dbOGAP - An Integrated Bioinformatics Resource for Protein O-GlcNAcylation

<p>Abstract</p> <p>Background</p> <p>Protein O-GlcNAcylation (or O-GlcNAc-ylation) is an O-linked glycosylation involving the transfer of β-<it>N</it>-acetylglucosamine to the hydroxyl group of serine or threonine residues of proteins. Growing evidences suggest that protein O-GlcNAcylation is common and is analogous to phosphorylation in modulating broad ranges of biological processes. However, compared to phosphorylation, the amount of protein O-GlcNAcylation data is relatively limited and its annotation in databases is scarce. Furthermore, a bioinformatics resource for O-GlcNAcylation is lacking, and an O-GlcNAcylation site prediction tool is much needed.</p> <p>Description</p> <p>We developed a database of O-GlcNAcylated proteins and sites, dbOGAP, primarily based on literature published since O-GlcNAcylation was first described in 1984. The database currently contains ~800 proteins with experimental O-GlcNAcylation information, of which ~61% are of humans, and 172 proteins have a total of ~400 O-GlcNAcylation sites identified. The O-GlcNAcylated proteins are primarily nucleocytoplasmic, including membrane- and non-membrane bounded organelle-associated proteins. The known O-GlcNAcylated proteins exert a broad range of functions including transcriptional regulation, macromolecular complex assembly, intracellular transport, translation, and regulation of cell growth or death. The database also contains ~365 potential O-GlcNAcylated proteins inferred from known O-GlcNAcylated orthologs. Additional annotations, including other protein posttranslational modifications, biological pathways and disease information are integrated into the database. We developed an O-GlcNAcylation site prediction system, OGlcNAcScan, based on Support Vector Machine and trained using protein sequences with known O-GlcNAcylation sites from dbOGAP. The site prediction system achieved an area under ROC curve of 74.3% in five-fold cross-validation. The dbOGAP website was developed to allow for performing search and query on O-GlcNAcylated proteins and associated literature, as well as for browsing by gene names, organisms or pathways, and downloading of the database. Also available from the website, the OGlcNAcScan tool presents a list of predicted O-GlcNAcylation sites for given protein sequences.</p> <p>Conclusions</p> <p>dbOGAP is the first public bioinformatics resource to allow systematic access to the O-GlcNAcylated proteins, and related functional information and bibliography, as well as to an O-GlcNAcylation site prediction tool. The resource will facilitate research on O-GlcNAcylation and its proteomic identification.</p

GSK3 Inhibitor-BIO Regulates Proliferation of Immortalized Pancreatic Mesenchymal Stem Cells (iPMSCs)

<div><h3>Background</h3><p>The small molecule 6-bromoindirubin-30-oxime (BIO), a glycogen synthase kinase 3 (GSK3) inhibitor, is a pharmacological agent known to maintain self-renewal in human and mouse embryonic stem cells (ESCs). However, the precise role of GSK3 in immortalized pancreatic mesenchymal stem cells (iPMSCs) growth and survival is not completely understood at present.</p> <h3>Results</h3><p>To determine whether this molecule is involved in controlling the proliferation of iPMSCs, we examined the effect of BIO on iPMSCs. We found that the inactivation of GSK3 by BIO can robustly stimulate iPMSCs proliferation and mass formation as shown by QRT-PCR, western blotting, 5-Bromo-2-deoxyuridine (BrdU) immunostaining assay and tunel assay. However, we did not find the related roles of BIO on β cell differentiation by immunostaining, QRT-PCR assay, glucose-stimulated insulin release and C-peptide content analysis.</p> <h3>Conclusions</h3><p>These results suggest that BIO plays a key role in the regulation of cell mass proliferation and maintenance of the undifferentiated state of iPMSCs.</p> </div

Characterization of Metabolites of Leonurine (SCM-198) in Rats after Oral Administration by Liquid Chromatography/Tandem Mass Spectrometry and NMR Spectrometry

Leonurine, a major bioactive component from Herba Leonuri, shows therapeutic potential for cardiovascular disease and stroke prevention in some preclinical experiments. The aim of this study is to characterize metabolites of leonurine in rats using high performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS). The chromatographic separation was performed on an Agilent ZORBAX SB-C18 column using a gradient elution with acetonitrile/ammonium acetate buffer (10 mM, pH 4.0) solvent system. An information dependent acquisition (IDA) method was developed for screening and identifying metabolites of leonurine under positive ion mode. Compared with control, the interesting compound in the extracted ion chromatogram (XIC) of the in vivo samples was chosen and further identified by analyzing their retention times, changes in observed mass (Δm/z), and spectral patterns of product ion utilizing advanced software tool. For the first time, a total of three metabolites were identified, including two phase II metabolites generated by glucuronidation (M1) and sulfation (M2) and one phase I metabolite formed by O-demethylation (M3). Finally, the lead metabolite M1 was isolated from urine and its structure was characterized as leonurine-10-O-β-D-glucuronide by NMR spectroscopy (1H, 13C, HMBC, and HSQC)

Pathway and Network Approaches for Identification of Cancer Signature Markers from Omics Data

The advancement of high throughput omic technologies during the past few years has made it possible to perform many complex assays in a much shorter time than the traditional approaches. The rapid accumulation and wide availability of omic data generated by these technologies offer great opportunities to unravel disease mechanisms, but also presents significant challenges to extract knowledge from such massive data and to evaluate the findings. To address these challenges, a number of pathway and network based approaches have been introduced. This review article evaluates these methods and discusses their application in cancer biomarker discovery using hepatocellular carcinoma (HCC) as an example

Improvement of resistance to rice blast and bacterial leaf streak by CRISPR/Cas9-mediated mutagenesis of Pi21 and OsSULTR3;6 in rice (Oryza sativa L.)

Rice (Oryza sativa L.) is a staple food in many countries around the world, particularly in China. The production of rice is seriously affected by the bacterial leaf streak and rice blast, which can reduce rice yield or even cause it to fail to be harvested. In this study, susceptible material 58B was edited by CRISPR/Cas9, targeting a target of the Pi21 gene and a target of the effector-binding element (EBE) of the OsSULTR3;6 gene, and the mutants 58b were obtained by Agrobacterium-mediated method. The editing efficiency of the two targets in the T0 generation was higher than 90.09%, the homozygous mutants were successfully selected in the T0 generation, and the homozygous mutation rate of each target was higher than 26.67%. The expression of the edited pi21 and EBE of Ossultr3;6 was significantly reduced, and the expression of defense responsive genes was significantly upregulated after infected with rice blast. The lesion areas of rice blast and bacterial leaf streak were significantly reduced in 58b, and the resistance of both was effectively improved. Furthermore, the gene editing events did not affect the agronomic traits of rice. In this study, the resistance of 58b to rice blast and bacterial leaf streak was improved simultaneously. This study provides a reference for using Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (CRISPR/Cas9) to accelerate the improvement of rice varieties and the development of new materials for rice breeding

Genomic selection analysis of morphological and adaptation traits in Chinese indigenous dog breeds

The significant morphological differences and abundant germplasm resources of Chinese indigenous dog breeds can be attributed to the diverse geographical environment, including plateaus, mountains, and a long history of raising dogs. The combination of both natural and artificial selection during the past several thousand years has led to hundreds of dog breeds with distinct morphological traits and environmental adaptations. China is one of the earliest countries to domesticate dogs and there are more than 50 ancient indigenous dog breeds. In this study, the run of homozygosity (ROH) and proportion of the autosomal genome covered by ROHs (FROH) were calculated for 10 dog breeds that are the most representative Chinese indigenous dogs based on 170K SNP microarray. The results of FROH showed that the Chuandong hound dogs (HCSSC) have the highest level of inbreeding among the tested breeds. The inbreeding in HCSSC occurred more recently than the Liangshan dogs (SCLSQ) dogs because of more numbers of long ROHs in HCSSC dogs, and the former also have higher inbreeding degree. In addition, there are significant differences in the inbreeding degree among different subpopulations of the same breed, such as the Thin dogs from Shaanxi and Shandong province. To explore genome-wide selection signatures among different breeds, including coat color, ear shape, and altitude adaptability, we performed genome selection analyses of FST and cross population extended haplotype homozygosity (XP-EHH). For the coat color, the FST analysis between Xiasi dogs (XSGZ) and HCSSC dogs was performed and identified multiple genes involved in coat color, hair follicle, and bone development, including MC1R, KITLG, SOX5, RSPO2, and TBX15. For the plateau adaptability, we performed FST and XP-EHH analyses between dogs from Tibet (Tibetan Mastiffs and Nyingchi dogs) and plain regions (Guangxi Biwei dogs GXBWQ and Guandong Sharpei dogs). The results showed the EPAS1 gene in dogs from Tibet undergo strong selection. Multiple genes identified for selection signals based on different usage of dogs. Furthermore, the results of ear shape analyses showed that MSRB3 was likely to be the main gene causing the drop ear of domestic dogs. Our study provides new insights into further understanding of Chinese indigenous dogs

Cost-Effectiveness Analysis Based on Intelligent Electronic Medical Arthroscopy for the Treatment of Varus Knee Osteoarthritis

The incidence of inverted knee osteoarthritis is slowly increasing, there are technical limitations in the treatment, and the operation is difficult. In this article, we will study the benefits and costs of arthroscopic cleaning treatments based on intelligent electronic medicine. This article focuses on knee osteoarthritis patients in the EL database. There are 12 male patients, accounting for 66.67%, and 6 female patients, accounting for 33.33%. The average body mass index (BMI) of the patients was 28.08, the average time from first knee discomfort to surgery was 28.44 months, and the average time of arthroscopic debridement treatment for patients with VKOH knee osteoarthritis was 143.11 minutes. One case of perioperative complication occurred within 35 days after operation, which was a soleus muscle intermuscular venous thrombosis. After immobilization and enhanced anticoagulation for 1 week, it was stable without risk of shedding. The average postoperative study time was 20.00 months. The electronic medical arthroscopy cleaning treatment plan in this article can greatly improve the quality of life of patients and can check the pathological state in time, with low cost. In the course of treatment, comprehensive treatment costs can be saved by 45%. Arthroscopic clean-up treatment can not only reduce knee pain and other uncomfortable symptoms, restore normal knee joint function, and improve the quality of life of patients, but also correct the unequal length of the lower limbs, thereby avoiding spinal degeneration caused by knee instability. Therefore, it is the first choice for the treatment of advanced knee osteoarthritis in patients with VKOH

Shape memory effect of thermoplastic segmented polyurethanes with self-complementary quadruple hydrogen bonding in soft segments

This paper describes the fact that a kind of thermoplastic shape memory polyurethane with self-complementary quadruple hydrogen bonding units in soft segments can present a significant shape memory effect under the usually used thermodynamic programming condition. Compared with the control sample, it was observed that the introduction of self-complementary quadruple hydrogen bonding into soft segments increases the glass transition temperature from 28.3 ° C to 73.3 ° C. Therefore, the temporary deformation can be fixed well after cooling at room temperature; subsequently thermal responsive shape memory recovery can be triggered by heating up to 86 ° C. The immediate shape recovery ratio and shape fixity ratio can be 95.8% and 95.9%. Even after 24 hours relaxation for the stretched films, the corresponding Rr and Rf can be 94% and 60%. In contrast, the sample without quadruple hydrogen bonding shows that the elasticity and the deformation cannot be fixed after 24 hours relaxation

Intelligent Prediction of Fan Rotation Stall in Power Plants Based on Pressure Sensor Data Measured In-Situ

Blower and exhaust fans consume over 30% of electricity in a thermal power plant, and faults of these fans due to rotation stalls are one of the most frequent reasons for power plant outage failures. To accurately predict the occurrence of fan rotation stalls, we propose a support vector regression machine (SVRM) model that predicts the fan internal pressures during operation, leaving ample time for rotation stall detection. We train the SVRM model using experimental data samples, and perform pressure data prediction using the trained SVRM model. To prove the feasibility of using the SVRM model for rotation stall prediction, we further process the predicted pressure data via wavelet-transform-based stall detection. By comparison of the detection results from the predicted and measured pressure data, we demonstrate that the SVRM model can accurately predict the fan pressure and guarantee reliable stall detection with a time advance of up to 0.0625 s. This superior pressure data prediction capability leaves significant time for effective control and prevention of fan rotation stall faults. This model has great potential for use in intelligent fan systems with stall prevention capability, which will ensure safe operation and improve the energy efficiency of power plants