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biological regulatory network

Caleb J Bashor, James J Collins
Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function...
March 16, 2018: Annual Review of Biophysics
Ximena Corso-Díaz, Catherine Jaeger, Vijender Chaitankar, Anand Swaroop
Complex biological processes, such as organogenesis and homeostasis, are stringently regulated by genetic programs that are fine-tuned by epigenetic factors to establish cell fates and/or to respond to the microenvironment. Gene regulatory networks that guide cell differentiation and function are modulated and stabilized by modifications to DNA, RNA and proteins. In this review, we focus on two key epigenetic changes - DNA methylation and histone modifications - and discuss their contribution to retinal development, aging and disease, especially in the context of age-related macular degeneration (AMD) and diabetic retinopathy...
March 12, 2018: Progress in Retinal and Eye Research
JoAnne S Richards
Follicular development and ovulation are complex development processes that are regulated by multiple, interacting pathways and cell types. The oocyte, cumulus cells, granulosa cells, and theca cells communicate to impact follicular development and ovulation. Many hormones and cytokines control intracellular regulatory networks and transcription factors, some of which are cell type specific. Molecular biology approaches and mutant mouse models have contributed immensely to our knowledge of what genes and signaling cascades impact each stage of follicular development and ovulation, and how the alteration of gene expression profiles and the activation of specific signaling pathways can impact ovarian cancer development in ovarian surface epithelial cells as well as granulosa cells...
2018: Vitamins and Hormones
Jinxu Gao, Adelphe Mfuh, Yuka Amako, Christina M Woo
Many therapeutics elicit cell-type specific polypharmacology that is executed by a network of molecular recognition events between a small molecule and the whole proteome. However, measurement of the structures that underpin the molecular associations between the proteome and even common therapeutics, such as the nonsteroidal anti-inflammatory drugs (NSAIDs), is limited by the inability to map the small molecule interactome. To address this gap, we developed a platform termed small molecule interactome mapping by photoaffinity labeling (SIM-PAL) and applied it to the in cellulo direct characterization of specific NSAID binding sites...
March 15, 2018: Journal of the American Chemical Society
Julie E Maguire, Aakarsha Pandey, Yushi Wu, Anna Di Gregorio
Ascidian embryos have been employed as model systems for studies of developmental biology for well over a century, owing to their desirable blend of experimental advantages, which include their rapid development, traceable cell lineage, and evolutionarily conserved morphogenetic movements. Two decades ago, the development of a streamlined electroporation method drastically reduced the time and cost of transgenic experiments, and, along with the elucidation of the complete genomic sequences of several ascidian species, propelled these simple chordates to the forefront of the model organisms available for studies of regulation of gene expression...
2018: Advances in Experimental Medicine and Biology
Tiandong Che, Diyan Li, Long Jin, Yuhua Fu, Yingkai Liu, Pengliang Liu, Yixin Wang, Qianzi Tang, Jideng Ma, Xun Wang, Anan Jiang, Xuewei Li, Mingzhou Li
Genome-wide transcriptomic studies in humans and mice have become extensive and mature. However, a comprehensive and systematic understanding of protein-coding genes and long non-coding RNAs (lncRNAs) expressed during pig spleen development has not been achieved. LncRNAs are known to participate in regulatory networks for an array of biological processes. Here, we constructed 18 RNA libraries from developing fetal pig spleen (55 days before birth), postnatal pig spleens (0, 30, 180 days and 2 years after birth), and the samples from the 2-year-old Wild Boar...
2018: PloS One
Jun Ding, James S Hagood, Namasivayam Ambalavanan, Naftali Kaminski, Ziv Bar-Joseph
The Dynamic Regulatory Events Miner (DREM) software reconstructs dynamic regulatory networks by integrating static protein-DNA interaction data with time series gene expression data. In recent years, several additional types of high-throughput time series data have been profiled when studying biological processes including time series miRNA expression, proteomics, epigenomics and single cell RNA-Seq. Combining all available time series and static datasets in a unified model remains an important challenge and goal...
March 14, 2018: PLoS Computational Biology
Kumar Parijat Tripathi, Marina Piccirillo, Mario Rosario Guarracino
BACKGROUND: The endomembrane system, known as secretory pathway, is responsible for the synthesis and transport of protein molecules in cells. Therefore, genes involved in the secretory pathway are essential for the cellular development and function. Recent scientific investigations show that ER and Golgi apparatus may provide a convenient drug target for cancer therapy. On the other hand, it is known that abundantly expressed genes in different cellular organelles share interconnected pathways and co-regulate each other activities...
March 8, 2018: BMC Bioinformatics
Guangyong Zheng, Tao Huang
In post-genomic era, an important task is to explore the function of individual biological molecules (i.e., gene, noncoding RNA, protein, metabolite) and their organization in living cells. For this end, gene regulatory networks (GRNs) are constructed to show relationship between biological molecules, in which the vertices of network denote biological molecules and the edges of network present connection between nodes (Strogatz, Nature 410:268-276, 2001; Bray, Science 301:1864-1865, 2003). Biologists can understand not only the function of biological molecules but also the organization of components of living cells through interpreting the GRNs, since a gene regulatory network is a comprehensively physiological map of living cells and reflects influence of genetic and epigenetic factors (Strogatz, Nature 410:268-276, 2001; Bray, Science 301:1864-1865, 2003)...
2018: Methods in Molecular Biology
Mariia Rabyk, Oleksandr Yushchuk, Ihor Rokytskyy, Maria Anisimova, Bohdan Ostash
The AdpA protein from a streptomycin producer Streptomyces griseus is a founding member of the AdpA family of pleiotropic regulators, known to be ubiquitously present in streptomycetes. Functional genomic approaches revealed a huge number of AdpA targets, leading to the claim that the AdpA regulon is the largest one in bacteria. The expression of adpA is limited at the level of translation of the rare leucyl UUA codon. All known properties of AdpA regulators were discovered on a few streptomycete strains. There are open questions about the true abundance and diversity of AdpA across actinobacterial taxa (and beyond) and about the possible evolutionary forces that shape the AdpA orthologous group in Streptomyces...
March 13, 2018: Journal of Molecular Evolution
Dong-Wook Kim, Keun-Cheol Kim, Kee-Beom Kim, Colin T Dunn, Kwon-Sik Park
The discovery of recurrent alterations in genes encoding transcription regulators and chromatin modifiers is one of the most important recent developments in the study of the small cell lung cancer (SCLC) genome. With advances in models and analytical methods, the field of SCLC biology has seen remarkable progress in understanding the deregulated transcription networks linked to the tumor development and malignant progression. This review will discuss recent discoveries on the roles of RB and P53 family of tumor suppressors and MYC family of oncogenes in tumor initiation and development...
February 2018: Translational Lung Cancer Research
Guangde Zhang, Haoran Sun, Yawei Zhang, Hengqiang Zhao, Wenjing Fan, Jianfei Li, Yingli Lv, Qiong Song, Jiayao Li, Mingyu Zhang, Hongbo Shi
Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play important roles in initiation and development of human diseases. However, the mechanism of ceRNA regulated by lncRNA in myocardial infarction (MI) remained unclear. In this study, we performed a multi-step computational method to construct dysregulated lncRNA-mRNA networks for MI occurrence (DLMN_MI_OC) and recurrence (DLMN_MI_Re) based on "ceRNA hypothesis". We systematically integrated lncRNA and mRNA expression profiles and miRNA-target regulatory interactions...
December 2018: Cell Death Discovery
Jonathan P Rehfuss, Kenneth M DeSart, Jared M Rozowsky, Kerri A O'Malley, Lyle L Moldawer, Henry V Baker, Yaqun Wang, Rongling Wu, Peter R Nelson, Scott A Berceli
BACKGROUND: Despite being the definitive treatment for lower extremity peripheral arterial disease, vein bypass grafts fail in half of all cases. Early repair mechanisms after implantation, governed largely by the immune environment, contribute significantly to long-term outcomes. The current study investigates the early response patterns of circulating monocytes as a determinant of graft outcome. METHODS: In 48 patients undergoing infrainguinal vein bypass grafting, the transcriptomes of circulating monocytes were analyzed preoperatively and at 1, 7, and 28 days post-operation...
March 2018: Circ Genom Precis Med
Silvia Parolo, Luca Marchetti, Mario Lauria, Karla Misselbeck, Marie-Pier Scott-Boyer, Laura Caberlotto, Corrado Priami
Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways...
2018: PloS One
Tong Hao, Dan Wu, Lingxuan Zhao, Qian Wang, Edwin Wang, Jinsheng Sun
The genome-scale cellular network has become a necessary tool in the systematic analysis of microbes. In a cell, there are several layers (i.e., types) of the molecular networks, for example, genome-scale metabolic network (GMN), transcriptional regulatory network (TRN), and signal transduction network (STN). It has been realized that the limitation and inaccuracy of the prediction exist just using only a single-layer network. Therefore, the integrated network constructed based on the networks of the three types attracts more interests...
2018: Frontiers in Microbiology
Yujia Zhao, Jingjing Fan, Chen Wang, Xudong Feng, Chun Li
Oleanolic acid is a plant-derived pentacyclic triterpenoid compound with various biological activities. Recently, biosynthesis of oleanolic acid in microbes has been demonstrated as a promising and green way, but the production is too low for industrialization. To improve oleanolic acid production, this study constructed a novel pathway for biosynthesis of oleanolic acid in Saccharomyces cerevisiae by improving the pairing efficiency between cytochrome P450 monooxygenase and reductase. Furthermore, to improve the transcriptional efficiency of heterologous genes, the cellular galactose regulatory network was reconstructed by knocking out galactose metabolic genes GAL80 and GAL1...
February 23, 2018: Bioresource Technology
Sarada Achyutuni, Revathy Nadhan, Satheesh Kumar Sengodan, Priya Srinivas
Chromosome 17 (Chr17) harbors crucial genes that encode proteins implicated in a variety of cancers, including some that guard cancer cells from genomic instability and others that interfere with metastasis. Included amongst the genes on chr17 that regulate biological processes fundamental to the genesis of cancer are TP53, BRCA1, CCL5, NF-1, and GRB7. As many as 50% of all human tumors and at least 30% of breast carcinomas contain p53 mutations, while 30%-40% of breast cancers have defective BRCA1. A large number of proteins regulate the expression of these cancer genes on chr17 with miRNAs, the most widely studied class of regulatory RNAs, playing a major role in epigenetically controlling the gene expression programs, thereby managing various cellular functions...
August 2017: Seminars in Oncology
Magdalini Sachana, Alexandra Rolaki, Anna Bal-Price
The Adverse Outcome Pathways (AOPs) are designed to provide mechanistic understanding of complex biological systems and pathways of toxicity that result in adverse outcomes (AOs) relevant to regulatory endpoints. AOP concept captures in a structured way the causal relationships resulting from initial chemical interaction with biological target(s) (molecular initiating event) to an AO manifested in individual organisms and/or populations through a sequential series of key events (KEs), which are cellular, anatomical and/or functional changes in biological processes...
March 7, 2018: Toxicology and Applied Pharmacology
Jialei Ji, Limei Yang, Zhiyuan Fang, Mu Zhuang, Yangyong Zhang, Honghao Lv, Yumei Liu, Zhansheng Li
Plant male reproductive development is a very complex biological process that involves multiple metabolic pathways. To reveal novel insights into male reproductive development, we conducted an integrated profiling of gene activity in the developing buds of a cabbage recessive genetic male sterile mutant. Using RNA-Seq and label-free quantitative proteomics, 2881 transcripts and 1245 protein species were identified with significant differential abundance between the male sterile line 83121A and its isogenic maintainer line 83121B...
March 6, 2018: Journal of Proteomics
Marc Lenoir, Cansel Ustunel, Sandya Rajesh, Jaswant Kaur, Dimitri Moreau, Jean Gruenberg, Michael Overduin
Sorting nexins anchor trafficking machines to membranes by binding phospholipids. The paradigm of the superfamily is sorting nexin 3 (SNX3), which localizes to early endosomes by recognizing phosphatidylinositol 3-phosphate (PI3P) to initiate retromer-mediated segregation of cargoes to the trans-Golgi network (TGN). Here we report the solution structure of full length human SNX3, and show that PI3P recognition is accompanied by bilayer insertion of a proximal loop in its extended Phox homology (PX) domain. Phosphoinositide (PIP) binding is completely blocked by cancer-linked phosphorylation of a conserved serine beside the stereospecific PI3P pocket...
March 8, 2018: Nature Communications
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