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biological regulatory network

Jean-Baptiste Lugagne, Sebastián Sosa Carrillo, Melanie Kirch, Agnes Köhler, Gregory Batt, Pascal Hersen
Cybergenetics is a novel field of research aiming at remotely pilot cellular processes in real-time with to leverage the biotechnological potential of synthetic biology. Yet, the control of only a small number of genetic circuits has been tested so far. Here we investigate the control of multistable gene regulatory networks, which are ubiquitously found in nature and play critical roles in cell differentiation and decision-making. Using an in silico feedback control loop, we demonstrate that a bistable genetic toggle switch can be dynamically maintained near its unstable equilibrium position for extended periods of time...
November 17, 2017: Nature Communications
Nathan Salomonis
The analysis of proteomics data can be significantly challenging. Beyond the technical challenges of accurately identifying and quantifying peptides, identifying the most biologically coherent set of biomarkers can be a particularly daunting step. In this chapter, we will review a series of methods implemented in the software AltAnalyze that can be used to normalize proteomics peptide counts, identify a minimal set of the most distinguishing morbidity-associated biomarkers, and connect up these results to known pathways and interacting protein and regulatory networks...
November 18, 2017: Methods in Molecular Biology
Vladimir V Sherstyuk, Sergey P Medvedev, Suren M Zakian
Pluripotent stem cells have great potential for developmental biology and regenerative medicine. Embryonic stem cells, which are obtained from blastocysts, and induced pluripotent stem cells, which are generated by the reprogramming of somatic cells, are two main types of pluripotent cells. It is important to understand the regulatory network that controls the pluripotency state and reprogramming process. Various types of noncoding RNAs (ncRNAs) have emerged as substantial components of regulatory networks...
November 15, 2017: Stem Cell Reviews
Zhihui Zhong, Sifeng Mao, Haifeng Lin, Jin-Ming Lin, Jianhua Lin
Osteosarcoma is the most common malignant tumour found in bones, and it has a poor prognosis. For improved therapy, it is significant to have a deep understanding of the proteomics changes in the cancer stem cells (CSCs) of osteosarcoma. Therefore, a comparative proteomics approach based on ultra-high-performance liquid chromatography coupled to an Orbitrap Fusion mass spectrometer (UHPLC-Orbitrap Fusion MS) was established to investigate the key molecular changes between CSCs and non-CSCs in human osteosarcoma HOS cells...
February 1, 2018: Talanta
Entai Hou, Xian Li, Zerong Liu, Fuchang Zhang, Zhongmin Tian
Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased level of fumarate and decreased level of malate and exacerbated salt-induced hypertension. To gain insights into the metabolism profiles that induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC-MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient HUVEC cells and negative controls...
November 11, 2017: Biomedical Chromatography: BMC
Caroline Medioni, Florence Besse
The last past decade has witnessed a revolution in our appreciation of transcriptome complexity and regulation. This remarkable expansion in our knowledge largely originates from the advent of high-throughput methodologies, and the consecutive discovery that up to 90% of eukaryotic genomes are transcribed, thus generating an unanticipated large range of noncoding RNAs (Hangauer et al., 15(4):112, 2014). Besides leading to the identification of new noncoding RNA species, transcriptome-wide studies have uncovered novel layers of posttranscriptional regulatory mechanisms controlling RNA processing, maturation or translation, and each contributing to the precise and dynamic regulation of gene expression...
2018: Methods in Molecular Biology
Lian Zhou, Shuang Sun, Wei Zhang, Ya-Wen He
Molecules of the diffusible signal factor (DSF) family represent a class of widely conserved quorum-sensing signals used by many Gram-negative bacterial pathogens. The measurement of DSF family signals is essential for understanding their biological roles, signaling pathway, and regulatory network. We are presenting here methods for extraction and purification of DSF family signals from culture supernatants, and further quantification of members of DSF family signals using an ultra-performance liquid chromatographic system (UPLC) coupled with an accurate time-of-flight mass spectrometry (TOF-MS) analysis...
2018: Methods in Molecular Biology
Xiaomei Sun, Zhigang Li, Hang Liu, Jun Yang, Wenxing Liang, You-Liang Peng, Jinguang Huang
Lysine acetylation is a major post-translational modification that plays important regulatory roles in diverse biological processes to perform various cellular functions in both eukaryotes and prokaryotes. However, roles of lysine acetylation in plant fungal pathogens were less studied. Here, we provided the first lysine acetylome of vegetative hyphae of the rice blast fungus Magnaporthe oryzae through a combination of highly sensitive immune-affinity purification and high-resolution LC-MS/MS. This lysine acetylome had 2,720 acetylation sites in 1,269 proteins...
November 10, 2017: Scientific Reports
Noopur Singh, Ashok Sharma
Turmeric has been used as a therapeutic herb over centuries in traditional medicinal systems due to the presence of several secondary metabolite compounds. microRNAs are known to regulate gene expression at the post-transcriptional level by transcriptional cleavage or translation repression. miRNAs have been demonstrated to play an active role in secondary metabolism regulation. The present work was focused on the identification of the miRNAs involved in the regulation of secondary metabolite and development process of turmeric...
November 7, 2017: Comptes Rendus Biologies
Heng Li, Dan Wang, Yongjian Yuan, Jikang Min
Osteoarthritis (OA) is the most common joint disorder and affects approximately half of the aged population. Current treatments for OA are largely palliative until the articular cartilage has been deeply damaged and irreversible morphological changes appear. Thus, effective methods are needed for diagnosing and monitoring the progression of OA during its early stages when therapeutic drugs or biological agents are most likely to be effective. Various proteinases involved in articular cartilage degeneration in pre-OA conditions, which may represent the earliest reversible measurable changes, are considered diagnostic and therapeutic targets for early OA...
November 10, 2017: Arthritis Research & Therapy
Ming Shi, Weiming Shen, Yanwen Chong, Hong-Qiang Wang
Inferring gene regulatory networks (GRNs) from gene expression data is an important but challenging issue in systems biology. Here, the authors propose a dictionary learning-based approach that aims to infer GRNs by globally mining regulatory signals, known or latent. Gene expression is often regulated by various regulatory factors, some of which are observed and some of which are latent. The authors assume that all regulators are unknown for a target gene and the expression of the target gene can be mapped into a regulatory space spanned by all the regulators...
December 2017: IET Systems Biology
Xiaohan Zhang, Shenquan Liu, Feibiao Zhan, Jing Wang, Xiaofang Jiang
The damage of dopaminergic neurons that innervate the striatum has been considered to be the proximate cause of Parkinson's disease (PD). In the dopamine-denervated state, the loss of dendritic spines and the decrease of dendritic length may prevent medium spiny neuron (MSN) from receiving too much excitatory stimuli from the cortex, thereby reducing the symptom of Parkinson's disease. However, the reduction in dendritic spine density obtained by different experiments is significantly different. We developed a biological-based network computational model to quantify the effect of dendritic spine loss and dendrites tree degeneration on basal ganglia (BG) signal regulation...
2017: Frontiers in Computational Neuroscience
Fereshteh Izadi, Mona Zamanian-Azodi, Vahid Mansouri, Mahsa Khodadoostan, Nosratollah Naderi
Aim: The main goal of this analysis was prioritization of co-expressed genes and miRNAs that are thought to have important influences in the pathogenesis of colon and lung cancers. Background: MicroRNAs (miRNAs) as small and endogenous noncoding RNAs which regulate gene expression by repressing mRNA translation or decreasing stability of mRNAs; they have proven pivotal roles in different types of cancers. Accumulating evidence indicates the role of miRNAs in a wide range of biological processes from oncogenesis and tumor suppressors to contribution to tumor progression...
2017: Gastroenterology and Hepatology From Bed to Bench
Karen M Funderburk, Scott S Auerbach, Pierre R Bushel
Chemicals, toxicants, and environmental stressors mediate their biologic effect through specific modes of action (MOAs). These encompass key molecular events that lead to changes in the expression of genes within regulatory pathways. Elucidating shared biologic processes and overlapping gene networks will help to better understand the toxicologic effects on biological systems. In this study we used a weighted network analysis of gene expression data from the livers of male Sprague-Dawley rats exposed to chemicals that elicit their effects through receptor-mediated MOAs (aryl hydrocarbon receptor, orphan nuclear hormone receptor, or peroxisome proliferator-activated receptor-α) or non-receptor-mediated MOAs (cytotoxicity or DNA damage)...
2017: Frontiers in Genetics
Alexey V Ulasov, Andrey A Rosenkranz, Alexander S Sobolev
Transcription factors (TFs) are at the center of the broad regulatory network orchestrating gene expression programs that elicit different biological responses. For a long time, TFs have been considered as potent drug targets due to their implications in the pathogenesis of a variety of diseases. At the same time, TFs, located at convergence points of cellular regulatory pathways, are powerful tools providing opportunities both for cell type change and for managing the state of cells. This task formulation requires the TF modulation problem to come to the fore...
November 4, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Bin Yu, Jia-Meng Xu, Shan Li, Cheng Chen, Rui-Xin Chen, Lei Wang, Yan Zhang, Ming-Hui Wang
Gene regulatory networks (GRNs) research reveals complex life phenomena from the perspective of gene interaction, which is an important research field in systems biology. Traditional Bayesian networks have a high computational complexity, and the network structure scoring model has a single feature. Information-based approaches cannot identify the direction of regulation. In order to make up for the shortcomings of the above methods, this paper presents a novel hybrid learning method (DBNCS) based on dynamic Bayesian network (DBN) to construct the multiple time-delayed GRNs for the first time, combining the comprehensive score (CS) with the DBN model...
October 6, 2017: Oncotarget
Kaimin Guo, Zuowen Liang, Fubiao Li, Hongliang Wang
The present study aimed to identify the regulatory mechanisms associated with the metastasis of prostate cancer (PC). The microRNA (miRNA/miR) microarray dataset GSE21036 and gene transcript dataset GSE21034 were downloaded from the Gene Expression Omnibus database. Following pre-processing, differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) between samples from patients with primary prostate cancer (PPC) and metastatic prostate cancer (MPC) with |log2 fold change (FC)| >1 and a false discovery rate <0...
November 2017: Oncology Letters
Esterina D'Asti, G Mark Anderson, Janusz Rak
Tissue factor (TF) is a transmembrane receptor for coagulation factor VII/VIIa that is frequently overexpressed by cancer cells. The TF/VIIa complex acts as the main initiator of the clotting cascade in blood and a trigger of intracellular signaling that changes gene expression and the cellular phenotype. However, pathways mediating these changes are still poorly characterized and especially the impact of TF signals on regulatory microRNA (miR) networks in cancer remains unknown. We show that the monoclonal antibody that selectively neutralises the signaling (but not coagulant) function of human TF (CNTO 2559) inhibits progression of MDA-MB-231 breast cancer xenografts in mice and prolongs animal survival...
October 27, 2017: Biochemical and Biophysical Research Communications
Trevor L Davis, Charlene S L Hoi, Ilaria Rebay
A limited collection of signaling networks and transcriptional effectors directs the full spectrum of cellular behaviors that comprise development. One mechanism to diversify regulatory potential is to combine multiple biochemical activities into the same protein. Exemplifying this principle of modularity, Eyes absent (Eya), originally identified as a transcriptional co-activator within the retinal determination gene network (RDGN), also harbors tyrosine and threonine phosphatase activities. Although mounting evidence argues for the importance of Eya's phosphatase activities to mammalian biology, genetic rescue experiments in Drosophila have shown that the tyrosine phosphatase function is dispensable for normal development...
2017: PloS One
Chao Xue, Shuai Liu, Chen Chen, Jun Zhu, Xibin Yang, Yong Zhou, Rui Guo, Xiaoyu Liu, Zhiyun Gong
Lysine acetylation (Kac) is an important protein post-translational modification in both eukaryotes and prokaryotes. Herein, we report the results of a global proteome analysis of lysine acetylation and its diverse functions in rice (Oryza sativa). We identified 1353 Kac sites in 866 proteins in rice seedlings. A total of 11 Kac motifs are conserved, and 45% of the identified proteins are localised to the chloroplast. Among all acetylated proteins, 38 Kac sites are combined in core histones. Bioinformatics analysis revealed that Kac occurs on a diverse range of proteins involved in a wide variety of biological processes, especially photosynthesis...
November 6, 2017: Proteomics
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