Biology subjects

Yang, J.

Publications and source records attributed to Yang, J..

At least 307 records · Page 17Linked to original sources

bioRxiv2025

Experimental transmission of African swine fever virus by Ornithodoros lahorensis (Acari: Argasidae)

African swine fever (ASF) is an acute, highly contagious infectious disease that affects both domestic and wild pigs, caused by the African swine fever virus (ASFV). ASFV is the only known DNA virus transmitted by arthropod vectors, with acute infection in pigs leading to morbidity and mortality rates as high as 100%.The virus can persist in a transmission cycle among wild boars, soft ticks, and domestic pigs. To date, nine Ornithodoros spp. have been confirmed to be capable of transmitting ASFV worldwide. However, the potential soft tick species capable of transmitting ASFV in China remain unclear. In this study, we compared the ability of Argasidae spp. Ornithodoros lahorensis and Argas persicus, as well as Ixodidae spp., Haemaphysalis longicornis, Rhipicephalus sanguineus and Dermacentor silvarum, to transmit ASFV via animal transmission experiments. The results revealed that O. lahorensis soft ticks, but not A. persicus or Ixodes, could act as competent vectors through transstadial and transovarial transmission of ASFV. The virus titers horizontally transmitted ASFV to ticks were 105.83, 106.59 and 104.31, HAD50/ml respectively. These viruses were detected in the nymphs developed from larvae, adults developed from nymphs, and larvae hatched from eggs by adults. Thus, O. lahorensis ticks are likely an important natural vectors of ASFV, although both mammalian and tick hosts are likely required for the maintenance of ASFV in the sylvatic cycle.

microbiology↗

bioRxiv2025

clusIBD: Robust Detection of Identity-by-descent (IBD) Segments Using Unphased Genetic Data from Poor-quality DNA Samples

Inferring relatedness through the detection of identity-by-descent (IBD) segments is widely used in many fields. However, existing methods are often powerless for poor-quality DNA samples. Here, we propose a method, clusIBD, which can robustly detect IBD segments using unphased genetic data with high genotype errors. We evaluated and compared the performance of clusIBD with IBIS, TRUFFLE, and IBDseq using simulated data, artificial poor-quality materials and ancient DNA samples. The results showed that clusIBD outperformed these state-of-the-art existing tools and may be a promising tool for kinship inference in fields such as ancient DNA analysis and criminal investigation (freely available at https://github.com/Ryan620/clusIBD/).

genetics↗

bioRxiv2025

Precise, Specific, and Sensitive De Novo Antibody Design Across Multiple Cases

The precision design of antibodies, which naturally recognize diverse molecules through six variable loops, remains a critical challenge in therapeutic molecule discovery. In this study, we demonstrate that precise, sensitive, and specific antibody design can be achieved without prior antibody information across eight distinct target proteins. For each target, binders were identified from a yeast display scFv library of approximately 106 sequences, constructed by combining 102 designed light chain sequences with 104 designed heavy chain sequences. Binders with varying binding strengths were identified for all eight targets, including a case where no experimentally resolved target protein structure was available, demonstrating the highest level of precision compared to previous de novo antibody design reports. To further validate the designed antibodies, they were characterized in the IgG format for five distinct targets. The antibodies exhibited favorable developability properties, positioning them as promising hit or lead candidates. Notably, for one target in particular, the IgG-formatted antibodies exhibited affinity, activity, and developability, comparable to a commercial antibody, highlighting the sensitivity of the design method. Furthermore, binders capable of distinguishing closely related protein subtypes or mutants were identified, demonstrating that the method can achieve high molecular specificity. Cryo-EM analysis experimentally validated the designs accuracy by confirming that the key binding interactions were precisely as designed. These findings underscore the effectiveness of precision molecular design based on atomic-accuracy structure prediction. This study establishes computational antibody design as a viable approach for generating therapeutic molecules with tailored properties, with promising potential for achieving the efficacy and safety required for successful therapeutics.

bioengineering↗

bioRxiv2025

Ultrasound Directly Activates Sparse Neurons and Modulates Visual Circuits in Deafened Mice

Focused ultrasound neuromodulation (FUN) is widely regarded as a next-generation technology for neural modulation, with applications spanning rodents, non-human primates, and humans. While mechanistic studies are advancing, a persistent confound--auditory interference--casts doubt on whether ultrasound exerts direct mechanical effects or merely indirect auditory responses. To resolve this, we engineered a circular ultrasound transducer compatible with two-photon calcium imaging and examined its effects on the primary visual cortex (V1) of surgically deafened mice, eliminating auditory contributions. Our results reveal that ultrasound directly activates a sparse subset of ultrasound-sensitive neurons (USSN) (response rate >30%) in V1, comprising only a small fraction of the total population and exhibiting a spatially sparse distribution. The proportion of USSN scale with ultrasound pressure, confirming a direct neuromodulatory effect independent of audition. Intriguingly, despite this sparse activation, ultrasound significantly modulates V1 circuitry: it alters the dynamics of light-sensitive neurons (LSN), with subsets showing excitation, inhibition, or no change in response to visual stimuli. These findings provide the first rigorous in-vivo evidence that FUN induces direct mechanical effects on neural activity, disentangling them from auditory confounds. By demonstrating both the specificity and broader circuit-level impact of ultrasound in deafened mice, this study reframes our understanding of FUNs mechanisms and strengthens its potential as a precise neuromodulatory tool. HighlightsO_LIUltrasound directly activates sparse neurons in deafened mice, demonstrating auditory-independent effects. C_LIO_LISparse ultrasound-sensitive neurons in V1 show pressure-dependent responses. C_LIO_LIUltrasound modulates visual circuitry, with diverse excitatory and inhibitory effects. C_LI

neuroscience↗

bioRxiv2025

The hollow truth: ethylene-triggered ROS, PCD, senescence, and autophagy drive hollow stem formation

Hollow stems have independently evolved multiple times across the plant kingdom, and play crucial roles in plant development and various environmental adaptations. However, the mechanisms underlying stem hollowness remain poorly understood. Water spinach (Ipomoea aquatica) is one of the few hollow-stemmed plants in the Convolvulaceae family, and its hollow stems are essential for thriving in aquatic environments. Using histochemical staining and transcriptome analysis, we identified programmed cell death (PCD) is involved in cavity formation of water spinach shoot tips. Single-cell transcriptome analysis further revealed that ethylene and reactive oxygen species (ROS) drive and regulate this process by activating transcription factors IaNAC074, IaNAC087, IaNAC029, IaNTL9, and IaTGA9, which initiate PCD, senescence, and autophagy, collectively controlling cell death. These findings were validated through treatments with ethylene and ROS reagents in water spinach and transient expression in tobacco. Additionally, transcriptomic data suggest that these mechanisms may also play a role in hollow stem formation in bamboo, highlighting the conservation of PCD regulatory mechanisms in plant development. This work not only fills a major knowledge gap in the adaptive mechanisms of hollow stem formation but also opens new avenues for agricultural and ecological applications, offering strategies to enhance crop tolerance to flooding and accelerate crop growth.

plant biology↗

bioRxiv2025

Chromosome-level genome assemblies of five Sinocyclocheilus species

Sinocyclocheilus, a genus of tetraploid fishes, is endemic to the karst regions of Southwest China. All species within this genus are classified as second-class national protected species due to their unique and fragile habitat. However, absence of high-quality genomic resources has hindered various research efforts to elucidate their phylogenetic relationships and the origin of polyploidy. To address these academic challenges, we at first constructed a high-quality genome assembly for the most abundant representative, golden-line barbel (Sinocyclocheilus grahami), by integration of PacBio long-read and Hi-C sequencing technologies. The final scaffold-level genome assembly of S. grahami is 1.6 Gb in length, with a scaffold N50 up to 30.7 Mb. A total of 42,205 protein-coding genes were annotated. Subsequently, 93.1% of the assembled genome sequences (about 1.5 Gb) and 93.8% of the total predicted genes were successfully anchored onto 48 chromosomes. Furthermore, we obtained chromosome-level genome assemblies for four other Sinocyclocheilus species (including S. anophthalmus, S. maitianheensis, S. anshuiensis, and S. rhinocerous) based on homologous comparison. These genomic data we present in this study provide valuable genetic resources for in-depth investigation on cave adaptation and improvement of economic values and conservation of diverse Sinocyclocheilus fishes.

genomics↗

bioRxiv2025

CaMKKβ regulates transcription factor Elf2 gene methylation to maintain endothelial junctional barrier integrity

The expression of endothelial-enriched receptor tyrosine kinase Tie2 and vascular endothelial cadherin VE-cadherin in endothelial cells (EC) is essential for maintaining endothelial barrier integrity and vascular homeostasis. The Ets family of transcription factors plays a critical role in regulating the expression of Tie2 and VE-cadherin in EC. However, the transcriptional regulation of these factors remains poorly understood. In this study, we performed whole genome methylation analysis and found that the gene encoding the Ets family transcription factor Elf2/Nerf2 was hypermethylated in Camkk{beta}-deficient (Camkk{beta}-/-) mice. Notably, these mice exhibited significantly reduced mRNA and protein levels of Elf2, Tie2, and VE-cadherin, along with uncontrolled lung vascular injury following LPS challenge. Additionally, either depletion of CaMKK{beta} in human lung microvascular endothelial cells or EC-specific deletion of Camkk{beta} in mice led to a decrease in the expression of Elf2, Tie2, and VE-cadherin. Furthermore, administration of the DNA methyltransferase inhibitor 5-azacytidine (5-AZA) or EC-specific expression of wild-type CaMKK{beta} but not the kinase-defective mutant restored the expression of Elf2, Tie2, and VE-cadherin in Camkk{beta}-/-mice. We find that under baseline conditions, methyl CpG binding protein MeCP2 repressed Elf2 expression in EC. Importantly, in EC-restricted Elf2 knockout mice (Elf21EC), lung endothelial barrier integrity was compromised due to dramatically reduced levels of Tie2 and VE-cadherin. Together, these findings underscore the crucial role of CaMKK{beta} in regulating endothelial junctional barrier integrity by controlling Elf2 expression.

cell biology↗

bioRxiv2025

Investigating E3 ubiquitin ligase activity of ORF150 in fish herpesvirus pathogenesis

Fish herpesviruses, members of the family Alloherpesviridae, infect aquatic species. The hosts ubiquitin-proteasome system (UPS) serves as the major intracellular pathway for protein degradation and plays a crucial role in the viral replication cycle. Viruses exploit the UPS to facilitate their replication and evade host immune responses. This study demonstrated that cyprinid herpesvirus 2 (CyHV-2) infection significantly activates the host UPS pathway, as revealed by transcriptomics sequencing analysis. Further, treatment with MG132, a proteasome inhibitor, markedly downregulates intracellular viral replication and gene transcription. Additionally, we identified a novel, highly conserved E3 ubiquitin ligase with a C3HC4-type really interesting gene (RING)-finger (RING-HC) domain, encoded by open reading frame 150 (ORF150) of CyHV-2. These findings provide critical molecular evidence that the host UPS is essential for fish herpesvirus replication and suggest that viral E3 ligases may serve as potential targets for new antiviral strategies.

microbiology↗

bioRxiv2025

Inertial interface cavitation creates complex, flow-like structures within a soft solid

BackgroundInertial cavitation near soft material interfaces generates highly asymmetric bubble dynamics, intense stress localization, and complex fluid-structure interactions. However, the subsurface deformation fields within soft solids remain poorly resolved due to limitations in ultrafast, full-field measurement techniques. ObjectiveThis study aims to quantify the spatiotemporal deformation of soft hydrogels during laser-induced inertial cavitation near a gel-water interface. MethodsWe integrate single-pulse laser-induced inertial cavitation, an embedded internal Digital Image Correlation (DIC) speckle patterning method, and DIC to resolve in situ, full-field subsurface kinematics at 1-2 million frames per second. ResultsAmong all the tested different non-dimensional stand-off distances, four distinct cavitation-interface interaction regimes are identified, spanning symmetric bulk-like oscillations to strongly asymmetric collapses accompanied by interface indentation, jet reversal, and bubble penetration. Full-field measurements reveal stagnation points, vortex-like deformation patterns, and large localized strains that depend on the non-dimensional bubble stand-off distance. ConclusionsThis work establishes an experimental framework for quantifying inertial cavitation dynamics near a compliant gel-water interface. Using ultrafast imaging and DIC, we captured full-field deformation, strain localization, and jet formation across a wide range of stand-off distances near gel-water interfaces.

bioengineering↗

bioRxiv2025

Microglia regulate neuronal activity via structural remodeling of astrocytes

Neuron-glia interactions play a central role in regulating synaptic transmission and neuronal excitability. Structural plasticity of astrocytes is associated with numerous physiological and pathological conditions, however, the mechanism underlying this process remains unknown. To examine the basis for structural astrocyte plasticity, we used the classic example of the loss of astrocytic processes that takes place in the hypothalamic magnocellular system during chronic high-salt intake. We discovered that a high-salt diet triggers a local accumulation of reactive microglia around vasopressin-secreting neurons, but not in other brain areas. Microglia phagocytose astrocytic processes, reducing astrocytic coverage of vasopressin neurons. The pruning of astrocytic processes impairs synaptic glutamate clearance, enabling activation of extrasynaptic glutamate NMDA receptors and increasing the activity of vasopressin neurons. Inhibiting microglia-mediated astrocyte pruning attenuates the increased neuronal activity and vasopressin-dependent hypertensive phenotype of rats fed high-salt diet. Thus, microglia orchestrate neuron-glia interactions and regulate neuronal activity through astrocyte pruning.

neuroscience↗

bioRxiv2025

Structure-based analysis unveils co-origin of LPOR and nitrogenase-like proteins

Structures of nitrogenases, dark-operative protochlorophyllide oxidoreductases, and light-dependent protochlorophyllide oxidoreductases (LPOR) have been resolved. However, their evolutionary relatedness remains elusive. Here, we show, through structural alignment, that all subunits of nitrogenase-like proteins originated from a co-ancestral archaic one-subdomain precursor. LPOR evolved from the BchX/BchY subunits of nitrogenase-like chlorophyllide a oxidoreductase (COR), and the intermediary retinol dehydrogenase through possible genetic recombination. We thus establish previously unknown structural links among key enzymes involved in biological nitrogen-fixation (BNF) and photosynthesis, unraveling structure-guided functional evolution from a single-subunit iron protein to multi-subunit nitrogenase-like COR, and to the single-subunit LPOR for phototrophic metabolism via bacteriochlorophyll, retinal, and chlorophyll. This work also demonstrates structural similarities are imperative for inferring distant origins of functionally divergent proteins, particularly those lacking primary amino-acid sequence identity. Moreover, our findings coupled with AI may be exploited to design innovative light-driven CORs and/or light-utilizing nitrogenases with enhanced efficacy of photosynthesis and BNF. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/634645v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@9f9a2aorg.highwire.dtl.DTLVardef@4243ecorg.highwire.dtl.DTLVardef@796b4corg.highwire.dtl.DTLVardef@17373da_HPS_FORMAT_FIGEXP M_FIG C_FIG Video abstracthttps://www.youtube.com/watch?v=b0qBE1JMaH0 HighlightsO_LILPOR evolves from BchX and BchY subunits of the nitrogenase-like protein (NGLP) COR C_LIO_LIAll subunits of NGLPs can be traced back to the ancestral one-subdomain precursor C_LIO_LIRetinol dehydrogenase acts as a crucial intermediate in the COR to LPOR evolution C_LIO_LIStructure-based design of LUN is showcased to revolutionize protein engineering C_LI

evolutionary biology↗

bioRxiv2025

Centrosome-assisted assembly of the Balbiani body

The Balbiani body (Bb), which was discovered about 170 years ago, is a membraneless organelle in the oocyte in most species. In organisms like Xenopus and Zebrafish, Bb accumulates mitochondria, endoplasmic reticulum (ER), and germline determinants and regulates the proper localization of germline determinants. The Bb forms around the centrosome in the oocyte during early oogenesis. The mechanism behind its assembly has gained attention only very recently. Here, we report that overexpression of the germ plasm matrix protein Xvelo leads to the formation of a Bb-like structure in somatic cells. The Bb-like structure assembles around the centrosome and selectively recruits mitochondria, ER, and germline determinants. Taking advantage of this system, we investigated the roles of centrosome components on the assembly of Xvelo. Our results reveal that multiple components of the centrosome, including Sas6, Cenexin, and DZIP1, interact with Xvelo and promote its assembly, with Sas6 exhibiting the most prominent activity. Importantly, knocking down Sas6, Cenexin, and DZIP1 individually or in combination resulted in reduced Xvelo aggregates. Taken together, our work suggests that the centrosome may function as a nucleation center to promote the initiation of Xvelo assembly, resulting in the formation of the Bb around the centrosome.

cell biology↗

bioRxiv2025

Multi-omic Characterization of HIV Effects at Single Cell Level across Human Brain Regions

HIV infection exerts profound and long-lasting neurodegenerative effects on the central nervous system (CNS) that can persist despite antiretroviral therapy (ART). Here, we used single-nucleus multiome sequencing to map the transcriptomic and epigenetic landscapes of postmortem human brains from 13 healthy individuals and 20 individuals with HIV who have a history of treatment with ART. Our study spanned three distinct regions--the prefrontal cortex, insular cortex, and ventral striatum--enabling a comprehensive exploration of region-specific and cross-regional perturbations. We found widespread and persistent HIV-associated transcriptional and epigenetic alterations across multiple cell types. Detailed analyses of microglia revealed state changes marked by immune activation and metabolic dysregulation, while integrative multiomic profiling of astrocytes identified multiple subpopulations, including a reactive subpopulation unique to HIV-infected brains. These findings suggest that cells from people with HIV exhibit molecular shifts that may underlie ongoing neuroinflammation and CNS dysfunction. Furthermore, cell-cell communication analyses uncovered dysregulated and pro-inflammatory interactions among glial populations, underscoring the multifaceted and enduring impact of HIV on the brain milieu. Collectively, our comprehensive atlas of HIV-associated brain changes reveals distinct glial cell states with signatures of pro-inflammatory signaling and metabolic dysregulation, providing a framework for developing targeted therapies for HIV-associated neurological dysfunction.

bioinformatics↗

bioRxiv2025

Cell signaling pathways discovery from multi-modal data

Deciphering cell signaling pathways is key to understanding biology, disease mechanisms, and developing new therapies. Although advances in multi-omics technologies provide richer insight into signaling, the data remain high-dimensional, heterogeneous, and difficult to interpret, and current computational tools for inferring signaling pathways are limited. To address this, we developed Incytr, a method for efficient discovery of cell signaling pathways through integration of diverse data modalities, including transcriptomics, ATAC-seq, proteomics, phosphoproteomics, and kinomics. We demonstrate its application in COVID-19, Alzheimers disease, and cancer, where it successfully recovers known pathways and generates novel, cell-type-specific hypotheses supported by multiple data types. We further show how integrating Incytr-derived pathways with biomarker and drug databases can support target and drug discovery. Finally, we show that using Incytr-derived signaling pathways as training data for simple natural language processing models can deepen our understanding of cell-cell communication and immune cell dynamics, while helping identify new therapeutic targets.

bioinformatics↗

bioRxiv2025

Principled PCA separates signal from noise in omics count data

Principal component analysis (PCA) is indispensable for processing high-throughput omics datasets, as it can extract meaningful biological variability while minimizing the influence of noise. However, the suitability of PCA is contingent on appropriate normalization and transformation of count data, and accurate selection of the number of principal components; improper choices can result in the loss of biological information or corruption of the signal due to excessive noise. Typical approaches to these challenges rely on heuristics that lack theoretical foundations. In this work, we present Biwhitened PCA (BiPCA), a theoretically grounded framework for rank estimation and data denoising across a wide range of omics modalities. BiPCA overcomes a fundamental difficulty with handling count noise in omics data by adaptively rescaling the rows and columns - a rigorous procedure that standardizes the noise variances across both dimensions. Through simulations and analysis of over 100 datasets spanning seven omics modalities, we demonstrate that BiPCA reliably recovers the data rank and enhances the biological interpretability of count data. In particular, BiPCA enhances marker gene expression, preserves cell neighborhoods, and mitigates batch effects. Our results establish BiPCA as a robust and versatile framework for high-throughput count data analysis.

bioinformatics↗

bioRxiv2025

Generating Correlated Data for Omics Simulation

Simulation of realistic omics data is a key input for benchmarking studies that help users obtain optimal computational pipelines. Omics data involves large numbers of measured features on each samples and these measures are generally correlated with each other. However, simulation too often ignores these correlations, perhaps due to the inconvenience and computational hurdles of doing so. To alleviate this, we describe in detail three approaches for quickly generating omics-scale data with correlated measures which mimic real data sets. These approaches all are based on a Gaussian copula approach with a covariance matrix that decomposes into a diagonal part and a low-rank part. We use these approaches to demonstrate the importance of including correlation in two benchmarking applications. First, we show that variance of results from the popular DESeq2 method increases when dependence is included. Second, we demonstrate that CYCLOPS, a method for inferring circadian time of collection from transcriptomics, improves in performance when given gene-gene dependencies in some circumstances. We provide an R package, dependentsimr, that has efficient implementations of these methods and can generate dependent data with arbitrary distributions, including discrete (binary, ordered categorical, Poisson, negative binomial), continuous (normal), or with an empirical distribution.

bioinformatics↗

bioRxiv2025

Radiation exposure induced blood-brain barrier injury via mitochondria-mediated sterile inflammation

Radiation-induced brain injury (RIBI) is caused by exposure to high doses of ionizing radiation and characterized by severe cognitive dysfunction and brain necrosis. The widespread application of radiotherapy and rapid development of deep space exploration have substantially increased the risk of RIBI. However, the pathogenesis of RIBI is not fully understood, and no effective intervention is available. This work described a blood-brain barrier (BBB) microphysiological system (MPS), that allowed to explore the responses of BBB and distinct brain cells to radiation exposure. This BBB MPS can recapitulate the interface structure and function of BBB in brain microenvironment, including brain endothelial cells, astrocytes, pericytes and microglia co-cultured under flow condition. Following acute exposure to radiation of X-ray or {gamma}-ray, characteristic RIBI-associated pathological responses were observed, including BBB compromise, DNA breaks, inhibited cell proliferation, cell hypertrophy and pro-inflammatory cytokine release. Among the distinctive types of cells, brain endothelial cells showed the highest radiosensitivity as compared to other cells in the MPS. Intriguingly, X-ray and {gamma}-ray radiation consistently induced prominent sterile inflammation responses, especially type I interferon response, in the BBB MPS. These responses were mediated by radiation-induced mitochondrial DNA release and subsequent activation of cGAS-STING signaling pathway. Furthermore, we found abrocitinib (JAK1 inhibitor) and idebenone (mitochondrial protectant) can attenuate radiation-induced inflammation and ameliorate BBB injury. These findings revealed the involvement of mitochondria-mediated inflammation in RIBI pathogenesis, identifying mitochondria as a potential target for new radioprotective measures.

neuroscience↗

bioRxiv2025

Advancing Microbial Comparative Genomics Through Tumor-Normal Inspired Framework

Comparative genomics has emerged as a pivotal methodology for elucidating genetic variations in microbial studies. However, conventional analytical approaches for diploid and polyploid microorganisms have demonstrated limited efficacy in discriminating new mutations from background heterozygosity. This study presents an innovative microbial comparative genomics framework adapted from tumor-normal sequencing methodology. Our approach establishes the original strain as the "normal sample" and the derived strain as the "tumor sample", enabling precise identification of new mutations ("somatic variants") while filtering pre-existing heterozygous sites ("germline variations"). The analytical pipeline also includes assessment of loss-of-heterozygosity (LOH) events and genome-wide detection of copy number variations (CNVs) with resolution to identify both regional CNV and whole-chromosome aneuploidy through integrated CNV and variant allele frequency analysis. We validated this framework using diploid Saccharomyces cerevisiae strains before successfully extending its application to Kluyveromyces marxianus, Candida spp., and Hortaea werneckii, encompassing haploid, diploid, polyploid, and aneuploid states. The methodology revealed previously undetected variations across experimental evolution studies, demonstrating superior resolution compared to conventional approaches. This adaptable platform establishes a new paradigm for microbial genome studies, particularly for organisms with diploid or polyploid states where traditional comparative genomics methods prove inadequate.

microbiology↗