Biology subjects

YANG, Y.

Publications and source records attributed to YANG, Y..

8 recordsLinked to original sources

bioRxiv2025

The Staphylococcus aureus LXG-domain toxins EsxX and SAR0287 do not promote virulence in a zebrafish larval infection model

The Staphylococcus aureus type VIIb secretion system (T7SSb) is a multiprotein secretion system that secretes toxins with antibacterial activity, but which is also required for full virulence in animal models of infection. S. aureus strains carry one of four T7SSb locus types, named essC1 to essC4, each of which encodes a characteristic LXG-family substrate at the T7SS locus. In essC2 strains this LXG-domain protein is EsxX, which has a glycine zipper sequence in its C-terminus and has potent antibacterial membrane-depolarising activity. In this work we recognise conserved features of the essC2 and essC3 systems, identifying the LXG protein SAR0287 as structurally and functionally similar to EsxX. Using a zebrafish larval hindbrain ventricle infection model we demonstrate that the T7SSb of essC2 and essC3 representative strains contribute to bacterial replication and zebrafish mortality. However, there is no significant loss of virulence in the model system if EsxX or SAR0287 are absent. These findings indicate there is no discernible role for either toxin in this virulence model.

microbiology↗

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

Deviant functional connectivity patterns in the EEG and their potential use for dyslexia screening

Developmental dyslexia (DD) is a common learning disorder with potential neural origins. While EEG-based brain activation measures combined with machine learning have shown promise for DD screening, these approaches often lack validation on independent participants, which is a crucial step for practical application. This study developed an EEG-based screening approach and investigated the neural correlates of DD in Chinese children. EEG signals were recorded from 130 children (82 with DD, 48 typically developing) aged betweeen 7 and 11 during resting-state and working memory tasks. The EEG data were preprocessed into clean segments to compute functional connectivity (FC) matrices across four frequency bands (delta, theta, alpha, beta). The segments were split into two independent samples, ensuring independence at the participant level: Sample 1, used for training and five-fold cross validation of the convolutional neural networks, and Sample 2, used for cross-sample validation with the trained model. The beta-band FC index in the eyes-open condition achieved the highest within-sample classification accuracy (98%) and cross-sample accuracy (70%, p < .001). Discriminative FC patterns revealed that children with DD exhibited reduced temporal-parietal and central connectivity but increased frontal-central connectivity, likely reflecting compensatory mechanisms. Within the DD group, stronger FCs showed significant negative correlations with Chinese word reading accuracy and fluency. These findings suggest that EEG-based FC measures can effectively distinguish DD and reveal neural markers associated with impaired reading performance. This approach shows promise for noninvasive screening and deeper insight into the neural basis of DD, particularly in non-alphabetic language systems.

neuroscience↗

bioRxiv2025

RIPK3-dependent sequential recruitment of MLKL and RIPK1 drives PANoptotic cell death and chemokine production

PANoptosis, an immunogenic programmed cell death (PCD) modality, integrates features of pyroptosis, apoptosis, and necroptosis through assembly of the PANoptosome complex. Despite its conceptualization as a distinct PCD form, PANoptosis remains controversial due to insufficient characterization of its morphological hallmarks and molecular regulation. This study aimed to investigate the molecular mechanisms underlying the assembly of PANoptosomes in the PANoptotic pathway. We identified a novel receptor-interacting protein kinase 3 (RIPK3)-initiated PANoptotic pathway that functions without pattern recognition receptors (PRRs) and the ASC (apoptosis-associated speck-like protein containing a CARD) inflammasome. Using multimodal imaging and biochemical approaches, we identify unique morphological signatures distinguishing PANoptotic cells from canonical pyroptotic, apoptotic, or necroptotic counterparts. Mechanistically, RIPK3 forms round homopolymeric scaffolds--distinct from necroptotic amyloid-like fibers--to sequentially recruit MLKL and RIPK1, forming a dynamic RIPK3-MLKL-RIPK1-FADD-caspase-8 complex (RIPK3-PANoptosome). This platform coordinates concurrent activation of pyroptotic, apoptotic, and necroptotic effectors. Cross-regulatory interactions between these pathways establish a homeostatic system where perturbations bias death modality into a certain cell death type, altering the death process and outcomes. Functionally, PANoptotic cells orchestrate chemokine secretion through parallel kinase-dependent (RIPK3-MLKL) and kinase-independent (RIPK1-IKK-NF-{kappa}B) mechanisms, driving macrophage recruitment. Our findings resolve the molecular logic of PANoptosome assembly, redefine PANoptosis as a tunable PCD paradigm, and establish its role in immunomodulation, providing a framework for targeting inflammatory cell death in disease.

cell biology↗

bioRxiv2024

Continuous Prediction of Mice Lever-Pressing Kinematic Parameters by Background Removed Single-photon Calcium Images

Calcium imaging has gained extensive application in neural decoding tasks because of its high precision in observing cortical neural activity. Nevertheless, the immense data volume and complexity of automated signal extraction algorithms in calcium imaging result in significant delays in extracting neuronal calcium fluorescence signals, greatly constraining the efficiency of neural decoding research and its applicability in real-time tasks. Although a few studies have successfully used partial neuronal signals from calcium imaging data for real-time neural decoding and brain-computer interface tasks, they fail to leverage the complete neuronal dataset from experiments, which limits their ability to decode continuous and complex movements. In response to this challenge, we introduce a neural decoding method based on background-removed single-photon calcium images. This approach extracts three-dimensional spatiotemporal representations of neuronal activity via background removal and employs a decoder combining 3D-ResNet and RNN networks to enable continuous and rapid decoding of mouse lever-pressing kinematic parameters. Compared with traditional methods for neural decoding using single-photon calcium imaging, this approach offers higher accuracy and faster speed. Combined with real-time motion correction algorithms, the proposed neural decoding approach meets real-time decoding requirements at a 20Hz acquisition frame rate, achieving single decoding in just 21.8ms. This advancement significantly improves the efficiency of single-photon calcium imaging-based neural decoding, offering solutions for its application in real-time tasks, such as optical brain-computer interfaces.

neuroscience↗

bioRxiv2022

Spatial exploration of immune cell heterogeneity in skin functional scar-less wound regeneration model at single-cell resolution

Inevitable skin scarring devoid of dermal appendages bring about unfavorable effects on both aesthetic and physiological functions. Here we offered an available method for large-area wound regeneration using biodegradable Aligned extracellular matrix (ECM) scaffold. Accelerating wound coverage and enhanced hair follicle (HF) neogenesis were observed with the implantation of biomaterials. Multimodal analysis during wound regeneration provides a unique lens through which we can explore the foreign body responses (FBR) around biomaterials. First, we identified cell heterogeneity in responses to ECM scaffolds using single-cell RNA sequencing. Next the spatial anchor highlighted preferential recruitment of T cells around biomaterials colocalized with hair follicle precursor cells. Reconstruction of signaling pathways suggested the pro-regenerative effect of the adaptive immune systems on HF neogenesis. Immunodeficient mice lacking mature T lymphocytes lost the ability to activate papillary fibroblast as well as stimulate HF regeneration, validating the potential therapeutic effect of the adaptive immune system activated by biomaterials. In conclusion, this study provided the further understanding of the FBR and facilitate the design of immunoregulatory biomaterials for biomedical application in the future.

immunology↗

bioRxiv2020

Dual symbiosis in the deep-sea hydrothermal vent snail Gigantopelta aegis revealed by its hologenome

Animals endemic to deep-sea hydrothermal vents often form obligatory relationships with bacterial symbionts, maintained by intricate host-symbiont interactions. Endosymbiosis with more than one symbiont is uncommon, and most genomic studies focusing on such dual symbiosis systems have not investigated the host and the symbionts to a similar depth simultaneously. Here, we report a novel dual symbiosis among the peltospirid snail Gigantopelta aegis and its two Gammaproteobacteria endosymbionts - one being a sulphur oxidiser and the other a methane oxidiser. We assembled high-quality genomes for all three parties of this holobiont, with a chromosome-level assembly for the snail host (1.15 Gb, N50 = 82 Mb, 15 pseudo-chromosomes). In-depth analyses of these genomes reveal an intimate mutualistic relationship with complementarity in nutrition and metabolic codependency, resulting in a system highly versatile in transportation and utilisation of chemical energy. Moreover, G. aegis has an enhanced immune capability that likely facilitates the possession of more than one type of symbiont. Comparisons with Chrysomallon squamiferum, another chemosymbiotic snail in the same family but only with one sulphur-oxidising endosymbiont, show that the two snails sulphur-oxidising endosymbionts are phylogenetically distant, agreeing with previous results that the two snails have evolved endosymbiosis independently and convergently. Notably, the same capabilities of biosynthesis of specific nutrition lacking in the host genome are shared by the two sulphur-oxidising endosymbionts of the two snail genera, which may be a key criterion in the selection of symbionts by the hosts.

genomics↗

bioRxiv2018

The role of two-component system response regulator BceR in antimicrobial resistance, virulence, biofilm formation, and stress response of group B Streptococcus.

The hypervirulent Group B Streptococcus (Streptococcus agalactiae, GBS) serogroup III clonal cluster 17 has been associated with neonatal GBS invasive disease and meningits. Serogroup III, ST283 has recently been implicated in invasive disease among non-pregnant adults in Asia. These strains cluster with strains from freshwater fishes from aquaculture and a foodborne outbreak of sepsis, especially with septic arthritis, had been linked to such consumption in Singapore in 2015. Through comparative genome analyses of invasive and non-invasive strains of ST283, we identified a truncated response regulator gene in the non-invasive strain. This two component response gene, previously named a DNA binding regulator, is conserved among GBS strains and is a homologue of Bacillus subtilis BceR, the response regulator of the BceRSAB system. Loss of function of the BceR response gene in the invasive GBS strain demonstrated bacitracin susceptibility in{Delta} BceR mutant with MICs of 256-fold and four-fold reduction in bacitracin and human cathelicin LL-37 compared to wild type and complementation strains. Upregulation of dltA of wild type strain vs{Delta} BceR mutant was demonstrated (p<0.0001), and was previously shown in Staphylococcus aureus to resist and repel cationic peptides through excess positive charges with D-alanylation of teichoic acids on the cell wall. In addition,{Delta} BceR mutant was less susceptible under oxidative stress under H2O2 stress when compared to wild type strain (p<0.001) and inhibited biofilm formation (p<0.05 and p < 0.0001 for crystal violet staining and cfu counts). The{Delta} BceR mutant also showed reduced mortality as compared to wild type strain (p<0.01) in a murine infection model. Taken together, BceRS is involved in bacitracin and antimicrobial peptide resistance, survival under oxidative stress, biofilm formation and play an important role in the virulence of GBS.\n\nAuthor SummaryTwo-component systems (TCSs) play an important role in virulence in bacteria, and are involved in detecting environmental changes. Although S. agalactiae was reported to contain more predicted TCSs than Streptococcus pneumoniae, few have been studied in detail. In this work, comparative genomic analysis of GBS invasive (hyper-virulent) and non-invasive serotype III-4 strains were performed to determine any gene differences that may account for severity of disease in humans. BceR-like TCS was selected and suspected to be involved in virulence, and thus BceR was deleted in a hyper-virulent GBS serotype III-4 strain. We demonstrated that this BceR-like TCS is involved in GBS virulence and induced proinflammatory host immune responses. Our study of TCS BceR may guide further research into the role of other TCSs in GBS pathogenicity, and further explore therapeutic targets for GBS disease.

microbiology↗