Biology subjects

Ji, B.

Publications and source records attributed to Ji, B..

24 records · Page 2Linked to original sources

bioRxiv2019

Stress-induced myonectin improves glucose homeostasis by inhibiting glycemic response to HPA axis

Inhibiting glycemic response to HPA axis contributes to glycemic control for diabetic patients. Here, mice were subjected to high-fat diet and intermittent chronic stress, and glucose homeostasis and lipolysis were determined during the intervention. Firstly, we found that glucose intolerance appears at the earliest, followed by reduced insulin sensitivity and increased epinephrine (EPI) sensitivity in the early stage of diet-induced obesity. Next we investigated whether chronic stress impairs glycemic control and which mediates its effects. Short-term stress training raises serum and skeletal muscle myonectin (Myn) levels and improves glucose intolerance. Stress attenuates blood glucose and glycerol responses to EPI, but enhances lipolytic response to EPI in adipose tissues. Myn overexpression in vivo improves glucose tolerance and enhances insulin sensitivity at the cost of blunting glycemic responses to EPI. Myn knockdown reduces beneficial effects of stress or exercise on glucose homeostasis. Together, myonectin is a stress-induced myokine that readjusts glycemic and metabolic responses to HPA axis, and thus prevent the progression of glucose intolerance and obesity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/838003v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@42b09forg.highwire.dtl.DTLVardef@59a744org.highwire.dtl.DTLVardef@1f4a01dorg.highwire.dtl.DTLVardef@13bda27_HPS_FORMAT_FIGEXP M_FIG C_FIG One Sentence SummaryChronic stress breaks glucose intolerance cycle to resist diet-induced obesity, through myonectin-mediated inhibition of glycemic response to epinephrine (EPI) and activation of insulin signaling in adipose tissues. HighlightsO_LIEPI sensitivity increases after glucose intolerance and with reduced insulin sensitivity in diet-induced obesity C_LIO_LIChronic stress blunts glycemic responses to EPI and increases myonectin levels in serum and skeletal muscle C_LIO_LIMyonectin attenuates glycemic response to EPI and improves metabolic profile in HFD-fed mice C_LIO_LIReducing myonectin reverses beneficial effects of stress on glucose homeostasis C_LI

physiology↗

bioRxiv2019

Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals

Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.

systems biology↗

bioRxiv2019

Reconstruction and Analysis of a Kluyveromyces marxianus Genome-scale Metabolic Model

BackgroundKluyveromyces marxianus is a thermotolerant yeast with multiple biotechnological potentials for industrial applications, which can metabolize a broad range of carbon sources, including less conventional sugars like lactose, xylose, arabinose and inulin. These phenotypic traits are sustained even up to 45{degrees}C, what makes it a relevant candidate for industrial biotechnology applications, such as ethanol production. It is therefore of much interest to get more insight into the metabolism of this yeast. Recent studies suggested, that thermotolerance is achieved by reducing the number of growth-determining proteins or suppressing oxidative phosphorylation. Here we aimed to find related factors contributing to the thermotolerance of K. marxianus.\n\nResultsHere, we reported the first genome-scale metabolic model of Kluyveromyces marxianus, iSM996, using a publicly available Kluyveromyces lactis model as template. The model was manually curated and refined to include missing species-specific metabolic capabilities. The iSM996 model includes 1913 reactions, associated with 996 genes and 1531 metabolites. It performed well to predict the carbon source utilization and growth rates under different growth conditions. Moreover, the model was coupled with transcriptomics data and used to perform simulations at various growth temperatures.\n\nConclusionsK. marxianus iSM996 represents a well-annotated metabolic model of thermotolerant yeast, which provide new insight into theoretical metabolic profiles at different temperatures of K. marxianus. This could accelerate the integrative analysis of multi-omics data, leading to model-driven strain design and improvement.

systems biology↗

bioRxiv2018

Tissue-specific trans regulation of the mouse epigenome

Although a variety of writers, readers, and erasers of epigenetic modifications are known, we have little information about the underlying regulatory systems controlling the establishment and maintenance of the epigenetic landscape, which varies greatly among cell types. Here, we have explored how natural genetic variation impacts the epigenome in mice. Studying levels of H3K4me3, a histone modification at sites such as promoters, enhancers, and recombination hotspots, we found tissue-specific trans-regulation of H3K4me3 levels in four highly diverse cell types: male germ cells, embryonic stem (ES) cells, hepatocytes and cardiomyocytes. To identify the genetic loci involved, we measured H3K4me3 levels in male germ cells in a mapping population of 60 BXD recombinant inbred lines, identifying extensive trans-regulation primarily controlled by six major histone quantitative trait loci (hQTL). These chromatin regulatory loci act dominantly to suppress H3K4me3, which at hotspots reduces the likelihood of subsequent DNA double-strand breaks. QTL locations do not correspond with enzyme known to metabolize chromatin features. Instead their locations match clusters of zinc finger genes, making these possible candidates that explain the dominant suppression of H3K4me3. Collectively, these data describe an extensive, tissue-specific set of chromatin regulatory loci that control functionally related chromatin sites.

genomics↗

bioRxiv2017

The Tandem Duplicator Phenotype is a prevalent genome-wide cancer configuration driven by distinct gene mutations

The tandem duplicator phenotype (TDP) is a genome-wide instability configuration primarily observed in breast, ovarian and endometrial carcinomas. Here, we stratify TDP tumors by classifying their tandem duplications (TDs) into three span intervals, with modal values of 11 Kb, 231 Kb, and 1.7 Mb. TDPs with prominent ~11 Kb TDs feature the conjoint loss of TP53 and BRCA1. TDPs with ~231 Kb and ~1.7 Mb TDs associate with CCNE1 pathway activation or CDK12 disruptions, in conjunction with TP53 mutations. We prove the driver role of TP53 and BRCA1 abrogation for TDP induction by generating short-span TDP mammary tumors in genetically modified mouse models harboring deleterious mutations in only these two genes. Lastly, heterogeneous combinations of mutations mediated by TDs are selected for and contribute to the oncogenic burden of TDP tumors.

genomics↗

bioRxiv2017

Epistatic networks jointly influence phenotypes related to metabolic disease and gene expression in Diversity Outbred mice

Genetic studies of multidimensional phenotypes can potentially link genetic variation, gene expression, and physiological data to create multi-scale models of complex traits. Multi-parent populations provide a resource for developing methods to understand these relationships. In this study, we simultaneously modeled body composition, serum biomarkers, and liver transcript abundances from 474 Diversity Outbred mice. This population contained both sexes and two dietary cohorts. Using weighted gene co-expression network analysis (WGCNA), we summarized transcript data into functional modules which we then used as summary phenotypes representing enriched biological processes. These module phenotypes were jointly analyzed with body composition and serum biomarkers in a combined analysis of pleiotropy and epistasis (CAPE), which inferred networks of epistatic interactions between quantitative trait loci that affect one or more traits. This network frequently mapped interactions between alleles of different ancestries, providing evidence of both genetic synergy and redundancy between haplotypes. Furthermore, a number of loci interacted with sex and diet to yield sex-specific genetic effects. We were also able to identify alleles that potentially protect individuals from the effects of a high-fat diet. Although the epistatic interactions explained small amounts of trait variance, the combination of directional interactions, allelic specificity, and high genomic resolution provided context to generate hypotheses for the roles of specific genes in complex traits. Our approach moves beyond the cataloging of single loci to infer genetic networks that map genetic etiology by simultaneously modeling all phenotypes.

genetics↗