) that incorporate Membrane Contact Probability (MCP) to more effectively capture the influence of the cell membrane on protein dynamics. MCP-ANM and MCP-mANM (multiscale ANM) outperform traditional ANM models that do not explicitly consider membranes when predicting the flexibility of various types of membrane proteins. Furthermore, by integrating MCP-mANM with Perturbation Response Scanning (PRS), we are able to effciently simulate the conformational changes of MS proteins subjected to different mechanical forces. This methodology allows for the examination of various gating mechanisms, including force-from-lipids and force-from-tether, across multiple MS ion channels such as NOMPC, MscS, and PIEZO. The calculated mechanosensitivity of the MS channels aligns well with the experimental findings. These results demonstrate the effectiveness of MCP-incorporated ANM in linking mechanical stimuli to protein dynamics, providing a reliable and effcient framework for understanding the mechanotransduction and gating mechanisms of MS ion channels.

biophysics↗

bioRxiv2025

TypeSINE: Genome-Wide Detection of SINE Retrotransposon Polymorphisms Reveals Functional Variants Linked to Body Size Variation in Pigs

The genotyping of Short Interspersed Element (SINE) retrotransposon insertion polymorphisms (RIPs) from large-scale sequencing data remains technically challenging. To overcome this limitation, we developed TypeSINE to genotype SINE-RIPs from short-read sequencing data. Analyzing 362 porcine genomes, we identified 749,835 SINE-RIPs (>85% accuracy), including 65,917 common variants (5-95% frequency). These showed uniform genomic distribution ([~]22/Mb), with 40% in introns. Population analyses based on SINE-RIPs revealed independent domestication of Asian and European pigs from local wild populations, followed by introgression. GWAS detected body size-associated regions using SINE-RIPs. We created pigRIPdb (82,227 curated SINE-RIPs) with browsing and visualization tools. The methods cross-species applicability is supported by conserved SINE evolutionary patterns, enabling polymorphism discovery of SINEs in livestock and humans. TypeSINE represents an efficient, scalable solution for genome-wide SINE-RIP analysis, advancing population genomics research. TeaserAn integrated SINE-RIP genotyping platform with companion database enables large-scale analysis of SINE evolution and population genetics in swine

bioinformatics↗

bioRxiv2025

Mechanism-driven screening of membrane-targeting and pore-forming antimicrobial peptides

The rise of antibiotic resistance has generated an urgent demand for the discovery of new antimicrobial peptides (AMPs), prompting the development of various screening strategies. However, the specific function mechanisms of AMPs are often overlooked during the screening and optimization processes. In this study, we introduce a mechanism-driven screening approach that employs machine learning-based computational models to identify peptide sequences that target membranes and form pores. This approach explicitly considers critical factors such as structural features, membrane ainity, and the ability of peptides to oligomerize. Our method was applied to the metaproteomes of poison frogs, African clawed frogs, and human skin, followed by experimental validation. Seven peptides were successfully screened, each demonstrating antimicrobial activity with minimal hemolysis and cytotoxicity. These peptides exhibited membrane disruption capabilities in liposome leakage assays, with three showing broad-spectrum antimicrobial activity. Furthermore, single-molecule experiments indicated that these peptides can oligomerize on membranes, while electrophysiological measurements detected pore formation, confirming the effectiveness of our screening strategy. Therefore, our screening approach can effectively identify AMP sequences that act through membrane-targeting and poreforming mechanisms, offering a promising, mechanism-driven strategy for the discovery of new antimicrobial agents to combat antibiotic resistance.

biophysics↗

bioRxiv2025

High-Throughput Assessment of Vocal Modulation Following Chemogenetic Inhibition in Songbirds

Chemogenetic tools that enable temporary and repeatable manipulation of neuronal activity have become essential for studying the precise neural underpinning of animal behavior. However, their application has so far been limited to songbirds, which are widely used to study behaviors related to vocal communication. In this study, we applied and evaluated designer receptors exclusively activated by designer drugs (DREADD)-mediated neural suppression in songbirds brains, focusing on its impacts on vocalizations. We found that neuronal activity in zebra finches (Taeniopygia guttata) can be effectively suppressed both in vitro and in vivo using the inhibitory DREADD by its ligand deschloroclozapine (DCZ). By establishing a high-throughput system for recording and analyzing their vocalizations, we systematically assessed the effects of DREADD-mediated suppression on song behavior. Inhibiting HVC in zebra finches led to a reduction in song production number for approximately 90 min and altered phonological features over a longer time course. Notably, the concentration of DCZ required to induce robust effects on song behaviors was higher than doses typically used in mice. Furthermore, suppression of HVC or Area X in Bengalese finches (Lonchura striata domestica) produced a distinct effect on song features, suggesting species-specific responses to chemogenetic intervention. These findings refine the use of chemogenetic tools in songbirds and provide new insights into the neural mechanisms underlying vocal communication.

neuroscience↗

bioRxiv2025

TransAgent: Dynamizing Transcriptional Regulation Analysis via Multi-omics-Aware AI Agent

Transcriptional regulation research, as a core area of life sciences, faces challenges such as scattered multi-omics data, complex joint analysis, and difficulties in integrating data processing tools. To address these issues, we propose TransAgent, an agent software specifically designed for transcriptional regulation analysis. Through innovative designs such as multi-mode operation (planning/execution/automatic), dynamic memory management, rapid MCP tool expansion (integrating over 30 tools), integration of transcriptional regulation annotation data (over 20 data sources including epigenomics and gene expression profiles), and cloud Docker computing, TransAgent significantly improves analysis efficiency. We have successfully applied TransAgent to various transcriptional regulation analysis scenarios such as re-construction of super-enhancer regulatory circuit in esophageal squamous cell carcinoma and identification of key regulators in cardiomyocyte differentiation, demonstrating analytical robustness and uncovering biological insights. TransAgent automates the entire process from raw data processing to advanced analysis, such as joint prediction of multi-omics data, transforming traditionally time-consuming and labor-intensive tasks into a conversation-driven approach. This provides a new paradigm for transcriptional regulation research, centered around large models as the core driver of scalable agent application analysis.

bioinformatics↗

bioRxiv2025

Therapeutic Potential of 20E in Pulmonary Arterial Hypertension: Involvement of Mas Receptor and PI3K/Akt Pathway

BACKGROUND20-Hydroxyecdysone (20E), a natural polyhydroxylated steroid found in various edible plants, exhibits diverse pharmacological effects. This study aims to investigate the preventive and therapeutic effects of 20E on pulmonary arterial hypertension (PAH) and elucidate its underlying molecular mechanisms. METHODSA monocrotaline (MCT)-induced PAH rat model was utilized to evaluate the efficacy of 20E. The Mas receptor antagonist A779 and agonist AVE0991 were used to investigate the role of Mas in PAH progression and 20E-mediated prevention. Molecular docking and pull-down assays were conducted to confirm the interaction between 20E and the Mas receptor. In vitro, the effects of 20E on Ang II-induced proliferation and migration of human pulmonary arterial smooth muscle cells (HPASMCs) were assessed. The PI3K/Akt signaling pathway was analyzed by Western blot. RESULTS20E prevented PAH at 30 mg/kg and 90 mg/kg, while 90 mg/kg rescued pre-existing PAH. The protective effects of 20E were attenuated by A779. 20E upregulated Mas receptor expression and directly bound to it. In vitro, 20E inhibited Ang II-induced HPASMC proliferation and migration. It also downregulated p-PI3K, p-Akt, and p-mTOR while restoring P27 and P21 expression. Furthermore, knockdown of the Mas in HPASMCs abolished the effects of 20E on these processes. CONCLUSIONS20E inhibits PASMC proliferation and migration by activating the Mas receptor and modulating the downstream PI3K/Akt signaling pathway, thereby effectively preventing and rescuing PAH. It may be a promising pharmacological candidate for PAH treatment.

molecular biology↗

bioRxiv2025

Predicting Rhizosphere Competence Related Catabolic Gene Clusters in plant-associated bacteria with RhizoSMASH

Plants release a substantial fraction of their photosynthesized carbon into the rhizosphere as root exudates, a mix of chemically diverse compounds that drive microbiome assembly. Deciphering how plants modulate the composition and activities of rhizosphere microbiota through root exudates is challenging, as no dedicated computational methods exist to systematically identify microbial root exudate catabolic pathways. Here we used and integrated published information on catabolic genes in bacterial taxa that contribute to their rhizosphere competence. We developed the RhizoSMASH algorithm for genome-synteny-based annotation of rhizosphere-competence-related catabolic gene clusters (rCGCs) in bacteria by means of a set of 58 knowledge-based logic detection rules carefully curated through sequence similarity network analysis. Our analysis revealed large heterogeneity of rCGC prevalence both across and within plant-associated bacterial taxa, indicating extensive niche specialization. Furthermore, we validated that the presence or absence of rCGCs in bacterial genomes reflects their catabolic capacity and is predictive for their rhizosphere competence by aligning rhizoSMASH results with paired genome/metabolome datasets of rhizobacterial taxa. RhizoSMASH provides an extensible framework for studying rhizosphere bacterial catabolism, allowing targeted selection of beneficial bacterial taxa for microbiome-assisted breeding approaches for sustainable agriculture.

bioinformatics↗

bioRxiv2025

Lasting effect of psilocybin on sociability can be blocked by DNA methyltransferase inhibition

The recent renaissance in research on psychedelics such as psilocybin has highlighted their therapeutic potential including their lasting influences on brain function. Here we report that a single systemic administration of the serotonergic psychedelic psilocybin can durably promote social behaviour in the Cntnap2-knockout mouse model of autism. This effect can be blocked by pharmacological inhibition of DNA methyltransferase I, indicating an epigenetic mechanism underlying the long-lasting effect of psilocybin.

neuroscience↗

bioRxiv2025

Characterization of an enigmatic tubular ultrastructure in the bacterial defensive symbiont of the Asian citrus psyllid

"Candidatus Profftella armatura" (Betaproteobacteria) is a unique organelle-like defensive symbiont harbored intracellularly within the symbiotic organ of a devastating citrus pest, the Asian citrus psyllid Diaphorina citri (Insecta: Hemiptera). Our previous two-dimensional transmission electron microscopy identified an unprecedented ultrastructure that appeared tubular in Profftella, but their detailed architecture, three-dimensional arrangement, and components were unknown. To address these issues, this study conducted serial block-face scanning electron microscopy, high-voltage electron tomography, and fluorescence in situ hybridization. The results revealed that highly elongated (2.8-136 {micro}m observed), string-shaped Profftella cells contain tubes of various numbers (1-43 per cell observed) and length (up to 45 m observed), depending on the cell length. The tubes were evenly distributed throughout the cells, occupying an average of 6.3% of the total cell volume. Each tube consisted of five or six thin fibers twisted into a right-handed helix, maintaining a consistent diameter of approximately 230 nm along its entire length. Even without fixation or embedding, the tubes retained their shape under high vacuum conditions in electron microscopes, demonstrating their remarkable stability and robustness. These findings suggest that the tubes may help provide mechanical stability to the highly elongated and potentially vulnerable Profftella cells. Further analysis showed that the tubes are closely associated with ribosomes, suggesting a role in protein synthesis. Overall, these results offer new insights into the structural and functional evolution of bacteria, with potential implications for developing novel pest control strategies. Significance statementBacteria generally have simple intracellular structures, lacking organelles. Here, we report a highly elongated, elaborate organelle-like structure with a tubular shape in a bacterial symbiont of an important agricultural pest. The tube, which exhibits high durability and robustness, may contribute to the mechanical stability of the notably elongated symbiont cell. They are closely associated with numerous ribosomes, suggesting a potential role in gene expression. These findings not only enhance our understanding of bacterial evolution but may also provide clues for developing novel strategies for pest control.

microbiology↗

bioRxiv2025

Integrative Analysis of Single-cell and Bulk RNA Sequencing Reveals Macrophage Heterogeneity in Lyme Arthritis

IntroductionLyme arthritis (LA) is a common late-stage manifestation of Lyme disease caused by Borrelia burgdorferi (Bb) infection. Macrophages play a crucial role in LA pathogenesis, yet their heterogeneity and functional states within the arthritic microenvironment remain poorly understood. MethodsWe integrated single-cell RNA sequencing data from ankle joint tissues of Bb-infected C57BL/6 mice with bulk RNA sequencing data from both infected ankle joints and bone marrow-derived macrophages. We developed a LA mouse model and validated key findings through histopathological examination and RT-qPCR analysis. ResultsWe identified nine distinct cell types in the joint microenvironment with significant compositional shifts during disease progression. Analysis of 16,617 Macrophages/Monocytes revealed seven functionally distinct subpopulations with differential responses to infection. Pseudo-time trajectory analysis demonstrated three principal differentiation pathways from monocyte-derived macrophages toward anti-inflammatory, TNF+, and IL1b+ inflammatory phenotypes. Cell-cell communication analysis revealed significantly altered TGF-{beta} signaling networks in LA, with the Tgfb1-(Tglbr1+TgIbr2) axis playing a critical role. GSVA and pathway analyses showed metabolic reprogramming from oxidative phosphorylation toward glycolysis in macrophages during infection. Through integrated analysis and LASSO regression, we identified four characteristic genes (SIRPB1C, FABP5, MMP14, and EGR1) as potential LA biomarkers and developed a diagnostic nomogram with high predictive accuracy. ConclusionOur integrative analysis provides comprehensive insights into macrophage heterogeneity and functional plasticity in LA, identifying characteristic biomarkers and potential therapeutic targets. The metabolic reprogramming and altered TGF-{beta} signaling networks we identified may contribute to disease pathogenesis and offer new avenues for intervention strategies.

genomics↗

bioRxiv2025

Genomic Insights into the Demographic History and Local Adaptation of Wild Boars Across Eurasia

Wild boars exhibit genetic and phenotypic diversity shaped by migrations and local adaptations. Its expansion across Eurasia, especially in central Asia, remains underexplored. Here, we present newly sequenced whole-genome data of 47 wild boars from Eastern Asia, Central Asia, and Europe, combined with 49 existing genomes, creating a comprehensive dataset of 96 individuals. Our analyses show that Asian wild boars and Southeast Asian Suids split [~]3.6 Mya, with Central Asian and Southern Chinese ancestors diverging [~]1.8 Mya. The split between Central Asian and European-Near East ancestors occurred [~]0.9 Mya, followed by a European-Near East divergence [~]0.6 Mya. We identify signatures of local adaptation in Central Asian populations, including two positively selected variants in LPIN1, associated with cold adaptation, and a missense mutation in ALPK2, linked to meat traits. These findings provide insights into wild boar dispersal and adaptation, and shed light on domestic pigs breeding.

evolutionary biology↗

bioRxiv2025

ProtRAP-LM: Fast and accurate protein relative accessibility prediction and membrane protein screening through protein language model embeddings

Membrane proteins play pivotal roles in cellular signaling and transport, making them prime targets for therapeutic intervention. Therefore, expeditious screening and accurate property prediction of these proteins is crucial. Recently, we proposed a new metric, the membrane contact probability (MCP), to characterize the membrane-contacting features of membrane proteins and further refine the prediction of the relative accessibility of proteins (ProtRAP). However, these models relied on evolutionary information in the form of multiple sequence alignments (MSAs), which hindered rapid predictions. In this study, we present a novel transformer-based model, ProtRAP-LM, utilizing language model (LM) embeddings as input features, to quickly and accurately predict MCP and relative accessibility for each residue of a given protein sequence. ProtRAP-LM can achieve accurate predictions for entire proteomes within hours, demonstrating superior performance compared to previous MSA-based models, with a speedup of over 300 times. This empowers us to furnish more thorough annotations of membrane protein sequences on a proteome-wide scale, particularly for single-pass transmembrane proteins, membrane-anchored proteins, and {beta}-sheet-containing membrane proteins, which have long been a challenge in the field. In the end, we provide a comprehensive list of membrane proteins for 48 living organisms, offering a rich resource for investigating the structure and function of these essential biomolecules in the future.

bioinformatics↗

bioRxiv2025

Single-cell spatial transcriptome reveals pathological features of human hippocampus with sclerosis

More than half of epileptic patients ultimately turned to intractable epilepsy. Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), the most common type of intractable epilepsies, whose pathological mechanism remains elusive. Here, using 42 human hippocampal samples from surgical donors of MTLE (32 with and 10 without HS) through single-cell resolution Stereo-seq and histologcial experiments, we revealed spatially pathological changes of gene expression and cell type composition with HS systematically. After precise parcellation of hippocampal subregions and differentially expressed gene (DEG) analysis between each region with and without sclerosis, we found Cornu Ammonis (CA) subregions with higher number of DEGs were vulnerable to sclerosis, especially CA1 and CA3. Within CA1, we found that CA1-superficial and proximal areas were more vulnerable than CA1-deep and distal areas in sclerosis. Meanwhile, after analyzing 350,795 segmented cells from Stereo-seq, we found dramatically increasing density of astrocyte accompanied with significantly decreasing density of excitatory neurons in CA1, especially superficial and proximal CA1, and CA3 in sclerosis. In these two vulnerable subregions, proliferative astrocyte (P_astrocyte) and reactive astrocyte (R_astrocyte) were found to be enriched whereas apoptotic subtype of astrocyte (A_astrocyte), related with apoptotic pathway, was mainly located in alveus, which strengthened cell communication with reactive microglia (R_microglia) in HS, revealing the novel pathological feature in our work. The pseudotime analysis indicated that CA excitatory neurons underwent synaptic impairment, energy dysfunction, aging, and finally losing cell identity until death through autophagy or apoptosis. Besides, we also found a resilient subtype, EX_CA2-4.3, highly expressed extracellular matrix related genes including PDYN, and was increasing the interaction of BDNF-NTRK, NFASC-CNTN1 to withstand the damage from sclerosis. Together, our study provided a reference of human hippocampus with and without HS caused by MTLE, and highlighted the potential pathological mechanism on molecular and cellular level of MTLE-HS.

neuroscience↗