The Regulatory Role of MeAIB in Protein Metabolism and the mTOR Signaling Pathway in Porcine Enterocytes.

Amino acid transporters play an important role in cell growth and metabolism. MeAIB, a transporter-selective substrate, often represses the adaptive regulation of sodium-coupled neutral amino acid transporter 2 (SNAT2), which may act as a receptor and regulate cellular amino acid contents, therefore modulating cellular downstream signaling. The aim of this study was to investigate the effects of MeAIB to SNAT2 on cell proliferation, protein turnover, and the mammalian target of rapamycin (mTOR) signaling pathway in porcine enterocytes. Intestinal porcine epithelial cells (IPEC)-J2 cells were cultured in a high-glucose Dulbecco's modified Eagle's (DMEM-H) medium with 0 or 5 mmoL/L System A amino acid analogue (MeAIB) for 48 h. Cells were collected for analysis of proliferation, cell cycle, protein synthesis and degradation, intracellular free amino acids, and the expression of key genes involved in the mTOR signaling pathway. The results showed that SNAT2 inhibition by MeAIB depleted intracellular concentrations of not only SNAT2 amino acid substrates but also of indispensable amino acids (methionine and leucine), and suppressed cell proliferation and impaired protein synthesis. MeAIB inhibited mTOR phosphorylation, which might be involved in three translation regulators, EIF4EBP1, IGFBP3, and DDIT4 from PCR array analysis of the 84 genes related to the mTOR signaling pathway. These results suggest that SNAT2 inhibition treated with MeAIB plays an important role in regulating protein synthesis and mTOR signaling, and provide some information to further clarify its roles in the absorption of amino acids and signal transduction in the porcine small intestine

Unlocking the mystery of the hard-to-sequence phage genome: PaP1 methylome and bacterial immunity

BACKGROUND: Whole-genome sequencing is an important method to understand the genetic information, gene function, biological characteristics and survival mechanisms of organisms. Sequencing large genomes is very simple at present. However, we encountered a hard-to-sequence genome of Pseudomonas aeruginosa phage PaP1. Shotgun sequencing method failed to complete the sequence of this genome. RESULTS: After persevering for 10 years and going over three generations of sequencing techniques, we successfully completed the sequence of the PaP1 genome with a length of 91,715 bp. Single-molecule real-time sequencing results revealed that this genome contains 51 N-6-methyladenines and 152 N-4-methylcytosines. Three significant modified sequence motifs were predicted, but not all of the sites found in the genome were methylated in these motifs. Further investigations revealed a novel immune mechanism of bacteria, in which host bacteria can recognise and repel modified bases containing inserts in a large scale. This mechanism could be accounted for the failure of the shotgun method in PaP1 genome sequencing. This problem was resolved using the nfi(-) mutant of Escherichia coli DH5α as a host bacterium to construct a shotgun library. CONCLUSIONS: This work provided insights into the hard-to-sequence phage PaP1 genome and discovered a new mechanism of bacterial immunity. The methylome of phage PaP1 is responsible for the failure of shotgun sequencing and for bacterial immunity mediated by enzyme Endo V activity; this methylome also provides a valuable resource for future studies on PaP1 genome replication and modification, as well as on gene regulation and host interaction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-803) contains supplementary material, which is available to authorized users

On the preprocessing and postprocessing of HRTF individualization based on sparse representation of anthropometric features

Individualization of head-related transfer functions (HRTFs) can be realized using the person's anthropometry with a pretrained model. This model usually establishes a direct linear or non-linear mapping from anthropometry to HRTFs in the training database. Due to the complex relation between anthropometry and HRTFs, the accuracy of this model depends heavily on the correct selection of the anthropometric features. To alleviate this problem and improve the accuracy of HRTF individualization, an indirect HRTF individualization framework was proposed recently, where HRTFs are synthesized using a sparse representation trained from the anthropometric features. In this paper, we extend their study on this framework by investigating the effects of different preprocessing and postprocessing methods on HRTF individualization. Our experimental results showed that preprocessing and postprocessing methods are crucial for achieving accurate HRTF individualization

A study assessing the association of glycated hemoglobin a1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of asian ancestry

10.1371/journal.pone.0079767PLoS ONE811-POLN

No evidence for a common blood microbiome based on a population study of 9,770 healthy humans

Human blood is conventionally considered sterile but recent studies suggest the presence of a blood microbiome in healthy individuals. Here we characterized the DNA signatures of microbes in the blood of 9,770 healthy individuals using sequencing data from multiple cohorts. After filtering for contaminants, we identified 117 microbial species in blood, some of which had DNA signatures of microbial replication. They were primarily commensals associated with the gut (n = 40), mouth (n = 32) and genitourinary tract (n = 18), and were distinct from pathogens detected in hospital blood cultures. No species were detected in 84% of individuals, while the remainder only had a median of one species. Less than 5% of individuals shared the same species, no co-occurrence patterns between different species were observed and no associations between host phenotypes and microbes were found. Overall, these results do not support the hypothesis of a consistent core microbiome endogenous to human blood. Rather, our findings support the transient and sporadic translocation of commensal microbes from other body sites into the bloodstream

Evolutionary game based access class barring for machine-to-machine communications

Machine-to-machine (M2M) communication faces the most critical challenge that when a massive number of MTC devices perform random access, there will be severe congestions. 3GPP developed a network coordinated random access stabilization scheme known as the access class barring(ACB) to deal with the problem in LTE-Advanced. However, MTC devices in overlapped areas still suffer severe access delays due to the noncooperation and individual setting of ACB factor among BSs. We propose evolutionary game based ACB algorithm to help MTC devices alleviate congestions and thus eliminate substantial defects in the ordinary ACB. Finally, the performance of the evolutionary game based ACB algorithm is analysed, and simulation results show the convergence and effectiveness of the proposed algorithm. ? 2014 Global IT Research Institute (GIRI).EICPCI-S(ISTP)

Joint transceiving scheme for multi-beam GEO satellite communications system

In multi-beam satellite communication systems, users suffer from 3dB power attenuation in beam-edge area. This problem also exists in terrestrial cellular network. To solve this problem, terrestrial system employs joint transceiving that makes adjacent cells transmit signals together. The purpose of this paper is to propose a method of joint transceiving by compositing beams for satellite systems. The equal-gain combination algorithm is presented to simplify beams from component beams. Then we propose a joint transceiving scheme based on component beams based on a simplified processing algorithm. Simulation results show that SIR of users in beam-edge increases by 6dB when using the joint transceiving scheme. ? 2014 Global IT Research Institute (GIRI).EICPCI-S(ISTP)

Green synthesis of biogenetic Te(0) nanoparticles by high tellurite tolerance fungus Mortierella sp. AB1 with antibacterial activity

Tellurite [Te(IV)] is a high-toxicity metalloid. In this study, a fungus with high Te(IV) resistance was isolated. Strain AB1 could efficiently reduce highly toxic Te(IV) to less toxic Te(0). The reduced products formed rod-shaped biogenetic Te(0) nanoparticles (Bio-TeNPs) intracellularly. Further TEM-element mapping, FTIR, and XPS analysis showed that the extracted Bio-TeNPs ranged from 100 to 500 nm and consisted of Te(0), proteins, lipids, aromatic compounds, and carbohydrates. Moreover, Bio-TeNPs exhibited excellent antibacterial ability against Shigella dysenteriae, Escherichia coli, Enterobacter sakazakii, and Salmonella typhimurium according to inhibition zone tests. Further growth and live/dead staining experiments showed that E. coli and S. typhimurium were significantly inhibited by Bio-TeNPs, and cells were broken or shriveled after treatment with Bio-TeNPs based on SEM observation. Additionally, the antioxidant and cytotoxicity tests showed that the Bio-TeNPs exhibited excellent antioxidant capacity with no cytotoxicity. All these results suggested that strain AB1 showed great potential in bioremediation and Bio-TeNPs were excellent antibacterial nanomaterials with no cytotoxicity.Peer reviewe

The Combination of Tumor Mutational Burden and T-Cell Receptor Repertoire Predicts the Response to Immunotherapy in Patients With Advanced Non-Small Cell Lung Cancer

Tumor mutational burden (TMB) and T-cell receptor (TCR) might predict the response to immunotherapy in patients with non-small cell lung cancer (NSCLC). However, the predictive value of the combination of TMB and TCR was not clear. Targeted DNA and TCR sequencing were performed on tumor biopsy specimens. We combined TMB and TCR diversity into a TMB-and-TCR (TMR) score using logistic regression. In total, 38 patients with advanced NSCLC were divided into a discovery set

Extracellular vesicles in gastric cancer: role of exosomal lncRNA and microRNA as diagnostic and therapeutic targets

Extracellular vesicles (EVs), including exosomes, play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of gastric cancer. This review discusses the current understanding of the role of EVs, particularly exosomal lncRNA and microRNA, in gastric cancer and their potential as diagnostic and therapeutic targets. Exosomes are small membrane-bound particles secreted by both cancer cells and stromal cells within the tumor microenvironment. They contain various ncRNA and biomolecules, which can be transferred to recipient cells to promote tumor growth and metastasis. In this review, we highlighted the importance of exosomal lncRNA and microRNA in gastric cancer. Exosomal lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. We also discuss the potential use of exosomal lncRNAs and microRNAs as diagnostic biomarkers for gastric cancer. Exosomes can be isolated from various bodily fluids, including blood, urine, and saliva. They contain specific molecules that reflect the molecular characteristics of the tumor, making them promising candidates for non-invasive diagnostic tests. Finally, the potential of targeting exosomal lncRNAs and microRNAs as a therapeutic strategy for gastric cancer were reviewed as wee. Inhibition of specific molecules within exosomes has been shown to suppress tumor growth and metastasis in preclinical models. In conclusion, this review article provides an overview of the current understanding of the role of exosomal lncRNA and microRNA in gastric cancer. We suggest that further research into these molecules could lead to new diagnostic tools and therapeutic strategies for this deadly disease