Biology subjects

Wang, j.

Publications and source records attributed to Wang, j..

8 recordsLinked to original sources

bioRxiv2026

Exploring genetic, expression and regulatory patterns of parental alleles in Muscovy duck (Cairina moschata) using haplotype-resolved assemblies

BackgroundAlthough the biological mechanism for heterosis has been debated for a long time, heterosis is widely utilized to increase the global productivity of crops and livestock. Recently, the mechanism has been well characterized in crops and livestock with a male-heterogametic XY system due to genomic assembly advancements, especially the availability of haploid genomes. However, the biological mechanism for heterosis remains unclear in poultry possessing the female-heterogametic ZW system. ResultsHere, we assembled chromosome-level diploid and haploid genomes of the Muscovy duck. We developed an efficient and cost-effective method to assemble 12 variation graph-haploid Muscovy duck genomes from three full-sibling pairs with high quality using short-read Illumina sequences. We further characterized genetic, expression and regulatory patterns of parental alleles at multiple scales. We found that maternal haploid genomes generally had more open chromatin organization and higher accessibility, and higher levels of gene expression, while showing similar DNA methylation levels when compared to paternal haploid genomes. In contrast, the female paternal Z chromosome showed the most, and the male paternal Z chromosome presented more, relaxed chromatin organization and chromatin accessibility, and gene expression compared to the male maternal Z chromosome. Thus, the ZW system largely relies on compensation and balance to regulate gene expression on the sex Z chromosome. Moreover, we identified non-Mendelian regions covering 0.26% of the genome ([~]3.18 Mb). These regions contained lower gene density, GC content, and repeat sequence frequency, but were enriched for DNA motifs bound by transcription factors, likely leading to a compacted chromatin structure and lower chromatin accessibility. ConclusionsOur work here provides a comprehensive profile of parental alleles genetic, expression and regulatory patterns in the female-heterogametic ZW system, and might be useful for the utilization of heterosis in poultry.

genomics↗

bioRxiv2026

Exercise-Induced Epoxy-Eicosanoids Promote Cardiomyocyte Proliferation and Post-Infarction Repair via NR4A1

BACKGROUNDMyocardial infarction (MI) causes irreversible cardiomyocyte loss that exceeds the adult hearts regenerative capacity, leading to adverse remodeling and heart failure. While exercise provides cardiovascular protection, the mechanisms underlying exercise-induced cardiac repair remain unclear. METHODSPlasma levels of free fatty acids and polyunsaturated fatty acid metabolites were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RNA sequencing was performed to identify differentially expressed genes and enriched pathways. NR4A1 was knocked down in mice via tail vein injection of AAV9 carrying shRNA targeting NR4A1 (AAV9-shNR4A1). The role of 17,18-EEQ was evaluated by continuous subcutaneous infusion via osmotic minipump; the involvement of the cAMP-PKA-CREB axis was assessed using specific pharmacological inhibitor. Molecular analyses included ELISA, immunofluorescence staining, QPCR, and western blotting. Additionally, clinical samples were collected from 36 endurance-trained athletes and 30 sedentary individuals (age 18-22, male) for comparative analysis. RESULTSHere we demonstrate that preventive aerobic training promotes post-MI cardiomyocyte proliferation and confers cardioprotection by reducing fibrosis area and improving cardiac function. Targeted lipidomics revealed that exercise elevates circulating epoxyeicosatetraenoic acids (EEQs), particularly 17,18-EEQ; osmotic pump delivery of 17,18-EEQ mimicked the protective effects of exercise, reducing infarct burden and enhancing proliferation markers (Ki67, pH3, Aurora B). Transcriptomic analysis identified NR4A1 as the most prominent up-regulated mRNA under exercise induction; AAV9-mediated NR4A1 knockdown abolished exercise-mediated cardioprotection and proliferative benefits, establishing NR4A1 as essential for exercise-driven repair. Phosphoproteomic profiling revealed that 17,18-EEQ activates the PKA-CREB pathway to induce NR4A1 expression; pharmacological inhibition of adenylyl cyclase, PKA, or CREB phosphorylation reversed EEQ-mediated cardioprotection and proliferation, confirming pathway necessity. Dietary supplementation with eicosapentaenoic acid (EPA), the metabolic precursor of 17,18-EEQ, amplified exercise-induced cardioprotection by enhancing EEQ biosynthesis. CONCLUSIONOur study identifies 17,18-EEQ as an exercise-derived exerkine that promotes cardiomyocyte proliferation and post-MI repair through a PKA-CREB-NR4A1 signaling axis, advancing our understanding of exercise cardioprotection and myocardial regeneration mechanisms while providing novel therapeutic targets for cardiac intervention. What IS New?O_LIAerobic exercise enhances post-myocardial infarction cardiac repair by upregulating the cardio-protective lipid mediator 17,18-EEQ and its downstream effector NR4A1. C_LIO_LI17,18-EEQ promotes cardiomyocyte proliferation and cardiac repair through activation of the cAMP-PKA-NR4A1 signaling axis. C_LIO_LICombining aerobic exercise with omega-3 fatty acid supplementation synergistically improves cardiac remodeling and functional recovery after ischemic injury. C_LI What Are the Clinical Implications?O_LITargeting endogenous cardiomyocyte proliferation represents a promising therapeutic strategy for cardiac regeneration after ischemic injury. C_LIO_LIDietary supplementation with omega-3 fatty acids may be a clinically feasible approach to amplify exercise-induced cardioprotection and improve outcomes after myocardial infarction. C_LI

physiology↗

bioRxiv2025

TRIO-AI: Hybrid temporal graph, ODE, and VAE modeling for high-resolution cellular trajectory inference in liver injury

Resolving dynamic cellular transitions at single-cell resolution is essential for understanding complex biological processes in development, disease, and regeneration. However, existing trajectory inference methods struggle to capture heterogeneous temporal dynamics, particularly for rare or transitional cell populations critical to injury and repair responses. Here, we present TRIO-AI, a hybrid computational framework that synergistically integrates three complementary approaches: Temporal Graph Neural Networks (Temporal GNN) for branching detection, Neural Ordinary Differential Equations (Neural ODEs) for continuous state flow modeling, and Time-Variational Autoencoders (Time-VAE) for density-based transitional state identification. We applied TRIO-AI to single-cell RNA sequencing data from mouse liver ischemia-reperfusion (IR) injury across multiple timepoints (days 0, 1, 3, and 5 post-injury), comprehensively characterizing major hepatic macrophage populations. TRIO-AI identified a distinct transitional macrophage population (MPs_3) that peaks at 48 hours post-injury and exhibits coordinated signatures for lipid handling (LRP1, LRP6, ABCA1, LDLR, SCARB1), efferocytosis (MARCO, MERTK, MSR1), and extracellular matrix engagement (ITGA9, ITGB1, SDC2). This population serves as a critical integrator of multicellular pro-reparative signals through APOE-LRP1 and FN1-ITGA9 signaling axes. Spatial transcriptomics validation confirmed MPs_3 localization to peri-necrotic borders with dramatic enrichment of APOE-LRP1 co-localization at 48 hours (19 pairs) compared to 24 hours (3 pairs). Comparative analysis against five state-of-the-art methods demonstrated TRIO-AIs superior performance in detecting transitional states, accurately reconstructing branching trajectories, and identifying off-path populations missed by conventional approaches. This framework provides a powerful platform for dissecting cellular dynamics in complex biological systems and reveals new insights into macrophage-mediated tissue repair mechanisms.

bioinformatics↗

bioRxiv2024

Urea amidolyase as the enzyme for urea utilization in algae: functional display in Chlamydomonas reinhardtii and evolution in algae

Urea is a crucial nitrogen nutrient source for algae with the potential to stimulate harmful algal blooms, but the molecular machinery underpinning urea uptake and assimilation by algae is not fully understood. Urease (URE) is commonly regarded as the responsible enzyme, but the urea amidolyase (UAD) system, albeit known to exist, has hardly been studied. Here, the phylogenetic distribution, expression patterns, and functional roles of UAD system are examined, which comprises subunits DUR1, DUR2, and DUR3. We find a widespread occurrence of UAD, spanning four major phytoplankton lineages, and potentially independent evolution of URE and lineage-specific loss. Besides, a stronger regulation of UAD by environmental nitrogen concentrations compared to URE is uncovered in both global ocean and local dinoflagellate-dominant bloom events. CRISPR-based mutation in Chlamydomonas reinhardtii shows that subunit DUR2 is essential for urea utilization. DUR2 inactivation led to completely growth restriction and upregulation of DUR1 and DUR3A, suggesting its functional interaction with them. In contrast, DUR3B inactivation only partially halted urea uptake and cell growth but significantly reduced gene expression across the entire UAD system. These findings not only reveal the crucial role of DUR2 in urea utilization in C. reinhardtii and potentially in many other algae, but also suggest DUR2 to be a more suitable indicator of urea utilization than urease, and underscore the importance to consider both URE and UAD enzyme systems when urea utilization by algae is assessed.

ecology↗

bioRxiv2024

Comparative genomics illuminates adaptive evolution of DVNP with lifestyle and with loss of histone H1 in dinoflagellates

About ten years ago dinoflagellate/viral nucleoprotein (DVNP) was discovered in dinoflagellates, an ecologically important and evolutionarily enigmatic group of aquatic protists. Apparently acquired from a viral origin, the appearance of DVNP coincided with the loss of nucleosome, a rare event in eukaryote evolution. Despite the potential importance of DVNP as the substitute of histones, its evolutionary trajectory and adaptive significance remain elusive. Here, we conducted comparative analyses using existing dinoflagellate genomes and transcriptomes from 26 species ranging from ancestral to later-diverging lineages to investigate the pattern of sequence and structural divergence. Results showed that the functional domestication of DVNP in ancestral dinoflagellates coincided with the loss of histone H1, while subsequent DVNP differentiation was accompanied by the yet another genomic innovation: acquisition of bacterial-originated histone-like protein. Furthermore, our data split DVNP into two major groups: the core DVNP that resembles histone H1 and shows consistently high levels of expression and the non-core DVNP with higher sequence variability and showing lower yet variable levels of expression. In addition, we observed a trend in DVNP evolution tracing that in lifestyle differentiation. This work offers insights into the adaptive evolution of DVNP, laying the foundation for further inquiries of evolutionary drivers and functional innovation of DVNP to enhance our understanding of dinoflagellate evolution and ecological success.

microbiology↗

bioRxiv2020

The Arabidopsis demethylase ROS1 cis-regulates defense genes by erasing DNA methylation at promoter-regulatory regions

Active DNA demethylation has emerged as an important regulatory process of plant and mammalian immunity. However, very little is known about the mechanisms by which active demethylation controls transcriptional immune reprogramming and disease resistance. Here, we first show that the Arabidopsis active demethylase ROS1 promotes basal resistance towards Pseudomonas syringae by antagonizing RNA-directed DNA methylation (RdDM). Furthermore, we found that ROS1 facilitates the flagellin-triggered induction of the disease resistance gene RMG1 by limiting RdDM at the 3 boundary of a remnant RC/Helitron transposable element (TE) embedded in its promoter. We further identify flagellin-responsive ROS1 putative primary targets, and show that at a subset of promoters, ROS1 erases methylation at discrete regions exhibiting WRKY transcription factors (TFs) binding. In particular, we demonstrate that ROS1 removes methylation at the orphan immune receptor RLP43 promoter, to ensure DNA binding of WRKY TFs. Finally, we show that ROS1-directed demethylation of the RMG1 and RLP43 promoters is causal for both flagellin responsiveness of these genes and for basal resistance. Overall, these findings significantly advance our understanding of how active demethylases shape transcriptional immune reprogramming to enable antibacterial resistance. HIGHLIGHTSO_LIThe TNL RMG1 that is regulated by ROS1 positively regulates basal resistance towards Pto DC3000 C_LIO_LIROS1 regulates the flg22-triggered differential expression of more than 2000 thousands genes, among which 10% are demethylated by ROS1 C_LIO_LIROS1 facilitates the transcriptional activation of a subset of flg22-induced genes by antagonizing RdDM at discrete promoter regions C_LIO_LIWRKY transcription factors (TFs) bind to the demethylated promoter regions of a subset of flg22-induced ROS1 targets C_LIO_LIThe hypermethylation at the RLP43 promoter, caused by the lack of ROS1, repels DNA binding of two PAMP-responsive WRKY TFs C_LIO_LISpecific hypermethylation at the ROS1-targeted promoter regions of RMG1 and RLP43 is causal for their silencing as well as for disease susceptibility against Pto DC3000 C_LI

genomics↗

bioRxiv2019

Improved Modeling of Peptide-Protein Binding through Global Docking and Accelerated Molecular Dynamics Simulations

Peptides mediate up to 40% of known protein-protein interactions in higher eukaryotes and play a key role in cellular signaling, protein trafficking, immunology and oncology. However, it is challenging to predict peptide-protein binding with conventional computational modeling approaches, due to slow dynamics and high peptide flexibility. Here, we present a prototype of the approach which combines global peptide docking using ClusPro PeptiDock and all-atom enhanced simulations using Gaussian accelerated molecular dynamics (GaMD). For three distinct model peptides, the lowest backbone root-mean-square deviations (RMSDs) of their bound conformations relative to X-ray structures obtained from PeptiDock were 3.3 [A] - 4.8 [A], being medium quality predictions according to the Critical Assessment of PRediction of Interactions (CAPRI) criteria. GaMD simulations refined the peptide-protein complex structures with significantly reduced peptide backbone RMSDs of 0.6 [A] - 2.7 [A], yielding two high quality (sub-angstrom) and one medium quality models. Furthermore, the GaMD simulations identified important low-energy conformational states and revealed the mechanism of peptide binding to the target proteins. Therefore, PeptiDock+GaMD is a promising approach for exploring peptide-protein interactions.

biophysics↗

bioRxiv2019

G-Protein-Coupled Receptor-Membrane Interactions Depend on the Receptor Activation state

G-protein-coupled receptors (GPCRs) are the largest family of human membrane proteins and serve as primary targets of [~]1/3 of currently marketed drugs. In particular, adenosine A1 receptor (A1AR) is an important therapeutic target for treating cardiac ischemia-reperfusion injuries, neuropathic pain and renal diseases. As a prototypical GPCR, the A1AR is located within a phospholipid membrane bilayer and transmits cellular signals by changing between different conformational states. It is important to elucidate the lipid-protein interactions in order to understand the functional mechanism of GPCRs. Here, all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method were performed on both the inactive (antagonist bound) and active (agonist and G protein bound) A1AR, which was embedded in a 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) lipid bilayer. In the GaMD simulations, the membrane lipids played a key role in stabilizing different conformational states of the A1AR. Our simulations further identified important regions of the receptor that interacted distinctly with the lipids in highly correlated manner. Activation of the A1AR led to differential dynamics in the upper and lower leaflets of the lipid bilayer. In summary, GaMD enhanced simulations have revealed strongly coupled dynamics of the GPCR and lipids that depend on the receptor activation state.

biophysics↗