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https://www.readbyqxmd.com/read/28640862/a-biosystems-approach-to-identify-the-molecular-signaling-mechanisms-of-tmem30a-during-tumor-migration
#1
Jiao Wang, Qian Wang, Dongfang Lu, Fangfang Zhou, Dong Wang, Ruili Feng, Kai Wang, Robert Molday, Jiang Xie, Tieqiao Wen
Understanding the molecular mechanisms underlying cell migration, which plays an important role in tumor growth and progression, is critical for the development of novel tumor therapeutics. Overexpression of transmembrane protein 30A (TMEM30A) has been shown to initiate tumor cell migration, however, the molecular mechanisms through which this takes place have not yet been reported. Thus, we propose the integration of computational and experimental approaches by first predicting potential signaling networks regulated by TMEM30A using a) computational biology methods, b) our previous mass spectrometry results of the TMEM30A complex in mouse tissue, and c) a number of migration-related genes manually collected from the literature, and subsequently performing molecular biology experiments including the in vitro scratch assay and real-time quantitative polymerase chain reaction (qPCR) to validate the reliability of the predicted network...
2017: PloS One
https://www.readbyqxmd.com/read/28640810/lassim-a-network-inference-toolbox-for-genome-wide-mechanistic-modeling
#2
Rasmus Magnusson, Guido Pio Mariotti, Mattias Köpsén, William Lövfors, Danuta R Gawel, Rebecka Jörnsten, Jörg Linde, Torbjörn Nordling, Elin Nyman, Sylvie Schulze, Colm E Nestor, Huan Zhang, Gunnar Cedersund, Mikael Benson, Andreas Tjärnberg, Mika Gustafsson
Recent technological advancements have made time-resolved, quantitative, multi-omics data available for many model systems, which could be integrated for systems pharmacokinetic use. Here, we present large-scale simulation modeling (LASSIM), which is a novel mathematical tool for performing large-scale inference using mechanistically defined ordinary differential equations (ODE) for gene regulatory networks (GRNs). LASSIM integrates structural knowledge about regulatory interactions and non-linear equations with multiple steady state and dynamic response expression datasets...
June 22, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28636946/ptbp2-controls-an-alternative-splicing-network-required-for-cell-communication-during-spermatogenesis
#3
Molly M Hannigan, Leah L Zagore, Donny D Licatalosi
Alternative splicing has essential roles in development. Remarkably, spermatogenic cells express more alternatively spliced RNAs compared to most whole tissues; however, regulation of these RNAs remains unclear. Here, we characterize the alternative splicing landscape during spermatogenesis and reveal an essential function for the RNA-binding protein Ptbp2 in this highly regulated developmental program. We found that Ptbp2 controls a network of genes involved in cell adhesion, migration, and polarity, suggesting that splicing regulation by Ptbp2 is critical for germ cell communication with Sertoli cells (multifunctional somatic cells necessary for spermatogenesis)...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28635594/translation-repression-via-modulation-of-the-cytoplasmic-poly-a-binding-protein-in-the-inflammatory-response
#4
Xu Zhang, Xiaoli Chen, Qiuying Liu, Shaojie Zhang, Wenqian Hu
Gene expression is precisely regulated during the inflammatory response to control infection and limit the detrimental effects of inflammation. Here, we profiled global mRNA translation dynamics in the mouse primary macrophage-mediated inflammatory response and identified hundreds of differentially translated mRNAs. These mRNAs' 3'UTRs have enriched binding motifs for several RNA-binding proteins, which implies extensive translational regulatory networks. We characterized one such protein, Zfp36, as a translation repressor...
June 21, 2017: ELife
https://www.readbyqxmd.com/read/28635300/pyridine-dinucleotides-from-molecules-to-man
#5
Joshua P Fessel, William M Oldham
SIGNIFICANCE: Pyridine dinucleotides, NAD and NADP, were discovered over 100 years ago as necessary cofactors for fermentation in yeast extracts. Since that time, these molecules have been recognized as fundamental players in a variety of cellular processes, including energy metabolism, redox homeostasis, cellular signaling, and gene transcription, among many others. Given their critical role as mediators of cellular responses to metabolic perturbations, it is unsurprising that dysregulation of NAD and NADP metabolism has been associated with the pathobiology of many chronic human diseases...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28630873/an-integrative-developmental-genomics-and-systems-biology-approach-to-identify-an-in-vivo-sox-trio-mediated-gene-regulatory-network-in-murine-embryos
#6
Wenqing Jean Lee, Sumantra Chatterjee, Sook Peng Yap, Siew Lan Lim, Xing Xing, Petra Kraus, Wenjie Sun, Xiaoming Hu, V Sivakamasundari, Hsiao Yun Chan, Prasanna R Kolatkar, Shyam Prabhakar, Thomas Lufkin
Embryogenesis is an intricate process involving multiple genes and pathways. Some of the key transcription factors controlling specific cell types are the Sox trio, namely, Sox5, Sox6, and Sox9, which play crucial roles in organogenesis working in a concerted manner. Much however still needs to be learned about their combinatorial roles during this process. A developmental genomics and systems biology approach offers to complement the reductionist methodology of current developmental biology and provide a more comprehensive and integrated view of the interrelationships of complex regulatory networks that occur during organogenesis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28629776/unveiling-the-non-repair-face-of-the-base-excision-repair-pathway-in-rna-processing-a-missing-link-between-dna-repair-and-gene-expression
#7
REVIEW
Giulia Antoniali, Matilde Clarissa Malfatti, Gianluca Tell
The Base Excision Repair (BER) pathway, initially studied as a mere DNA repair pathway, has been later found to be implicated in the expression of cancer related genes in human. For several years, this intricate involvement in apparently different processes represented a mystery, which we now are starting to unveil. The BER handles simple alkylation and oxidative lesions arising from both endogenous and exogenous sources, including cancer therapy agents. Surprisingly, BER pathway involvement in transcriptional regulation, immunoglobulin variability and switch recombination, RNA metabolism and nucleolar function is astonishingly consolidating...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28628618/solving-the-influence-maximization-problem-reveals-regulatory-organization-of-the-yeast-cell-cycle
#8
David L Gibbs, Ilya Shmulevich
The Influence Maximization Problem (IMP) aims to discover the set of nodes with the greatest influence on network dynamics. The problem has previously been applied in epidemiology and social network analysis. Here, we demonstrate the application to cell cycle regulatory network analysis for Saccharomyces cerevisiae. Fundamentally, gene regulation is linked to the flow of information. Therefore, our implementation of the IMP was framed as an information theoretic problem using network diffusion. Utilizing more than 28,000 regulatory edges from YeastMine, gene expression dynamics were encoded as edge weights using time lagged transfer entropy, a method for quantifying information transfer between variables...
June 19, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28623929/the-potential-regulatory-mechanisms-of-the-gonadotropin-releasing-hormone-in-gonadotropin-transcriptions-identified-with-bioinformatics-analyses
#9
Wei Xiang, Baoyun Zhang, Fenglin Lv, Guangde Feng, Long Chen, Fang Yang, Ke Zhang, Chunyu Cao, Pingqing Wang, Mingxing Chu
BACKGROUND: The regulation of gonadotropin synthesis and release by gonadotropin-releasing hormone (GnRH) plays an essential role in the neuroendocrine control of reproduction. However, the mechanisms underlying gonadotropin regulation by GnRH pulse frequency and amplitude are still ambiguous. This study aimed to explore the molecular mechanisms and biological pathways associated with gonadotropin synthesis by GnRH pulse frequencies and amplitudes. METHODS: Using GSE63251 datasets downloaded from the Gene Expression Omnibus (GEO), differentially expressed genes (DEGs) were screened by comparing the RNA expression from the GnRH pulse group, the GnRH tonic group and the control group...
June 17, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28623592/computational-approaches-to-study-gene-regulatory-networks
#10
Nooshin Omranian, Zoran Nikoloski
The goal of the gene regulatory network (GRN) inference is to determine the interactions between genes given heterogeneous data capturing spatiotemporal gene expression. Since transcription underlines all cellular processes, the inference of GRN is the first step in deciphering the determinants of the dynamics of biological systems. Here, we first describe the generic steps of the inference approaches that rely on similarity measures and group the similarity measures based on the computational methodology used...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28623587/generation-of-dtales-and-libraries-of-synthetic-tale-activated-promoters-for-engineering-of-gene-regulatory-networks-in-plants
#11
Tom Schreiber, Alain Tissier
Transcription factors with programmable DNA-binding specificity constitute valuable tools for the design of orthogonal gene regulatory networks for synthetic biology. Transcription activator-like effectors (TALEs), as natural transcription regulators, were used to design, build, and test libraries of synthetic TALE-activated promoters (STAPs) that show a broad range of expression levels in plants. In this chapter, we present protocols for the construction of artificial TALEs and corresponding STAPs.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28623581/analysis-of-a-plant-transcriptional-regulatory-network-using-transient-expression-systems
#12
Sara Díaz-Triviño, Yuchen Long, Ben Scheres, Ikram Blilou
In plant biology, transient expression systems have become valuable approaches used routinely to rapidly study protein expression, subcellular localization, protein-protein interactions, and transcriptional activity prior to in vivo studies. When studying transcriptional regulation, luciferase reporter assays offer a sensitive readout for assaying promoter behavior in response to different regulators or environmental contexts and to confirm and assess the functional relevance of predicted binding sites in target promoters...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28619522/integrated-analysis-of-paraquat-induced-micrornas-mrnas-changes-in-human-neural-progenitor-cells
#13
Mengling Yan, Tingting Dou, Wen Lv, Xinjin Wang, Lina Zhao, Xiuli Chang, Zhijun Zhou
Paraquat (PQ), one of the most widely used fast-acting and non-selective herbicides in the world is believed to act as a neurotoxicant, which increases the risk of developing Parkinson's disease (PD) by selectively impairing dopaminergic neurons. However, the mechanism of PQ on neural progenitor cells remains unclear. As regulator of mRNA expression, miRNA play a crucial role in neurotoxicity. Based on our previous study, we chose 10μM PQ, which induced ROS production and inhibited proliferation but not reduced the cell viability...
June 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28615495/a-bayesian-approach-to-estimating-hidden-variables-as-well-as-missing-and-wrong-molecular-interactions-in-ordinary-differential-equation-based-mathematical-models
#14
Benjamin Engelhardt, Maik Kschischo, Holger Fröhlich
Ordinary differential equations (ODEs) are a popular approach to quantitatively model molecular networks based on biological knowledge. However, such knowledge is typically restricted. Wrongly modelled biological mechanisms as well as relevant external influence factors that are not included into the model are likely to manifest in major discrepancies between model predictions and experimental data. Finding the exact reasons for such observed discrepancies can be quite challenging in practice. In order to address this issue, we suggest a Bayesian approach to estimate hidden influences in ODE-based models...
June 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28613020/integrated-gene-expression-profiling-and-chromatin-immunoprecipitation-followed-by-sequencing-analysis-of-the-c-terminal-binding-protein-in-breast-cancer
#15
Lu Chen, Yang Yang, Liwei Xu, Rui Liu, Yali Wang
AIM: This study explored the possible mechanisms of the transcriptional regulatory activities of C-terminal binding protein (CtBP) and the role of CtBP in the pathogenesis of breast cancer. METHODS: Microarray data of GSE36529, including three CtBP-knockdown breast cancer MCF-7 cell samples, three control knockdown samples and data of CtBP binding profile in MCF-7 cells, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened between CtBP-knockdown MCF-7 cell samples and controls...
June 14, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28610888/applying-differential-dynamic-logic-to-reconfigurable-biological-networks
#16
Daniel Figueiredo, Manuel A Martins, Madalena Chaves
Qualitative and quantitative modeling frameworks are widely used for analysis of biological regulatory networks, the former giving a preliminary overview of the system's global dynamics and the latter providing more detailed solutions. Another approach is to model biological regulatory networks as hybrid systems, i.e., systems which can display both continuous and discrete dynamic behaviors. Actually, the development of synthetic biology has shown that this is a suitable way to think about biological systems, which can often be constructed as networks with discrete controllers, and present hybrid behaviors...
June 10, 2017: Mathematical Biosciences
https://www.readbyqxmd.com/read/28604728/identification-of-19-new-risk-loci-and-potential-regulatory-mechanisms-influencing-susceptibility-to-testicular-germ-cell-tumor
#17
Kevin Litchfield, Max Levy, Giulia Orlando, Chey Loveday, Philip J Law, Gabriele Migliorini, Amy Holroyd, Peter Broderick, Robert Karlsson, Trine B Haugen, Wenche Kristiansen, Jérémie Nsengimana, Kerry Fenwick, Ioannis Assiotis, ZSofia Kote-Jarai, Alison M Dunning, Kenneth Muir, Julian Peto, Rosalind Eeles, Douglas F Easton, Darshna Dudakia, Nick Orr, Nora Pashayan, D Timothy Bishop, Alison Reid, Robert A Huddart, Janet Shipley, Tom Grotmol, Fredrik Wiklund, Richard S Houlston, Clare Turnbull
Genome-wide association studies (GWAS) have transformed understanding of susceptibility to testicular germ cell tumors (TGCTs), but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totaling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, roughly doubling the number of known TGCT risk loci to 44. By performing in situ Hi-C in TGCT cells, we provide evidence for a network of physical interactions among all 44 TGCT risk SNPs and candidate causal genes...
June 12, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28602952/a-novel-technique-to-combine-and-analyse-spatial-and-temporal-expression-datasets-a-case-study-with-the-sea-anemone-nematostella-vectensis-to-identify-potential-gene-interactions
#18
Amir M Abdol, Eric Röttinger, Fredrik Jansson, Jaap A Kaandorp
Understanding genetic interactions during early development of a given organism, is the first step toward unveiling gene regulatory networks (GRNs) that govern a biological process of interest. Predicting such interactions from large expression datasets by performing targeted knock-down/knock-out approaches is a challenging task. We use the currently available expression datasets (in situ hybridization images & qPCR time series) for a basal anthozoan the sea anemone N. vectensis to construct continuous spatiotemporal gene expression patterns during its early development...
June 8, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28602483/a-hybrid-framework-for-reverse-engineering-of-robust-gene-regulatory-networks
#19
Mina Jafari, Behnam Ghavami, Vahid Sattari
The inference of Gene Regulatory Networks (GRNs) using gene expression data in order to detect the basic cellular processes is a key issue in biological systems. Inferring GRN correctly requires inferring predictor set accurately. In this paper, a fast and accurate predictor set inference framework which linearly combines some inference methods is proposed. The purpose of the combination of various methods is to increase the accuracy of inferred GRN. The proposed framework offers a linear weighted combination of Pearson Correlation Coefficient (PCC) and two different feature selection approaches, namely: Information Gain (IG) and ReliefF...
June 8, 2017: Artificial Intelligence in Medicine
https://www.readbyqxmd.com/read/28600837/single-cell-analyses-to-reveal-hematopoietic-stem-cell-fate-decisions
#20
REVIEW
Ilaria Lunger, Malak Fawaz, Michael A Rieger
Hematopoietic stem cells (HSCs) are the best studied adult stem cells with enormous clinical value. Most of our knowledge about their biology relies on assays at the single HSC level. However, only the recent advances in developing new single cell technologies allowed the elucidation of the complex regulation of HSC fate decision control. This Review will focus on current attempts to investigate individual HSCs at molecular and functional levels. The advantages of these technologies leading to groundbreaking insights into hematopoiesis will be highlighted, and the challenges facing these technologies will be discussed...
June 10, 2017: FEBS Letters
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