1,721,092 research outputs found
Data Speak How to Treat Disease
No full textSchematic overview of big data-based precision medicine platform.N
E3 ligase BRUTUS Is a Negative Regulator for the Cellular Energy Level and the Expression of Energy Metabolism-Related Genes Encoded by Two Organellar Genomes in Leaf Tissues
No full textE3 ligase BRUTUS (BTS), a putative iron sensor, is expressed in both root and shoot tissues in seedlings of Arabidopsis thaliana. The role of BTS in root tissues has been well established. However, its role in shoot tissues has been scarcely studied. Comparative transcriptome analysis with shoot and root tissues revealed that BTS is involved in regulating energy metabolism by modulating expression of mitochondrial and chloroplast genes in shoot tissues. Moreover, in shoot tissues of bts-1 plants, levels of ADP and ATP and the ratio of ADP/ATP were greatly increased with a concomitant decrease in levels of soluble sugar and starch. The decreased starch level in bts-1 shoot tissues was restored to the level of shoot tissues of wild-type plants upon vanadate treatment. Through this study, we expand the role of BTS to regulation of energy metabolism in the shoot in addition to its role of iron deficiency response in roots
Transcriptional regulatory networks underlying the reprogramming of spermatogonial stem cells to multipotent stem cells
Get PDFSpermatogonial stem cells (SSCs) are germline stem cells located along the basement membrane of seminiferous tubules in testes. Recently, SSCs were shown to be reprogrammed into multipotent SSCs (mSSCs). However, both the key factors and biological networks underlying this reprogramming remain elusive. Here, we present transcriptional regulatory networks (TRNs) that control cellular processes related to the SSC-to-mSSC reprogramming. Previously, we established intermediate SSCs (iSSCs) undergoing the transition to mSSCs and generated gene expression profiles of SSCs, iSSCs and mSSCs. By comparing these profiles, we identified 2643 genes that were up-regulated during the reprogramming process and 15 key transcription factors (TFs) that regulate these genes. Using the TF-target relationships, we developed TRNs describing how these TFs regulate three pluripotency-related processes (cell proliferation, stem cell maintenance and epigenetic regulation) during the reprogramming. The TRNs showed that 4 of the 15 TFs (Oct4/Pou5f1, Cux1, Zfp143 and E2f4) regulated cell proliferation during the early stages of reprogramming, whereas 11 TFs (Oct4/Pou5f1, Foxm1, Cux1, Zfp143, Trp53, E2f4, Esrrb, Nfyb, Nanog, Sox2 and Klf4) regulated the three pluripotency-related processes during the late stages of reprogramming. Our TRNs provide a model for the temporally coordinated transcriptional regulation of pluripotency-related processes during the SSC-to-mSSC reprogramming, which can be further tested in detailed functional studies.111Ysciescopuskc
Statistical Modeling for Enhancing the Discovery Power of Citrullination from Tandem Mass Spectrometry Data
No full textCitrullination is a post-translational modification implicated in various human diseases including rheumatoid arthritis, Alzheimer's disease, multiple sclerosis, and cancers. Due to a relatively low concentration of citrullinated proteins in the total proteome, confident identification of citrullinated proteome is challenging in mass spectrometry (MS)-based proteomic analysis. From these MS-based analyses, MS features that characterize citrullination, such as immonium ions (IMs) and neutral losses (NLs), called diagnostic ions, have been reported. However, there has been a lack of systematic approaches to comprehensively search for diagnostic ions and no statistical methods for the identification of citrullinated proteome based on these diagnostic ions. Here, we present a systematic approach to identify diagnostic IMs, internal ions (INTs), and NLs for citrullination from tandem mass (MS/MS) spectra. Diagnostic INTs mainly consisted of internal fragment ions for di- and tripeptides that contained two and three amino acids with at least one citrullinated arginine, respectively. A statistical logistic regression model was built for a confident assessment of citrullinated peptides that database searches identified (true positives) and prediction of citrullinated peptides that database searches failed to identify (false negatives) using the diagnostic IMs, INTs, and NLs. Applications of our model to complex global proteome data sets demonstrated the increased accuracy in the identification of citrullinated peptides, thereby enhancing the size and functional interpretation of citrullinated proteomes. Copyright © 2020 American Chemical Society.1
BMP4 signaling plays critical roles in self-renewal of R2i mouse embryonic stem cells
No full textMouse embryonic stem cells (mESCs) can be maintained in a pluripotent state under R2i culture conditions that inhibit the TGF-I3 and ERK signaling pathways. BMP4 is another member of the TGF-I3 family that plays a crucial role in maintaining the pluripotency state of mESCs. It has been reported that inhibition of BMP4 caused the death of R2i-grown cells. In this study, we used the loss-of-function approach to investigate the role of BMP4 signaling in mESC self-renewal. Inhibition of this pathway with Noggin and dorsomorphin, two bone morphogenetic protein (BMP) antagonists, elicited a quick death of the R2i-grown cells. We showed that the canonical pathway of BMP4 (BMP/SMAD) was dispensable for self-renewal and maintaining pluripotency of these cells. Transcriptome analysis of the BMPi-treated cells revealed that the p53 signaling and two adhesion (AD) and apoptotic mitochondrial change (MT) pathways could be involved in the cell death of the BMPi-treated cells. According to our results, inhibition of BMP4 signaling caused a decrease in cell adhesion and ECM detachment, which triggered anoikis in the R2i-grown cells. Altogether, these findings demonstrate that endogenous BMP signaling is required for the survival of mESCs under the R2i condition.(c) 2022 Published by Elsevier Inc.N
In vivo post-translational modifications of recombinant mussel adhesive protein in insect cells
No full textMussel adhesive proteins (MAPs) have been suggested as promising bioadhesives for diverse application fields, including medical uses. Previously, we successfully constructed and produced a new type of functional recombinant MAP, fp-151, in a prokaryotic Escherichia coli expression system. Even though the E. coli-derived MAP showed several excellent features, such as high production yield and efficient purification, in vitro enzymatic modification is required to convert tyrosine residues to l-3,4-dihydroxyphenyl alanine (dopa) molecules for its adhesive ability, due to the intrinsic inability of E. coli to undergo post-translational modification. In this work, we produced a soluble recombinant MAP in insect Sf9 cells, which are widely used as an effective and convenient eukaryotic expression system for eukaryotic foreign proteins. Importantly, we found that insect-derived MAP contained converted dopa residues by in vivo post-translational modification. In addition, insect-derived MAP also had other post-translational modifications including phosphorylation of serine and hydroxylation of proline that originally occurred in some natural MAPs. To our knowledge, this is the first report on in vivo post-translational modifications of MAP containing dopa and other modified amino acid residues. (C) 2011 American Institute of Chemical Engineers Biotechnol. Prog., 27: 1390-1396, 2011X111515sciescopu
Novel Online Three-Dimensional Separation Expands the Detectable Functional Landscape of Cellular Phosphoproteome
No full textProtein phosphorylation is a prevalent post-translational modification that regulates essentially every aspect of cellular processes. Currently, liquid chromatography-tandem mass spectrometry (LC-MS/MS) with an extensive offline sample fractionation and a phosphopeptide enrichment method is a best practice for deep phosphoproteome profiling, but balancing throughput and profiling depth remains a practical challenge. We present an online three-dimensional separation method for ultradeep phosphoproteome profiling that combines an online two-dimensional liquid chromatography separation and an additional gas-phase separation. This method identified over 100,000 phosphopeptides (>60,000 phosphosites) in HeLa cells during 1.5 days of data acquisition, and the largest HeLa cell phosphoproteome significantly expanded the detectable functional landscape of cellular phosphoproteome.N
ORESARA 15, a PLATZ transcription factor, controls root meristem size through auxin and cytokinin signalling-related pathways
No full textAn optimal size of post-embryonic root apical meristem (RAM) is achieved by a balance between cell division and differentiation. Despite extensive research, molecular mechanisms underlying the coordination of cell division and differentiation are still fragmentary. Here, we report that ORESARA 15 (ORE15), an Arabidopsis PLANT A/T-RICH SEQUENCE-AND ZINC-BINDING PROTEIN (PLATZ) transcription factor preferentially expressed in the RAM, determines RAM size. Primary root length, RAM size, cell division rate, and stem cell niche activity were reduced in an ore15 loss-of-function mutant but enhanced in an activation-tagged line overexpressing ORE15, compared with wild type. ORE15 forms mutually positive and negative feedback loops with auxin and cytokinin signalling, respectively. Collectively, our findings imply that ORE15 controls RAM size by mediating the antagonistic interaction between auxin and cytokinin signalling-related pathways. A regulatory network involving transcription factor ORE15, auxin, and cytokinin controls cell division and differentiation in the root apical meristem, which affects its size.N
Clioquinol as an inhibitor of JmjC-histone demethylase exhibits common and unique histone methylome and transcriptome between clioquinol and hypoxia
No full textClioquinol (CQ) is a hypoxic mimicker to activate hypoxia-inducible factor-1α (HIF-1α) by inhibiting HIF-1α specific asparaginyl hypoxylase (FIH-1). The structural similarity of the Jumonji C (JmjC) domain between FIH-1 and JmjC domain-containing histone lysine demethylases (JmjC-KDMs) led us to investigate whether CQ could inhibit the catalytic activities of JmjC-KDMs. Herein, we showed that CQ inhibits KDM4A/C, KDM5A/B, and KDM6B and affects H3K4me3, H3K9me3, and H3K27me3 marks, respectively. An integrative analysis of the histone methylome and transcriptome data revealed that CQ-mediated JmjC-KDM inhibition altered the transcription of target genes through differential combinations of KDMs and transcription factors. Notably, functional enrichment of target genes showed that CQ and hypoxia commonly affected the response to hypoxia, VEGF signaling, and glycolysis, whereas CQ uniquely altered apoptosis/autophagy and cytoskeleton/extracellular matrix organization. Our results suggest that CQ can be used as a JmjC-KDM inhibitor, HIF-α activator, and an alternative therapeutic agent in hypoxia-based diseases
TEMPI: Probabilistic modeling Time-Evolving differential PPI networks with MultiPle Information
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