Browsing by Author "He, Bo"

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    Cardiomyocyte glucocorticoid and mineralocorticoid receptors directly and antagonistically regulate heart disease in mice
    (American Association for the Advancement of Science, 2019-04-16) Oakley, Robert H.; Cruz-Topete, Diana; He, Bo; Foley, Julie F.; Myers, Page H.; Xu, Xiaojiang; Gomez-Sanchez, Celso E.; Chambon, Pierre; Willis, Monte S.; Cidlowski, John A.; Medicine, School of Medicine
    Stress is increasingly associated with heart dysfunction and is linked to higher mortality rates in patients with cardiometabolic disease. Glucocorticoids are primary stress hormones that regulate homeostasis through two nuclear receptors, the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), both of which are present in cardiomyocytes. To examine the specific and coordinated roles that these receptors play in mediating the direct effects of stress on the heart, we generated mice with cardiomyocyte-specific deletion of GR (cardioGRKO), MR (cardioMRKO), or both GR and MR (cardioGRMRdKO). The cardioGRKO mice spontaneously developed cardiac hypertrophy and left ventricular systolic dysfunction and died prematurely from heart failure. In contrast, the cardioMRKO mice exhibited normal heart morphology and function. Surprisingly, despite the presence of myocardial stress, the cardioGRMRdKO mice were resistant to the cardiac remodeling, left ventricular dysfunction, and early death observed in the cardioGRKO mice. Gene expression analysis revealed the loss of gene changes associated with impaired Ca2+ handling, increased oxidative stress, and enhanced cell death and the presence of gene changes that limited the hypertrophic response and promoted cardiomyocyte survival in the double knockout hearts. Re-expression of MR in cardioGRMRdKO hearts reversed many of the cardioprotective gene changes and resulted in cardiac failure. These findings reveal a critical role for balanced cardiomyocyte GR and MR stress signaling in cardiovascular health. Therapies that shift stress signaling in the heart to favor more GR and less MR activity may provide an improved approach for treating heart disease.
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    Evaluation of top-down mass spectral identification with homologous protein sequences
    (Biomed Central, 2018-12-28) Li, Ziwei; He, Bo; Kou, Qiang; Wang, Zhe; Wu, Si; Liu, Yunlong; Feng, Weixing; Liu, Xiaowen; Medical and Molecular Genetics, School of Medicine
    BACKGROUND: Top-down mass spectrometry has unique advantages in identifying proteoforms with multiple post-translational modifications and/or unknown alterations. Most software tools in this area search top-down mass spectra against a protein sequence database for proteoform identification. When the species studied in a mass spectrometry experiment lacks its proteome sequence database, a homologous protein sequence database can be used for proteoform identification. The accuracy of homologous protein sequences affects the sensitivity of proteoform identification and the accuracy of mass shift localization. RESULTS: We tested TopPIC, a commonly used software tool for top-down mass spectral identification, on a top-down mass spectrometry data set of Escherichia coli K12 MG1655, and evaluated its performance using an Escherichia coli K12 MG1655 proteome database and a homologous protein database. The number of identified spectra with the homologous database was about half of that with the Escherichia coli K12 MG1655 database. We also tested TopPIC on a top-down mass spectrometry data set of human MCF-7 cells and obtained similar results. CONCLUSIONS: Experimental results demonstrated that TopPIC is capable of identifying many proteoform spectrum matches and localizing unknown alterations using homologous protein sequences containing no more than 2 mutations.
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    Improving alignment accuracy on homopolymer regions for semiconductor-based sequencing technologies
    (BioMed Central, 2016-08-22) Feng, Weixing; Zhao, Sen; Xue, Dingkai; Song, Fengfei; Li, Ziwei; Chao, Duojiao; He, Bo; Hao, Yangyang; Wang, Yadong; Liu, Yunlong; Department of Medical and Molecular Genetics, IU School of Medicine
    BACKGROUND: Ion Torrent and Ion Proton are semiconductor-based sequencing technologies that feature rapid sequencing speed and low upfront and operating costs, thanks to the avoidance of modified nucleotides and optical measurements. Despite of these advantages, however, Ion semiconductor sequencing technologies suffer much reduced sequencing accuracy at the genomic loci with homopolymer repeats of the same nucleotide. Such limitation significantly reduces its efficiency for the biological applications aiming at accurately identifying various genetic variants. RESULTS: In this study, we propose a Bayesian inference-based method that takes the advantage of the signal distributions of the electrical voltages that are measured for all the homopolymers of a fixed length. By cross-referencing the length of homopolymers in the reference genome and the voltage signal distribution derived from the experiment, the proposed integrated model significantly improves the alignment accuracy around the homopolymer regions. CONCLUSIONS: Besides improving alignment accuracy on homopolymer regions for semiconductor-based sequencing technologies with the proposed model, similar strategies can also be used on other high-throughput sequencing technologies that share similar limitations.
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    Lipopolysaccharide treatment induces genome-wide pre-mRNA splicing pattern changes in mouse bone marrow stromal stem cells
    (BioMed Central, 2016-08-22) Zhou, Ao; Li, Meng; He, Bo; Feng, Weixing; Huang, Fei; Xu, Bing; Dunker, A. Keith; Balch, Curt; Li, Baiyan; Liu, Yunlong; Wang, Yue; Department of Medical and Molecular Genetics, IU School of Medicine
    Background Lipopolysaccharide (LPS) is a gram-negative bacterial antigen that triggers a series of cellular responses. LPS pre-conditioning was previously shown to improve the therapeutic efficacy of bone marrow stromal cells/bone-marrow derived mesenchymal stem cells (BMSCs) for repairing ischemic, injured tissue. Results In this study, we systematically evaluated the effects of LPS treatment on genome-wide splicing pattern changes in mouse BMSCs by comparing transcriptome sequencing data from control vs. LPS-treated samples, revealing 197 exons whose BMSC splicing patterns were altered by LPS. Functional analysis of these alternatively spliced genes demonstrated significant enrichment of phosphoproteins, zinc finger proteins, and proteins undergoing acetylation. Additional bioinformatics analysis strongly suggest that LPS-induced alternatively spliced exons could have major effects on protein functions by disrupting key protein functional domains, protein-protein interactions, and post-translational modifications. Conclusion Although it is still to be determined whether such proteome modifications improve BMSC therapeutic efficacy, our comprehensive splicing characterizations provide greater understanding of the intracellular mechanisms that underlie the therapeutic potential of BMSCs. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-2898-5) contains supplementary material, which is available to authorized users.