Biology subjects

Qing, L.

Publications and source records attributed to Qing, L..

8 recordsLinked to original sources

bioRxiv2025

Nuclear polysaccharides maintain H3K9me3-heterochromatin and genomic stability

Polysaccharides are known to be synthesized by enzymes in the endoplasmic reticulum and Golgi apparatus and transported through the secretory pathway to the cell surface or extracellular space1, where they mediate essential biological processes2-6. While classical localization and functions of polysaccharides are well established, their presence and potential roles in the nucleus remain unclear. Here, we demonstrate that N-glycans, a type of polysaccharides, are present in the cell nucleus and modify inner nuclear membrane (INM) proteins across diverse cell types--a modification referred to as N-linked glycosylation (N-glycosylation). N-glycosylation is enriched in chromatin regions marked by H3K9me3 and long interspersed nuclear element-1 (LINE-1) retrotransposons. N-glycosylation inhibition and INM protein N-glycosylation site mutation both downregulate H3K9me3 within lamina-associated domains (LADs) and lead to genomic instability. Mechanistically, N-glycosylation regulates the interaction between the histone H3K9 methyltransferase SETDB1 and INM proteins, promotes the association of SETDB1 with the INM, and maintains H3K9me3. Moreover, we reveal that canonical N-glycan biosynthetic machinery in ER contributes to the N-glycosylation of INM proteins. These findings uncover a previously unrecognized nuclear role for polysaccharides, broadening our understanding beyond their traditional subcellular distributions and functional profiles.

molecular biology↗

bioRxiv2024

Deciphering the Gut Microbiome's Influence on Depression: A Community-Level Constraint-Based Metabolic modelling Approach

BackgroundDepression is a common mental disorder worldwide, and its pathogenesis remains incompletely understood. However, increasing evidence suggests that gut microbiota play a significant role in the development of depression through the gut-brain-microbiota axis. However, due to the substantial individual variability in gut microbiota, while metabolic functions and metabolites between individuals are relatively similar, analyzing functional profiles and metabolic products yields more accurate results. ResultsIn this study, gut microbiota abundance data were collected from 354 depression patients and 5575 healthy individuals in the GMrepo v2 database. After matching for age and BMI, 271 paired samples from each group were retained. Alpha diversity analysis revealed significant differences between the two groups in the Observed, Shannon, and Chao1 indices, while beta diversity analysis indicated only subtle differences in gut microbiota composition. LEfSe analysis identified 23 differential species, with 18 enriched in the healthy group and 5 in the depression group. Further alpha diversity analysis of reaction abundance showed significant differences in the Observed and Chao1 indices, while beta diversity analysis did not reveal significant differences in reaction abundance. Differential and enrichment analyses identified 89 reactions that were significantly different between the groups, which were enriched in 4 metabolic pathways. Wilcoxon signed-rank test of COBRA-predicted metabolic fluxes revealed significant differences in the fluxes of 21 metabolites. Although the abundance of six species did not differ significantly between the two groups, their contributions to metabolic fluxes were significantly different. Mediation analysis indicated that gut microbiota influence the progression of depression by modulating various metabolites. ConclusionsThis study combined species abundance with COBRA metabolic flux predictions and mediation analysis, identified several differential species, as well as multiple differential metabolic fluxes, such as Cu2+ and L-Dopa, which were attributed to species like Dorea. Species such as Acholeplasma and Acidovorax were found to influence the progression of depression by affecting various metabolites, including Cu2+. These findings contribute to a deeper understanding of the relationship between gut microbiota and depression, offering new directions for the diagnosis and treatment of depression.

bioinformatics↗

bioRxiv2024

Mechanism of intestinal microbial metabolic flux disorder in hypertension

Hypertension is a major risk factor for cardiovascular diseases such as stroke and heart failure. Recent studies have shown that changes in the composition and function of the gut microbiota are closely related to the onset and development of hypertension. However, the individual differences in gut microbiota species make it difficult for traditional analysis methods to effectively reveal the pathogenic mechanisms of hypertension. In contrast, the inter-individual variability in gut microbial metabolites is much smaller, allowing for better cross-individual comparisons and reducing confounding factors in analysis. The interactions between gut microbiota and metabolites are highly complex, and network analysis can systematically capture this complexity. In this study Flux Balance Analysis (FBA) was utilized to predict the metabolic flux of gut microbiota and constructed cross-feeding networks. Random Forest and XGBoost models were employed to identify metabolites associated with hypertension. A differential microbial correlation network was used to analyze important metabolically related microbial sub-networks, and ultimately, the metabolic abnormalities and metabolite-related pathways were analyzed at the network level using the metabolite correlation network and cross-feeding networks. It was observed that the interaction patterns among 25 species--collectively referred to as the KEPR guild, with the most abundant genera being Eubacterium, Ruminococcus, Klebsiella, and Parabacteroides--changed, leading to alterations in 12 metabolites, such as choline (chol), 1-butanol (btoh), trimethylamine (tma), cytidine (cytd), and betaine (glyb) etc. Choline can be oxidized to form betaine, thereby affecting host blood pressure. Abnormalities in siroheme and methanethiol may result in reduced secretion of hydrogen sulfide by microbes, which in turn impacts blood pressure regulation mechanisms. The changes in these 12 metabolites may also enhance the degradation of mucin-type O-glycans and reduce butyrate metabolic activity, weakening the protective ability of intestinal epithelial cells. This may lead to inflammation and oxidative stress, exacerbating endothelial cell damage and consequently resulting in endothelial dysfunction and increased blood pressure. The findings of this study provide new insights into the pathogenic mechanisms of hypertension and offer potential targets for clinical intervention.

bioinformatics↗

bioRxiv2024

Systematic Mining of gut microbiota biomarkers for IBD

BackgroundInflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohns disease (CD), represents a chronic inflammatory condition with an incompletely understood etiology. Emerging evidence suggests that alterations in gut microbiota composition play a pivotal role in disease development. Here, we leveraged gut fecal metagenomic data (3044 samples: 2248 IBD and 796 healthy) from publicly available sources to explore microbiome biomarkers related to IBD to provide new ideas for clinical treatment. ResultsOur analyses revealed marked disparities in microbial species abundance and composition between IBD and healthy samples in both male and female subjects from the United States, whereas such distinctions were absent in subjects from Spain. Hierarchical and systematic investigations uncovered microbial phyla, such as Verrucomicrobia and Firmicutes, associated with IBD in US cohorts. Furthermore, we identified 127 highly correlated pathways with these differential microbes, covering functions such as peptidoglycan biosynthesis III, dTDP-L-rhamnose biosynthesis I, starch degradation, and glucose-1-phosphate degradation. Gut microbial metabolites were predicted based on metagenomic data using the MelonnPan workflow and 16 metabolites with significant differences were identified that collectively contribute to energy metabolism, digestion, skin integrity and general bodily function. ConclusionsThis study identified differences in microbial species and metabolic pathways related to Inflammatory Bowel Disease (IBD) through hierarchical and systematic analysis, which can aid in the clinical diagnosis of IBD. Pathways such as Peptidoglycan Biosynthesis III and dTDP-L-Rhamnose Biosynthesis I are associated with the generation of bacterial cell walls, and disruptions in these pathways affect bacterial activity, leading to an imbalance in the hosts gut microbiota. Based on the hypotheses regarding the pathogenesis of IBD derived from the above mining results, it provides a theoretical basis for selecting precise treatment options.

bioinformatics↗

bioRxiv2021

Geminivirus C4 proteins inhibit GA signaling via prevention of NbGAI degradation, to promote viral infection and symptom development in N. benthamiana

Phytohormone gibberellin (GA) is an important plant signaling molecule that regulates plant growth and defense against abiotic and biotic stresses. To date, the molecular mechanism of the plant responses to viral infection mediated by GA is still undetermined. DELLA is a repressor of GA signaling and is recognized by the F-box protein, a component of the SCFSLY1/GID2 complex. The recognized DELLA is degraded by the ubiquitin-26S proteasome, leading to the activation of the GA signaling. Here, we report that ageratum leaf curl Sichuan virus (ALCScV)-infected N. benthamiana plants showed dwarfing symptom and abnormal flower development. The infection of ALCScV alters the expressions of GA pathway-related genes and decreases the content of endogenous GA significantly in N. benthamiana. Further, ALCScV-encoded C4 protein interacts with the DELLA protein NbGAI, and interferes with the interaction between NbGAI and NbGID2 to prevent the degradation of NbGAI, leading to the inhibition of the GA signaling pathway. Silencing of NbGAI or exogenous GA3 treatment significantly reduces viral accumulation and disease symptoms in N. benthamiana plants. The same results were proved by the experiments with C4 protein encoded by tobacco curly shoot virus (TbCSV). Therefore, we propose a novel mechanism of geminivirus C4 proteins controling virus infection and disease symptom development through interfering GA signaling pathway. Author SummaryGibberellins (GAs) are plant hormones that are essential for many developmental processes in plants. It has indicated that plant virus infection can induce abnormal flower development and influence GA pathway resulting the plant dwarfing symptom, but the underlying mechanisms is still not well described. Here, we demonstrate that geminivirus - encoded C4 protein regulates the GA signaling pathway to promote viral accumulation and disease symptom development. Through directly interacting with NbGAI, the C4 protein interferes with the interaction between NbGAI and NbGID2, which inhibits the degradation of NbGAI. As a result, the GA signaling pathway is blocked, and the infected plants display symptoms of typical dwarfing and delayed flowering. Our results reveal a novel mechanism by which geminivirus C4 proteins influence viral pathogenicity via interfering the GA signaling pathway, and provide new insights into the interaction between virus and host.

pathology↗

bioRxiv2021

Portrait of a genus: the genetic diversity of Zea

Maize is a globally valuable commodity and one of the most extensively studied genetic model organisms. However, we know surprisingly little about the extent and potential utility of the genetic variation found in the wild relatives of maize. Here, we characterize a high-density genomic variation map from ~700 genomes encompassing maize and all wild taxa of the genus Zea, identifying over 65 million single nucleotide polymorphisms (SNPs), 8 million Insertion/Deletion (InDel) polymorphisms, and over one thousand novel inversions. The variation map reveals evidence of selection within taxa displaying novel adaptations such as perenniality and regrowth. We focus in detail on evidence of convergent adaptation in highland teosinte and temperate maize. This study not only indicates the key role of hormone related pathways in highland adaptation and flowering time related pathways in high latitude adaptation, but also identifies significant overlap in the genes underlying adaptations to both environments. To show how this data can identify useful genetic variants, we generated and characterized novel mutant alleles for two flowering time candidate genes. This work provides the most extensive sampling to date of the genetic diversity inherent in the genus Zea, resolving questions on evolution and identifying adaptive variants for direct use in modern breeding.

evolutionary biology↗

bioRxiv2021

Novel anti-repression mechanism of H-NS proteins by a phage "early protein".

H-NS family proteins, bacterial xenogeneic silencers, play central roles in genome organization and in the regulation of foreign genes. It is thought that gene repression is directly dependent on the DNA binding modes of H-NS family proteins. These proteins form lateral protofilaments along DNA. Under specific environmental conditions they switch to bridging two DNA duplexes. This switching is a direct effect of environmental conditions on electrostatic interactions between the oppositely charged DNA binding and N-terminal domains of H-NS proteins. The Pseudomonas lytic phage LUZ24 encodes the early protein gp4, which modulates the DNA binding and function of the H-NS family protein MvaT of Pseudomonas aeruginosa. However, the mechanism by which gp4 modulates MvaT activity remains elusive. In this study, we show that gp4 specifically interferes with the formation and stability of the bridged MvaT-DNA complex. Structural investigations suggest that gp4 acts as an "electrostatic zipper" between the oppositely charged domains of MvaT protomers, and stabilizes a structure resembling their "half-open" conformation, resulting in relief of gene silencing and adverse effects on P. aeruginosa growth. The ability to control H-NS conformation and thereby its impact on global gene regulation and growth might open new avenues to fight Pseudomonas multidrug resistance.

biochemistry↗

bioRxiv2020

Transcriptome Profiling of different types of human respiratory tract cells infected by SARS-CoV-2 Highlight an unique Role for Inflammatory and Interferon Response

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) at the end of 2019 has caused a large global outbreak and now become a major public health issue. Lack of data underlying how the human host interacts with SARS-CoV-2 virus. In the current study, We performed Venn-analysis, Gene ontology (GO), KEGG pathway analysis and Protein-protein interaction analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during human respiratory tract cells infected with SARS-CoV-2. We selected four studies through a systematic search of the Gene Expression Omnibus (GEO) database or published article about SARS-CoV-2 infection in different types of respiratory tract cells. We found 36 overlapping upregulated genes among different types of cells after viral infection. Further functional enrichment analysis revealed these DEGs are most likely involved in biological processes related to inflammatory response and response to cytokine, cell component related to extracellular space and I-kappaB/NF-kappaB complex, molecular function related to protein binding and cytokine activity. KEGG pathways analysis highlighted altered conical and casual pathways related to TNF, NF-kappa B, Cytokine-cytokine receptor interaction and IL17 signaling pathways during SARS-CoV-2 infection with CXCL1, CXCL2, CXCL3, CXCL8, CXCL10, IL32, CX3CL1, CCL20, IRF1, NFKB2 and NFKB1A up-regulated which may explain the inflammatory cytokine storms associated with severe cases of COVID-19.

immunology↗