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Translational bioinformatics

Xin Zhao, Yanwu Jin, Haibo Li, Yuxiu Jia, Yuelan Wang
The molecular mechanisms underlying sevoflurane (SEVO)-induced impairment of learning and memory remain unclear. Specifically, a role of microRNAs (miRNAs) in the control of the neuron proliferation in the developing brain exposed to SEVO has not been reported previously. Here, we studied the effects of SEVO exposure on the neural cell proliferation, and on the learning and memory of neonatal rats. We found that SEVO exposure significantly decreased neuron cell proliferation, reduced BDNF levels in brain, and impaired learning and memory of neonatal rats in Morris water maze test and Plus-Maze discriminative avoidance task (PM-DAT), likely through downregulation of CCNA2 protein...
December 12, 2018: Aging
Shinichiro Tsuchiya, Issaku Yamada, Kiyoko F Aoki-Kinoshita
Motivation: Glycans are biomolecules that take an important role in the biological processes of living organisms. They form diverse, complicated structures such as branched and cyclic forms. Web3 Unique Representation of Carbohydrate Structures (WURCS) was proposed as a new linear notation for uniquely representing glycans during the GlyTouCan project. WURCS defines rules for complex glycan structures that other text formats did not support, and so it is possible to represent a wide variety glycans...
December 7, 2018: Bioinformatics
Edoardo D'Angelo, Marco Agostini
Currently available high-throughput technologies combined with bioinformatics analyses revealed that nearly 80% of the genome is transcribed, whereas only 2% of the genetic code is translated in proteins. In the landscape of non-coding RNA, the long non-coding RNA (>200 nucleotides) is a newer class of ncRNAs, with a potential pivotal role in homeostatic and pathological mechanisms, confirmed by increasing emerging evidences in different diseases, especially in cancer. In parallel, recent studies have demonstrated that as cancer progresses, extracellular matrix co-evolves into an activated state through continuous biochemical and structural modifications...
December 2018: Non-Coding RNA Research
Jędrzej M Małecki, Hanneke L D M Willemen, Rita Pinto, Angela Y Y Ho, Anders Moen, Ingrid F Kjønstad, Boudewijn M T Burgering, Fried Zwartkruis, Niels Eijkelkamp, Pål Ø Falnes
Lysine methylation is an important post-translational modification that is also present on mitochondrial proteins, but the mitochondrial lysine-specific methyltransferases (KMTs) responsible for modification are in most cases unknown. Here, we set out to determine the function of human family with sequence similarity 173 member B (FAM173B), a mitochondrial methyltransferase (MTase) reported to promote chronic pain. Using bioinformatics analyses and biochemical assays, we found that FAM173B contains an atypical, non-cleavable mitochondrial targeting sequence responsible for its localization to mitochondria...
December 10, 2018: Journal of Biological Chemistry
Karen Vester, Murat Eravci, Tatsuo Serikawa, Tatjana Schütze, Christoph Weise, Jens Kurreck
Guanine-quadruplex (G-quadruplex) structures in mRNAs have been shown to modulate gene expression. However, the overall biological relevance of this process is under debate, as cellular helicases unwind G-quadruplex structures. The helicase Rhau (encoded by the DHX36 gene) was reported to be the major source of RNA G-quadruplex resolving activity in lysates of human cells. In the current study, we depleted Rhau by RNAi-mediated silencing and analyzed the effect on proteins whose mRNAs harbor a G-quadruplex motif in their 5'-UTRs...
December 5, 2018: Biochemical and Biophysical Research Communications
Fanlu Meng, Linlin Zhang
BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Previous studies revealed that miR-183-5p is frequently involved in various human cancers. However, the exact role of miR-183-5p in regulating the pathogenesis of lung cancer remains unclear. METHOD: Bioinformatic analysis, luciferase reporter assay, and Western blotting was used to investigate whether miR-183-5p directly bound to the 3'UTR of PIK3CA and prevented its translation. Furthermore, an si-miR-183-5p and PIK3CA siRNA was used to evaluate whether PIK3CA expression increased and whether cell proliferation, migration and invasion ability were promoted...
December 4, 2018: Experimental Cell Research
Xiaodong Song, Pan Xu, Chao Meng, Chenguang Song, Timothy S Blackwell, Rongrong Li, Hongbo Li, Jinjin Zhang, Changjun Lv
The role of long non-coding RNA (lncRNA) in idiopathic pulmonary fibrosis (IPF) is poorly understood. We found a novel lncRNA-ITPF that was upregulated in IPF. Bioinformatics and in vitro translation verified that lncITPF is an actual lncRNA, and its conservation is in evolution. Northern blot and rapid amplification of complementary DNA ends were used to analyze the full-length sequence of lncITPF. RNA fluorescence in situ hybridization and nucleocytoplasmic separation demonstrated that lncITPF was mainly located in the nucleus...
September 6, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Alessio Caruso, Leah B Bushin, Kenzie A Clark, Ryan J Martinie, Mohammad R Seyedsayamdost
Ribosomally-synthesized and post-translationally-modified peptides (RiPPs) are an emerging class of natural products that harbor diverse chemical functionalities, usually introduced via the action of a small number of tailoring enzymes. We have been interested in RiPP biosynthetic gene clusters that encode unusual metalloenzymes, as these may install yet unknown alterations. Using a new bioinformatic search strategy, we recently identified an array of unexplored RiPP gene clusters that are quorum sensing-regulated and contain one or more uncharacterized radical S-adenosylmethionine (RaS) metalloenzymes...
December 6, 2018: Journal of the American Chemical Society
Shicheng Yu, Chaoran Zheng, Fan Zhou, David L Baillie, Ann M Rose, Zixin Deng, Jeffrey Shih-Chieh Chu
BACKGROUND: Essential genes are required for an organism's viability and their functions can vary greatly, spreading across many pathways. Due to the importance of essential genes, large scale efforts have been undertaken to identify the complete set of essential genes and to understand their function. Studies of genome architecture and organization have found that genes are not randomly disturbed in the genome. RESULTS: Using combined genetic mapping, Illumina sequencing, and bioinformatics analyses, we successfully identified 44 essential genes with 130 lethal mutations in genomic regions of C...
December 4, 2018: BMC Genomics
Rachel Jodoin, Jean-Pierre Perreault
RNA G-quadruplexes (rG4) are stable non-canonical secondary structures composed of G-rich sequences. Many rG4 structures located in the 5'UTRs of mRNAs act as translation repressors due to their high stability which is thought to impede ribosomal scanning. That said, it is not known if these are mRNA-specific examples, or if they are indicative of a global expression regulation mechanism of the mRNAs involved in a common pathway based on structure folding recognition. Gene-ontology analysis of mRNAs bearing a predicted rG4 motif in their 5'UTRs revealed an enrichment for mRNAs associated with the colorectal cancer pathway...
2018: PloS One
Zhiye Wang, Meiyue Wang, Tian Wang, Yijing Zhang, Xiuren Zhang
Transcripts have intrinsic propensity to form stable secondary structure that is fundamental to regulate RNA transcription, splicing, translation, RNA localization and turnover. Numerous methods that integrate chemical reactions with next-generation sequencing (NGS) have been applied to study in vivo RNA structure, providing new insights into RNA biology. Dimethyl sulfate (DMS) probing coupled with mutational profiling through NGS (DMS-MaPseq) is a newly developed method for revealing genome-wide or target-specific RNA structure...
November 29, 2018: Methods: a Companion to Methods in Enzymology
RaviKanthReddy Marreddy, Xiaoqian Wu, Sapkota Madhab, Allan M Prior, Jesse Jones, Dianqing Sun, Kirk E Hevener, Julian G Hurdle
Clostridium difficile infection (CDI) is an antibiotic-induced microbiota shift disease of the large bowel. While there is a need for narrow-spectrum CDI antibiotics, it is unclear which cellular proteins are appropriate drug targets to specifically inhibit C. difficile. We evaluated the enoyl-acyl carrier protein reductase II (FabK) that catalyzes the final step of bacterial fatty acid biosynthesis. Bioinformatics showed C. difficile uses FabK as its sole enoyl-ACP reductase, unlike several major microbiota species...
December 1, 2018: ACS Infectious Diseases
Hirotaka Kanoh, Hiroyuki Kato, Yamato Suda, Aki Hori, Shoichiro Kurata, Takayuki Kuraishi
The Drosophila Toll pathway is involved in embryonic development, innate immunity, and cell-cell interactions. However, compared to the mammalian Toll-like receptor innate immune pathway, its intracellular signaling mechanisms are not fully understood. We have previously performed a series of ex vivo genome-wide RNAi screenings to identify genes required for the activation of the Toll pathway. In this study, we have conducted an additional genome-wide RNAi screening using the overexpression of Tube, an adapter molecule in the Toll pathway, and have performed a co-immunoprecipitation assay to identify components present in the dMyd88-Tube complex...
November 26, 2018: Biochemical and Biophysical Research Communications
Antonino Fiannaca, Massimo La Rosa, Laura La Paglia, Alfonso Urso
BACKGROUND: microRNAs act as regulators of gene expression interacting with their gene targets. Current bioinformatics services, such as databases of validated miRNA-target interactions and prediction tools, usually provide interactions without any information about what tissue that interaction is more likely to appear nor information about the type of interactions, causing mRNA degradation or translation inhibition respectively. RESULTS: In this work, we introduce miRTissue, a web application that combines validated miRNA-target interactions with statistical correlation among expression profiles of miRNAs, genes and proteins in 15 different human tissues...
November 30, 2018: BMC Bioinformatics
D K Hapangama, J Drury, L Da Silva, H Al-Lamee, A Earp, A J Valentijn, D P Edirisinghe, P A Murray, A T Fazleabas, C E Gargett
STUDY QUESTION: Is endometriosis associated with abnormally located endometrial basalis-like (SSEA1+/SOX9+) cells in the secretory phase functionalis and could they contribute to ectopic endometriotic lesion formation? SUMMARY ANSWER: Women with endometriosis had an abnormally higher number of basalis-like SSEA1+/SOX9+ epithelial cells present in the stratum functionalis and, since these cells formed 3D structures in vitro with phenotypic similarities to ectopic endometriotic lesions, they may generate ectopic lesions following retrograde menstruation...
November 29, 2018: Human Reproduction
Zhi-Peng You, Yu-Lan Zhang, Bing-Yang Li, Xin-Gen Zhu, Ke Shi
Purpose: Intricate signaling networks and transcriptional regulators translate pathogen recognition into defense responses. The aim of this study was to identify the weighted genes involved in diabetic retinopathy (DR) in different rodent models of diabetes. Methods: We performed a gene coexpression analysis of publicly available microarray data, namely, the GSE19122 dataset from the Gene Expression Omnibus database. We conducted gene coexpression analysis on the microarray data to identify modules of functionally related coexpressed genes that are differentially expressed in different rodent models...
November 1, 2018: Investigative Ophthalmology & Visual Science
Vaishnavi Ravikumar, Nicolas C Nalpas, Viktoria Anselm, Karsten Krug, Maša Lenuzzi, Martin Sebastijan Šestak, Tomislav Domazet-Lošo, Ivan Mijakovic, Boris Macek
Bacillus subtilis is a sporulating Gram-positive bacterium widely used in basic research and biotechnology. Despite being one of the best-characterized bacterial model organism, recent proteomics studies identified only about 50% of its theoretical protein count. Here we combined several hundred MS measurements to obtain a comprehensive map of the proteome, phosphoproteome and acetylome of B. subtilis grown at 37 °C in minimal medium. We covered 75% of the theoretical proteome (3,159 proteins), detected 1,085 phosphorylation and 4,893 lysine acetylation sites and performed a systematic bioinformatic characterization of the obtained data...
November 22, 2018: Scientific Reports
Petr Tomek, Shanti K Gore, Chloe L Potts, Cristin G Print, Michael A Black, Ariane Hallermayr, Michael Kilian, Evelyn Sattlegger, Lai-Ming Ching
BACKGROUND: Depletion of tryptophan and the accumulation of tryptophan metabolites mediated by the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1), trigger immune cells to undergo apoptosis. However, cancer cells in the same microenvironment appear not to be affected. Mechanisms whereby cancer cells resist accelerated tryptophan degradation are not completely understood. We hypothesize that cancer cells co-opt IMPACT (the product of IMPrinted and AnCienT gene), to withstand periods of tryptophan deficiency...
November 22, 2018: Cell Communication and Signaling: CCS
Yuan Sheng Zhang, Lin Xia, Jian Sang, Man Li, Lin Liu, Meng Wei Li, Guang Yi Niu, Jia Bao Cao, Xu Fei Teng, Qing Zhou, Zhang Zhang
Omics data in life and health sciences are of fundamental significance for scientific research and biomedical technology development. However, there is yet to be a platform for biological data management and sharing in China, making it difficult to meet the development needs of biomedical and related fields and consequently leading to severe issues in big data management, sharing and translation. To address these issues, Beijing Institute of Genomics (BIG) of Chinese Academy of Sciences founded the BIG Data Center (BIGD) in 2016, which is dedicated to establish a biological big data management platform and multi-omics databases, with a particular focus on national population healthcare and important strategic biological resources...
November 20, 2018: Yi Chuan, Hereditas
Gang Peng, Rashaun Wilson, Yishuo Tang, TuKiet T Lam, Angus C Nairn, Kenneth Williams, Hongyu Zhao
Summary: Large-scale, quantitative proteomics data are being generated at ever increasing rates by high-throughput, mass spectrometry technologies. However, due to the complexity of these large datasets as well as the increasing numbers of post-translational modifications (PTMs) that are being identified, developing effective methods for proteomic visualization has been challenging. ProteomicsBrowser was designed to meet this need for comprehensive data visualization. Using peptide information files exported from mass spectrometry search engines or quantitative tools as input, the peptide sequences are aligned to an internal protein database such as UniProtKB...
November 21, 2018: Bioinformatics
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